Free Exhibit to a Document - District Court of Delaware - Delaware

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Exhibit A

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I IIIII II111111 III IIIII IIIII IIIII IIIII IIIII IIIII II111 III
US006576666B2

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(12) United States Patent
Hermelin et al.

(10) Patent No.: US 6,576,666 B2 (45) Date of Patent: Jun. 10, 2003

(54) (75)

NUTRITIONAL SUPPLEMENTS Inventors: Marc S. Hermelin, Glendale, MO (US); R. Saul Levinson, Chasterfield, MO (US); George Paradissis, St. Louis, MO (US)

5,635,198 A 5,744,161 A 5,776,504 A

6/1997 Nishimura et al .......... 4/1998 Majeed et al ............... 7/1998 McCarty ..................... OTHER PUBLICATIONS

424/438 424/464 424/682

(73) Assignee: Drugtech Corporation, Wilmington, DE (US) (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.

(21) (22) (65)

Appl. No.: 09/885,158 Filed: Jun. 21, 200~. Prior Publication Data US 2002/0032234 A1 Mar. 14, 2002 Related U.S. Application Data

(63) (51) (52) (58) (56)

Continuation of application No. 09/323,159, filed on Jun. 1, 1999, now Pat. No. 6,258,846. Int. C].7 ........................ A61K 31/20; A61K 31/44; A61K 31/495; A61K 31/50; A61K 31/34 U.S. CI ........................ 514/560; 514/345; 514/249; 514/474; 514/458 Field nf Search ................................. 514/560, 345, 514/249, 474, 458 References Cited U.S. PATENT DOCUMENTS 3,925,560 A 4,642,317 A 4,753,926 A 5,004,728 A 5,143,737 A 5,264,217 A 5,562,913 A 12/1975 Scott et al ..................... 426/2 2/1987 Palmquist et al ........... 514/588 6/1988 Lucas et al .................... 514/2 4/1991 Chalupa et al ................ 514/12 9/1992 Richardson .................... 426/2 11/1993 Horrobin .................... 424/439 10/1996 Horrobin .................... 424/401

Clark et al, 117CA:25288, 1992.* FDA (United States Food and Drag Administration), 104CA:4736, 1985.* Alvarez et al. 107CA:22135, 1986.* The Merck Manual 185:968 (16'h Ed. 1992). The Merck Manual 185:1929-1931 (16'h Ed. 1992). Physician Desk Reference (PDR), 53ra Ed., 1011, 1999. Physician Desk Reference (PDR), 53"a Ed., 1522-3, 1999. Physician Desk Reference (PDR), 53ra Ed., 1692, 1999. Physician Desk Reference (PDR), 53ra Ed., 2802, 1999. Physician Desk Reference (PDR), 53~a Ed., 2916-17, 1999. Physician Desk Reference (PDR), 53ra Ed., 2917-18, 1999. Physician Desk Reference (PDR), 53ra Ed., 3128, 1999. Physician Desk Reference (PDR), 53ra Ed., 3163, 1999. Physician Desk Reference (PDR), 53ra Ed., 3212, 1999. Whitney, E. and Rolfes, S., Understanding Nutrition, 6'h Ed., 136-40, 1993. Whitney, E. and Rolfes, S., Understanding Nutrition, 6'h Ed., 493-504, 1993. * cited by examiner Primary Examiner---Russell Travers (74) Attorney, Agent, or Firm---Nath & Associates PLLC; Gary M. Nath (57) ABSTRACT

The present disclosure relates to novel nutritional compositions containing linoleic acid and/or linolenic acid which optimize child neurological development and provide improved nutritional support for women prior to and during lactation. The nutritional compositions are intended for use by women to optimize infant neurological development and provide improved nutritional support for women prior to, during and after lactation. 23 Claims, No Drawings

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The presence of fatty acids in breast milk is significant for various reasons, as described below. First, the body derives most of its energy from triglycerides, a molecule of glycerol This application is a continuation application of U.S. patent application Set. No. 09/323,159, filed Jun. 1, 1999 with three fatty acids attached. The stored fatty acids support now U.S. Pat. No. 6,258,846, the entire contents of which 5 most of life's activities when individual's are between meals are hereby incorporated by reference in their entirety. or must go without food. While the body can make many fatty acids, it cannot make linoleic acid or linolenic acid. BACKGROUND OF THE INVENTION These two fatty acids are indispensable to body functions and therefore must be supplied through food. 1. Field of the Invention Secondly, essential fatty acids are important for the develThe present invention is directed to novel compositions 10 containing fatty acids, in particular, linoleic acid and lino- oping brain, immunological system and cardiovascular system, and have some role to play in every organ of the lenic acid, for use by pregnant and/or lactating women to body. Linoleic acid is the most important member of the optimize infant neurological development and provide omega-6 family of fatty acids. The body uses linoleic acid to improved nutritional support for women prior to, during and 15 synthesize an important 20-carbon fatty acid, arachidonic after lactation. acid, which helps maintain the structural integrity of cell 2. Description of the Related Art membranes. At some time prior to the end of pregnancy, pregnant Linolenic acid is the most important member of the women face the decision of whether or not to breast-feed their infants. It is estimated that over 50% of all mothers 20 omega-3 family of fatty acids. The body requires this fatty acid to make eicosapentaenoic acid (EPA) and docosachoose to breast-feed their infants. See The Merck Manual, hexaenoic acid (DI-IA). Many body tissues require EPA and 185:1929-1931 (1.6th ed. 1992). Furthermore, the number of DHA. DHA is especially important in the retina and in the women deciding to breast-feed appears to be on the increase, cerebral cortex of the brain. Half of the DHA in a fetus's particularly in higher socioeconomic groups. Id. Most experts would agree that this increase is very desirable in 25 body accumulates in the brain before birth, and half after birth, an indication of the importance of fatty acids to the view of the numerous recognized nutritional benefits for fetus during pregnancy and then to the young infant during developing infants which accompany their consumption of lactation. human milk. Because of the nutritional benefits for infants, Successful breast-feeding requires that the mother mainmany health care providers and dietitians believe breastfeeding is sufficiently important to warrant that every effort 3o !ain good nutrition and adequate rest. Agood, nutritional diet ~s needed to support the stamina that nursing an infant be made to breast-feed, even if only for a short time. See requires. Beyond this, however, a woman must consume a Whitney et al., Understanding Nutrition, 493-504 (6'h ed. nutrient-rich diet to produce nutrient-rich milk. 1993). A healthy nursing mother generally makes about 25 Moreover, in addition to the nutritional benefits of breastfeeding, many women simply want to breast-feed their 35 ounces of milk each day. To produce this milk, the mother needs to consume 650 kcalofies above what she would infants for emotional or psychological reasons. However, normally require for herself. Woman are advised to eat about regardless of a women's underlying reasons for breast500 kcalories worth of extra food and let the extra fat left feeding, her nutritional status is implicated in the decision of over from pregnancy provide the rest. Woman may not whether to breast-feed her child. For example, a nutritional deficiency in a woman may severely limit the quantity of 40 consume enough food for many reasons, including the desire to lose all of the weight gained during pregnancy. But breast milk which is produced or, in some cases, entirely restricting food and energy in this fashion will result in prevent lactation from occurring. breast milk which is lacking in nutrients, low quantities of Generally speaking, the nutritional benefits of breastbreast milk or, in the worse case scenario, no breast milk at feeding stem from the unique nutrient composition and protective factors present in breast milk which promote 45 all. According to the medical literature, a nursing mother infant health and development. Id. at 494. For example, should eat foods high in nutrients and drink plenty of fluid. breast milk generally contains all of the vitamins required Nutritional deprivation in the mother generally reduces the for infant development, with the possible exception of quantity, more so than the quality, of the milk. So while vitamin D. Id. at 500. Further, breast milk is an abundant source of minerals and, more importantly, some minerals are s0 woman can produce milk with sufficient protein, carbohydrate, fat and minerals even if their own intake is present in breast milk in highly desirable ratios (e.g., the insufficient, the quality of the breast milk is maintained at the 2-to-1 ratio of calcium to phosphorus in breast milk is ideal expense of the mother's own nutrient repositories. for the absorption of calcium), ld. Breast milk also contains invaluable immunological agents, including antiviral agents Moreover, quantities of particular vitamins, such as B 6, B 12, such as immunoglobulins, and antibacterial agents such as 55 A and D, in breast milk will actually decline in response to a inadequate intakes by the mother. lactoferrin. Infants have different nutritional needs than those of In addition to the above discussed vitamins, minerals and immunological agents, breast milk also contains various children and adults. They require more fat and less protein than adults. Breast milk contains high concentrations of "energy nutrients". For example, breast milk contains lactose which is the carbohydrate present in breast milk and 60 fat-digesting enzymes that allow for highly efficient fat absorption. Breast milk, as well as colostrum, contain the which facilitates calcium absorption. Id. A relatively small essential fatty acid linoleic acid. Understanding Nutrition, amount of protein, primarily in the form of alphaWhitney and Rolfe, 6'h Ed., 136-40 (1993). lactalbumin, is also present in breast milk, thus placing less stress on the infant's immature kidneys. Id. Breast milk Full term babies who are not fed enough linoleic acid additionally contains fat along with fat-digesting enzymes. 65 suffer from dermatosis and growth failure. These conditions Id. Linoleic acid, a fatty acid, is found in large quantities in are easily reversed when linoleic acid is added to the infant's diet. Fatty acid deficiency in a breast-feeding infant is a breast milk. Id.

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hazzard of long term low fat parental dieting. The Merck mg of niacinamide, 12 mcg of vitamin Baz, 30 mcg of biotin, 10 mg of pantothenic acid, 200 mg of calcium, 150 mcg of Manual, 16'h Ed., 968 (1992). iodine, 27 mg of iron, 25 mg of magnesium, 2 mg of copper, Methods of administering linolenic acid to lactating 25 mg of zinc, 25 mg of chromium, 25 mg of molybdenum, females have been previously described. Specifically, Horrobin, U.S. Pat. No. 5,264,217, discloses methods for 5 5 mg of manganese, and 20 mcg of selenium per dose. Materna® is designed "provide vitamin and minerals increasing the total fat content of milk, the essential fatty supplementation prior to conception, throughout pregnancy acid content of milk and the flow of milk during lactation, or for preventing or reducing the normal decrease in milk fat and during the postnatal period for both lactating and nonlactating mothers" and is available in tablet form only. content that occurs during prolonged lactation, by adminisSee. ld. at 1522-3. tering gamma linolenic acid, dihomo-gamma-linolenic acid Enfamil® Natalins® RX multivitamin and multimineral or their mixture to a lactating female. supplements, available from Mead Johnson Nutritionals, Other references disclose compositions and methods that Evansville, Ind., provide 4000 I.U. of vitamin A, 80 mg of have been developed for achieving fat enrichment of rumi- vitamin C, 400 I.U. of vitamin D, 15 I.U. of vitamin E, 1.5 nant milk for consumption by humans. In general, animal mg of thiamin, 1.6 mg of riboflavin, 17 mg niacin, 4 mg of feed is supplemented with fatty acids. In tum, the milk 15 vitamin Br, 1 mg of folic acid, 2.5 mcg of vitamin Boa, 30 produced by the ruminants is itself rich in fatty acids. meg of biotin, 7 mg of pantothentic acid, 200 mg of calcium, ChaIupa et al., U.S. Pat. No. 5,004,728, describe a method 54 mg of iron, 25 mg of zinc, and 3 mg of copper per dose. for increasing milk yields in lactating ruminants. The rumiEnfamil® Natalins® RX are "to supplement the diet during nants are fed somatotropin and salts of long chain fatty pregnancy of lactation" and are available only in tablet form. acids. The fatty acids in the feed increases the level of long 20 See Id. at 1692. chain fatty acids in the milk produced by the ruminant. One Prenate® UltraTM prenatal vitamins, available from long chain fatty acid suitable for this inventive subject Sanofi Pharmaceuticals, New York, N.Y., contain 90 mg of matter is linoleic acid. elemental iron, 150 meg of iodine, 200 mg of calcium, 2 mg Nishimura et al., U.S. Pat. No. 5,635,198, describe a 25 of copper, 25 mg of zinc, 1 mg of folio acid, 2700 I.U. of granular agent comprised by an active core coated by certain vitamin A, 400 I.U. of vitamin Do, 30 I.U. of vitamin E, 120 fatty acids and oils to be administered to ruminants. This mg of vitamin C, 3 mg of vitamin B~, 304 mg of vitamin Be, granular agent has a superior absorption rate and results in, 20 mg of vitamin B6, 12 mcg of vitamin Blz, 20 mg of among other benefits, efficient lactation in the ruminant. niacinamide, and 50 mg of docusate sodium per dose. Scott etal., U.S. Pat. No. 3,925,560, describe a feed 3o Prenate® UltraTM is "indicated for use in improving the supplement for ruminants comprising fatty acids encapsunutritional status of women throughout pregnancy and in the lated with a protein-aldehyde reaction product. These fatty postnatal period for both lactating and nonlactating mothers acid supplements, including linoleic acid, provide high and is only available in tablet form. See Id. at 2802. energy feed supplements for ruminants. These supplements Nifemx®-PN formula, available from Schwarz Pharma, will result in the ruminate producing a milk very high in 35 Inc., Milwaukee, Wis., contains 60 mg of iron, i mg of folic unsaturated fats. acid, 50 mg of vitamin C, 3 mcg of vitamin Baa, 4,000 I.U. Palmquist et ai., U.S. Pat. No. 4,642,317, describe a of vitamin A, 400 I.U. of vitamin D, 2.43 mg of vitamin B~, process for feeding ruminants fatty acids in the form of their 3 mg of vitamin B2, 1.64 mg of vitamin Ba, 10 mg of calcium salts, which are added to feed. This process would niacinamide, 125 mg of calcium, and 18 mg of zinc per dose. allow dairy cows to make milk high in fats, without deplet- 4o Niferex®-PN is "indicated for prevention and/or treatment ing their own fatty acid stores. of dietary vitamin and mineral deficiencies associated with pregnancy and lactation" and is only available in tablet form. Richardson, U.S. Pat. No. 5,143,737, describes a method for the modification of ruminant food so that the ruminant See Physicians" Desk Reference, (53d Ed., 1999) 2916-7. will produce a milk with modified fat. This method comNiferex®-PN Forte formula, available from Schwarz prises a non-toxic food to be surrounded by an acid-sensitive 45 Pharma, Inc., Milwaukee, Wis., contains 60 mg of iron, 1 mg nontoxic crosslinking material. Animals eating this compo- of folic acid, 50 mg of vitamin C, 3 mcg of vitamin B~z, sition will make milk with a higher level of unsaturated fats. 5,000 I.U. of vitamin A, 400 I.U. of vitamin D, 30 I.U. of Furthermore, several prenatal supplements are available vitamin E, 80 mg of vitamin C, i mg of folic acid, 3 mg of which provide pregnant women with varying amounts of vitamin B1, 3.4 mg of vitamin B2, 4 mg of vitamin Br, 20 vitamins and minerals. The Physicians' Desk Reference50 mg of niacinamide, 12 mcg of vitamin B:t2, 250 mg of describes various vitamin and mineral supplements for use calcium, 200 mcg of iodine, 10 mg of magnesium, 2 mg of by pregnant women. For example, Nestabs® CBF, prenatal copper, and 25 mg of zinc per dose. Niferex®-PN is "inditbrmula, available from The Fielding Company, Maryland cated for prevention and/or treatment of dietary vitamin and Heights, Mo., contains 4,000 I.U. of vitamin A, 400 I.U. of mineral deficiencies associated with pregnancy and lactavitamin D, 30 I.U. of vitamin E, 120 mg of vitamin C, 1 mg 55 tion" and is only available in tablet form. See Id. at 2917-8. of folic acid, 3 mg of thiamine, 3 mg of riboflavin, 20 mg of Advanced Formula Zenate® prenatal multivitamin/ niacinamide, 3 mg of pyridoxine, 8 mcg of vitamin B12, 20 mineral supplement, available from Solvay mg of calcium, 100 mcg of iodine, 15 mg of zinc, and 50 mg Pharmaceuticals, Marietta, Ga., contains 3,000 I.U. of vitaof iron per dose. NESTABS® CBF are "expressly formumin A, 400 I.U. of vitamin D, 10 I.U. of vitamin E, 70 mg lated for use during pregnancy and lactation" and are 60 of vitamin C, 1 mg of folic acid, 1.5 mg of vitamin B~, 1.6 available only in tablet form. See Physicians' Desk mg of vitamin B2, 17 mg of niacin, 2.2 mg of vitamin B~, 2.2 Reference, (53d Ed., 1999) 1011. of vitamin B~2, 200 mg of calcium, 175 mcg of iodine, 65 Materna® prenatal vitamin and mineral formula, availmg of iron, 100 mg of magnesium, and 15 mg of zinc per able from Lederle Laboratories, Pearl River, N.Y., contains dose. Advanced Formula Zenate® is "a dietary adjunct in 5,000 I.U. of vitamin A, 400 I.U. of vitamin D, 30 I.U. of 65 nutritional stress associated with periconception, pregnancy vitamin E, 120 mg of vitamin C, 1 mg of folio acid, 3 mg of and lactation" and is only available in tablet form. See Id. at vitamin B1, 3.4 mg of vitamin B2, 10 mg of vitamin B6, 20 3128.

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Precare® prenatal multi-vitamin/mineral formula, avail- derivative thereof and a combination thereof in an amount able from UCB Pharma, Inc., Smyrna, Ga., contains 50 mg ranging from 10 mg to 100 rag; a second fatty acid cornof vitamin C, 250 mg of calcium, 40 mg of iron, 6 meg of pound selected from the group consisting of a docosavitamin D, 3.5 mg of vitamin E, 2 mg of vitamin Be, 1 mg hexaenoie acid compound, an omega-3 fatty acid, and of folio acid, 50 mg of magnesium, 15 mg of zinc and 2 mg5 omega-2 fatty acid, a derivative thereof and a combination thereof in an amount ranging from about 10 mg to 100 rag; of copper per dose. Precare® "is indicated to provide a vitamin B6 compound or derivative thereof in a range of vitamin and mineral supplementation throughout pregnancy about 20 mg to 125 mg; a folio acid compound or derivative and during the postnatel period for both lactating and thereof in a range of about 0.1 mg to 3 rag; and a calcium nonlactating mothers and is available only in caplet form. See Id. at 3163. ~0 compound or derivative thereof in a range of about 100 mg to 1000 mg. The weight ratio of the first fatty add compound Natafort® prenatal multivitamin, available from Warner to the second fatty acid compound is about 1:0.1 to 10. Chilcott, Rockaway, N.J., contains 1,000 I.U. pf vitamin A, In a further embodiment of the inventive subject matter, 400 I.U. of vitamin D3, 11 I.U. of vitamin E, 120 mg of a composition comprises a first fatty add compound selected vitamin C, 1 mg of folio acid, 2 mg of thiamine mononitrate, from the group consisting of linoleie acid, linolenic acid, a 3 mg of riboflavin, 20 mg of niacinamide, 10 mg of vitamin 15 derivative thereof and a combination thereof in an amount B~, 12 meg of vitamin B12, and 60 mg of iron per dose. ranging from 10 mg to 100 rag; a second fatty acid comNatafort® is designed "to provide vitamin and mineral pound selected from the group consisting of a docosasupplementation throughout pregnancy and during the posthexaenoic acid compound, an omega-3 fatty acid, and natal period, for both the lactating and non-lactating mother" 20 omega-2 fatty acid, a derivative thereof and a combination and is only available in tablet form. See ld. at 3212. thereof in an amount ranging from about 10 mg to 100 rag; However, none of the above formulations provide women a vitamin B6 compound or derivative thereof in a range of with essential fatty acids in amounts and proportions neeabout 20 mg to 125 mg; a folio acid compound or derivative essary to optimize infant neurological development. Further, thereof in a range of about 0.1 mg to 3 mg; a calcium the prenatal nutritional supplements containing vitamins and compound a derivative compound or derivative thereof in 25 to 1000 mg;or magnesiumthereof in a range of about 100 mg minerals are entirely lacking in essential fatty acids. In the case of the enriched ruminant milk, while this milk may be a range of about 25 mg to 400 mg; a vitamin C compound a good source of fatty acids for adults, ruminant milk is not or derivative thereof in a range of 25 mg to 400 mg; and a recommended for infants because even supplemented forvitamin E compound or derivative thereof in a range of 10 mula cannot match the immunological benefits of breast mg to 400 mg. The weight ratio of the first fatty acid 30 compound in the composition to the second fatty acid milk. Therefore, there remains a need for a nutritional formucompound in the composition is about 1:0.1 to 10. lation which optimizes infant neurological development. It In a further embodiment of the inventive subject matter, is also desirable to have nutritional formulations which a composition for administration to a female mammal for prevent a woman's stores of fatty acids from becoming 35 enriching the milk of said female mammal to optimize depleted during lactation. There is also a particular need for neurological development of a neonate being nursed by the nutritional formulations which provide essential fatty acids female mammal, which comprises about 10 mg to 1000 mg in optimal ratios and amounts, along with required vitamins per 55 kg of said mammal's body weight of a first fatty acid and minerals. Moreover, it is desirable to have formulations compound for each compound selected from the group and methods which prepare a woman's body for the stresses 40 consisting of a linoleic acid compound, a linolenic acid imposed by lactation, compound, a derivative thereof and a combination thereof; about 10 mg to 1000 mg of a second fatty acid compound SUMMARY OF THE INVENTION selected from the group consisting of a docosahexaenoic The compositions of the present inventive subject matter acid compound, an omega-3 fatty acid, an omega-2 fatty overcome the deficiencies of currently-available nutritional 45 acid, a derivative thereof and a combination thereof; and supplements by providing formulations which are specifiwherein the weight ratio of said first fatty acid compound to cally tailored for women during the period prior to and said second fatty acid compound is about 1:0.01 to 10. during lactatinn and which optimize infant neurological In yet another embodiment of the inventive subject development while inhibiting depletion of a nursing mothmatter, a composition for administration to a woman for er's nutritional stores. The present compositions contain a 50 enriching the breast milk of said woman to optimize neunovel combination of fatty acids in critical ratios and rological development of an infant breast-fed by the woman, amounts, optionally in combination with various vitamins which comprises about 10 mg to 1000 mg of a first fatty acid and minerals, compound for each compound selected from the group consisting of a linoleic acid compound, a derivative thereof In one embodiment of the inventive subject matter, a composition comprises a first fatty acid compound selected 55 and a combination thereof; about 10 mg to 1000 mg of a from the group consisting of linoleic acid, linolenic acid, a second fatty acid compound selected from the group consisting of a docosahexaenoic acid compound, an omega-3 derivative thereof and a combination thereof in an amount ranging from about l0 mg to 100 mg; and a second fatty acid fatty acid, an omega-2 fatty acid, a derivative thereof and a compound selected from the group consisting of a docosacombination thereof; and wherein the weight ratio of said hexaenoic acid compound, an omega-3 fatty acid, and60 first fatty acid compound to said second fatty acid compound omega-2 fatty acid, a derivative thereof and a combination is about 1:0.01 to 10. thereof in an amount ranging from about 10 mg to 100 mg; The inventive subject matter also provides a method for wherein the weight ratio of the first fatty acid compound to enriching the breast milk of a woman to optimize neurothe second fatty acid compound is about 1:0.1 to 10. logical development of her breast-fed infant, which cornIn another embodiment of the inventive subject matter, a 65 prises administering a first fatty acid compound to the woman during a period which begins at least at about the composition comprises a first fatty acid compound selected from the group consisting of linoleic acid, linolenic acid, a tenth week of pregnancy. This first fatty acid compound is

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selected from the group consisting of a linoleic acid ing a first fatty acid compound to the woman during a period commencing at least at about the tenth week of pregnancy compound, a linolenic acid compound, a derivative thereof and terminating at the conclusion of breast-feeding, said first and a combination thereof. It also involves administering a second fatty acid compound to said woman during a period fatty acid compound being selected from the group consistwhich begins at least at about the tenth week of pregnancy. sing of a linoleic acid compound, a linolenic acid compound, The second fatty acid is selected from the group consisting a derivative thereof and a combination thereof; administerof docosahexaenoic acid compound, an omega-3 fatty acid, ing a second fatty acid compound to said woman during the and omega-2 fatty acid, a derivative thereof and a combi- period commencing at least at about the tenth week of nation thereof, and said second fatty acid compound being pregnancy and terminating at the conclusion of breastprovided to the woman together with said first fatty acid lo feeding, said second fatty acid compound being selected compound. The weight range of said first fatty acid comfrom the group consisting of a docosahexaenoic acid pound to said second fatty acid compound is about 1:0.1 to compound, an omega-3 fatty acid, and omega-2 fatty acid, 10. a derivative thereof and a combination thereof, and said second fatty acid compound being provided to the woman In another embodiment of the present invention subject matter, a method for enriching the breast milk of a woman is together with said first fatty acid compound; and wherein the weight ratio of said first fatty acid compound to said second wishing to optimize or who is concerned about the neurofatty acid compound is about 1:0.1 to 10. logical development of the infant she breast-feeds comprises administering a first fatty acid compound in a range of about In a further embodiment of the inventive subject matter, 10 mg to 100 mg to the woman during a period which begins a method for enriching the milk of a female mammal to at least at about the tenth week of pregnancy. This first fatty 20 optimize neurological development of a neonate being nursed by the female mammal, which comprises adminisacid compound is selected from the group consisting of a linoleic acid compound, a linolenic acid compound, a tering a first fatty acid compound to the female mammal during a period commencing at least at about the tenth week derivative thereof and a combination thereof. It also h~volves administering a second fatty acid compound to said of gestation, said first fatty acid compound being selected woman during a period which begins at least at about the 25 from the group consisting of a linoleic acid compound, a linolenic acid compound, a derivative thereof and a combitenth week of pregnancy in a range of 10 mg to 100 mg respectively for linoleic and linolenic acids. The second fatty nation thereof; administering a second fatty acid compound to said female mammal during the period commencing at acid is selected from the group consisting of docosahexaenoic acid compound, an omega-3 fatty acid, and least at about the tenth week of gestation, said second fatty omega-2 fatty acid, a derivative thereof and a combination 30 acid compound being selected from the group consisting of thereof, and said second fatty acid compound being proa docosahexaenoic acid compound, an omega-3 fatty acid, vided to the woman together with said first fatty acid and omega-2 fatty acid, a derivative thereof and a combination thereof, and said second fatty acid compound being compound. The weight range of said first fatty acid compound to said second fatty acid compound is about 1:0.1 to provided to the female mammal together with said first fatty 10. 35 acid compound; and wherein the weight ratio of said first fatty acid compound to said second fatty acid compound is In a further embodiment of the inventive subject matter, about 1:0.1 to 10. a method for enriching the breast milk of a woman to optimize the neurological development of the infant she DETAILED DESCRIPTION OF THE breast-feeds comprises administering a first fatty acid comINVENTION pound to the woman during a period which begins at least at 40 As used herein, "nutritional stores" refers to the levels of about the tenth week of pregnancy and ends at the concluvitamins, minerals and other nutrients which will be availsion of breast-feeding or continues on as a nutritional able for use by the mother, developing embryo, fetus and supplement for the mother in a range of 10 mg to 100 rag. newborn infant. This first fatty acid compound is selected from the group consisting of a linoleic acid compound, a linolenic acid45 "Nutritional status" refers to the presence or absence of any nutrient deficiency, or in other words, the extent to compound, a derivative thereof and a combination thereof. which physiological nutrient demands are being satisfied It also involves administering a second fatty acid compound such that deficiency is avoided. to said woman during a period which begins at least at about "Optimize neurological development" refers to attainthe tenth week of pregnancy. The second fatty acid is selected from the group consisting of docosahexaenoic acid 50 merit of the highest degree of neurological development possible through natural processes without the use of any compound, an omega-3 fatty acid, and omega-2 fatty acid, a derivative thereof and a combination thereof, and said unnatural substances or procedures, such as drugs, surgery and the like. second fatty acid compound being provided to the woman "Biologically active substance" refers to any substance or together with said first fatty acid compound. It also involves administering a nutritional compound to said woman during 55 substances comprising a drug, active therapeutic substance, metabolite, medicament, vitamin, or mineral, any substance a period which begins at least at about the tenth week of used for treatment, prevention, diagnosis, cure or mitigation pregnancy. This compound is selected from a group conof disease or illness, any substance which affects anatomical sisting of a vitamin compound, a biologically-acceptable mineral compound, a derivative thereof and a combination structure or physiological function, or any substance which thereof, and said nutritional compound being administered 60 alters the impact of external influences on an animal, or metabolite thereof, and as used herein, encompasses the together with said first and said second fatty acid comterms "active substance", "therapeutic substance", "agent", pounds. The weight range of said first fatty acid compound "active agent", "active therapeutic agent", "drug", to said second fatty acid compound is about 1:0.1 to 10. "medication", "medicine", "medicant", and other such simiIn a further embodiment of the inventive subject matter, a method for enriching the to a female mammal for enriching65 lar terms. "Specific physiological needs" refers to the unique the milk of said female mammal to optimize neurological requirements for certain levels of certain nutrients by one development of the neonate, which comprises: administer-

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class of persons, such as lactating women, pregnant women, etc., as distinguished from other classes. "Biologically-acceptable" refers to being safe for human consumption. "Neonate" refers to the offspring of a female mammal that is nursed by said female mammal and has not yet been weaned. The compositions of the present inventive subject matter provide several specific new and unexpected benefits. First, the formulations ensure that both the mother and her infant or infants are provided with adequate energy during the period of lactation. Secondly, the formulations allow the mother to maintain adequate fatty acid stores for both her own use and for incorporation into her breast milk as her supplies are depleted during lactation. Thirdly, the fatty acids optimize the neurological development of the infant consuming the breast milk. Fourthly, when administered prior to lactation, the present compositions prepare women for the increased physiological demands and stresses to be placed upon their bodies. Finally, the present compositions help women recover from pregnancy and lactation and prepare ~vomen for additional pregnancies and subsequent lactation. Thus, the inventive subject matter provides a composition designed to be administered to a woman for the purpose of both enriching her breast milk for the benefit of her child and also to directly benefit the woman. In fact, in some cases, the formulations may allow a woman to breast-feed her infant where in the absence of taking the present composition breast-feeding would have been either unsafe or outright impossible. Infants consuming the enriched breast milk, as described herein, will experience optimal neurological development. Further, the present composition will help a post-partum woman to recover from her pregnancy and labor quickly and efficiently by providing her with the fatty acids lost in pregnancy and lactation. In addition, the present composition will place a woman in optimal condition for an additional pregnancy and the lactation that will follow by helping her increase her nutritional stores of critical nutritional compounds. The present inventive subject matter is based, in part, on the discovery that when compositions having certain fatty acids, in certain amounts and proportions to one another, are administered to women prior to and during lactation, infants who consume the breast milk of said women will achieve optimized neurological development. In particular, supplementing the mother's diet with certain fatty acids for a period beginning at ten weeks after conception and either ending when lactation ceases or being continued as a supplement will not only optimize the neural development of the breast-feeding infant, but also ensure that the mother has adequate essential fatty acids for her own use. The fatty acid supplement may also further contain vitamins and minerals to confer added health benefits to the infant and mother. In addition to benefitting a breast-feeding human infant, the present invention can also benefit the offspring of nonhuman mammals that are nursed by their mothers. The composition of the present invention could be administered to a mammal in animal feed, pill form, or other appropriate dosage forms t.o such mammals. Without being limited by theory, the present compositions stimulate the production of breast milk which is enriched with essential fatty acids in amounts which optimize infant neurological development. These compositions achieve such enrichment of the breast milk through one or more natural biological pathways. For example, the arachidonic acid

10
cascade may play a significant role in the enrichment of the breast milk. Specifically, in the arachidonic acid cascade, llnoleic acid is converted first to gamma-linolenic acid and then to further metabolites such as dihomo-gamma-linolenic 5 acid and arachidonic acid which are precursors of 1 or 2 series prostaglandin respectively, as shown in the outline below: cls-Linolelc Acid (9,12-octadecad/enolc acid)

10

15

G-LA (gamma-linoleic acid i.e. 6,9,12-octadeeatrienoie acid)

DOLA DGLA 20 ester reserves ~ (dihomo-gamma-Iinolei acid (small) --*----- i.e. 3,11,14 eicosatrienoic acid

1 1

I series endopcroxides

25

1 series PO's

AA (Amchadonic acid, Le. 5,8,11,14-eicosatrienoic acid)

30 The present composition contains at least two fatty acid compounds. The first fatty acid compound is selected from the group consisting of a linoleic acid compound, a linolenic acid compound, derivatives thereof and combinations thereof. The second fatty acid compound is selected from the 35 group consisting of a docosahexaenoic acid compound, an omega-3 fatty acid compound, an omega-2 fatty acid compound, derivatives thereof and combination thereof. Moreover, when the first fatty acid compound is linolenic acid or a derivative thereof and the second fatty acid 40 compound is an omega-3 fatty acid, said omega-3 fatty acid is not linolenic acid or a derivative thereof. It is also preferred that when the first fatty acid compound is linoleic acid or a derivative thereof and the second fatty acid compound is an omega-2 fatty acid, said omega-2 fatty acid 45 is not linoleic acid or a derivative thereof. The two fatty acid compounds are present in the composition in critical proportions to one another. Preferably, the weight ratio of the first fatty acid to the second fatty acid is about 1:0.001 to 50. More preferably, the weight ratio of the 50 first fatty acid compound to the second fatty acid compound is about 1:0.1 to 10. Even more preferably, the weight ratio of the first fatty acid compound to the second fatty acid compound is about 1:0.9 to 2.5. Most preferably, the weight ratio of the first fatty acid compound to the second fatty acid 55 compound is about 1:1 to 2. The fatty acids of the present inventive subject matter may be used as such or as biologically acceptable and physiologically equivalent derivatives as, for example, detailed later herein. Reference to any of the fatty acids 60 including reference in the claims is to be taken as including reference to the acids when in the form of such derivatives. Equivalence is demonstrated by entry into the biosynthetic pathways of the body as evidenced by effects corresponding to those of the acids themselves or their natural glyceride 65 esters. Thus, indirect identification of useful derivatives is by their having the valuable effect in the body of the fatty acid itself, but conversion, for example, of gamma-linolenic

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acid to dihomo-gamma-llnolenic acid and on to arachidonic the vitamin E is present in a controlled release form in an acid can be shown directly by gas chromatographic analysis amount ranging from about 250 mg to about 400 rag. Most of concentrations in blood, body fat, or other tissue by preferably, the vitamin E is present in an immediate release form in an amount ranging from about 10 mg to about 50 standard techniques, well known to persons of ordinary skill in the art to which the present inventive subject matter 5 rag. pertains. Vitamin B6 may also be present in the composition of the present inventive subject matter. Vitamin B6 is preferably Derivatives of linoleic acid, as used in the present invenpresent in an amount ranging from about 10 mg to about 200 tive subject matter, include, without limitation, salts of linoleic acid, alkaline salts of linoleic acid, esters of linoleic mg. More preferably, vitamin B6 is present in an amount acid, and combinations thereof. Derivatives of linolenic lo ranging from about 20 mg to about 125 rag. Even more preferably, vitamin B6 is present in an immediate release acid, as used in the present inventive subject matter, include, form in an amount ranging from 20 mg to about 50 mg. Most without limitation, salts of linolenic acid, alkaline salts of linolenic acid, esters of linoleic acid, and combinations preferably, vitamin B~ is present in a controlled release form in an amount ranging from 50 mg to about 125 mg. thereof. The salts and alkaline salts herein refer to those regularly used organic or inorganic salts which are accept-15 Folic acid may also be incorporated into the composition able for pharmaceutical use. Non-limiting exemplary lino- of the present inventive subject matter. When folic acid is lenic acids include gamma-linoleic acid and dihomo- present in the composition, it is preferably present in an gamma-linolenic acid. amount ranging from about 0.1 mg to about 3 mg. More preferably, folic acid is present in an immediate release form The fatty acids of the present inventive subject matter 20 in an amount ranging from about 0.1 mg to about 2 mg. Even may be from any source, including, without limitation, more preferably, folio acid is present in a controlled release natural or synthetic oils, fats, waxes or combinations form in an amount ranging from about 1.5 mg to about 3 mg. thereof. Moreover, the fatty acids herein may be derived, Calcium is preferably present in the composition of the without limitation, from non-hydrogenated oils, partially hydrogenated oils, fully hydrogenated oils or combinations present inventive subject matter in an amount ranging from thereof. Non-limiting exemplary sources of fatty acids 25 about 100 mg to about 2,500 rag. More preferably, calcium include seed oil, fish or marine oil, canola oil, vegetable oil, is present in an amount ranging from about 100 mg to about 1,000 mg. Even more preferably, calcium is present in an safflower oil, sunflower oil, nasturtium seed oil, mustard seed oil, olive oil, sesame oil, soybean oil, corn oil, peanut immediate release form in an amount ranging from about oil, cottonseed oil, rice bran oil, babassu nut oil, palm oil, 100 mg to about 500 rag. Most preferably, calcium is present low emcic rapeseed off, palm kernel oil, lupin oil, coconut 3o in a controlled release form in an amount ranging from about oil, flaxseed oil, evening primrose oil, jojoba, tallow, beef 500 mg to about 2,000 mg. tallow, butter, chicken fat, lard, dairy butterfat, shea butter or Magnesium is preferably present in the composition of the combinations thereof. Specific non-limiting exemplary fish present inventive subject matter in an amount ranging from or marine oil sources include shellfish oil, tuna oil, mackerel about 25 mg to about 400 rag. More preferably, magnesium oil, salmon oil, menhaden, anchovy, herring, trout, sardines 35 is present in the composition of the present inventive subject or combinations thereof. Preferably, the source of the fatty matter in an immediate release form in an amount ranging acids is fish or marine oil, soybean oil or flaxseed oil. from about 25 mg to about 100 mg. Even more preferably, The present composition may optionally contain addimagnesium is present in the composition of the present tional vitamins and biologically-acceptable minerals. Non-4o inventive subject matter in a controlled release form in an limiting exemplary vitamins and biologically acceptable amount ranging from about 100 mg to about 400 rag. minerals and their derivatives thereof for inclusion in the The composition of the present inventive subject matter present compositions include vitamin A, B vitamins, vitamin may also include one or more biologically active substance. C, vitamin D, vitamin E, vitamin K, folic acid, iron, calcium, The biologically active substances incorporated into the magnesium, potassium, copper, chromium, zinc, 45 present inventive subject matter are nonteratogenic to promolybdenum, iodine, boron, selenium, manganese, deriva- tect the unborn fetus. For example, without limitation, the tives thereof or combinations thereof. These vitamins and biologically active substance may be a lactogen compound, minerals may be from any source or combination of sources, a derivative of a lactogen compound or combinations without limitation. Non-limiting exemplary B vitamins thereof. Derivatives of lactogen compounds include, without include, without limitation, thiamine, niacinamide, 50 limitation, salts of lactogen compounds, alkaline salts of pyridoxine, riboflavin, cyanocobalamin, biotin, pantothenic lactogen compounds, esters of lactogen compounds and acid or combinations thereof. combinations thereof. When vitamin C is present in the composition of the Various additives may be incorporated into the present present inventive subject matter, it is preferably present in an composition. Optional additives of the present composition amount ranging from about 10 mg to about 500 mg. More 55 include, without limitation, starches, sugars, fats, preferably, the vitamin C is present in an amount ranging antioxidants, amino acids, proteins, derivatives thereof or from about 25 mg to about 400 rag. Even more preferably, combinations thereof. the vitamin C is present an immediate release form in an It is also possible in the nutritional composition of the amount ranging from about 25 mg to about 50 mg. Most present inventive subject matter for the dosage form to preferably, the vitamin C is present in a controlled release 60 combine various forms of release, which include, without form in an amount ranging from about 250 mg to about 500 limitation, immediate release, extended release, pulse mg. release, variable release, controlled release, timed release; sustained release, delayed release, long acting, and combiWhen vitamin E is present in the composition of the nations thereon. The ability to obtain immediate release, present inventive subject matter, it is preferably present in an amount ranging from about 5 mg to about 500 mg. More 65 emended release, pulse release, variable release, controlled release, timed release, sustained release, delayed release, preferably, the vitamin E is present in an amount ranging long acting characteristics and combinations thereof is perfrom about 10 mg to about 400 rag. Even more preferably,

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compression, can be utihzed. Those individuals involved in formed using well known procedures and techniques availpharmaceutical solid dosage form production are well able to the ordinary artisan. Each of these specific techniques versed in the processes and the machinery used as the or procedures for obtaining the release characteristics does chewable dosage form is a very common dosage form in the not constitute an inventive aspect of this inventive subject matter all of which procedures are well known to those of 5 pharmaceutical industry. ordinary skill in the art. As used herein, a "controlled release Fiim coated tablets, for example, without limitation, may form" means any form having at least one component be prepared by coating tablets using techniques such as formulated for controlled release. As used herein, "imme- rotating pan coating methods or air suspension methods to diate reiease form" means any form having all its compodeposit a contiguous film layer on a tablet. This procedure is ~0 often done to improve the aesthetic appearance of tablets, nents formulated for immediate release. Any biologically-acceptable dosage form, and combina- but may also be done to improve the swallowing of tablets, tions thereof, are contemplated by the inventive subject or to mask an obnoxious odor or taste, or to improve to usual matter. Examples of such dosage forms include, without properties of an unsightly uncoated tablet. [imitation, chewable tablets, quick dissolve tablets, effervesCompressed tablets, for example, without limitation, may cent tablets, reconstitutable powders, elixirs, liquids, a5 be prepared by mixing the formulation with excipients solutions, suspensions, emulsions, tablets, multi-layer intended to add binding qualities to disintegration qualifies. tablets, bi-layer tablets, capsules, soft gelatin capsules, hard The mixture is either directly compressed or granulated then gelatin capsules, caplets, lozenges, chewable lozenges, compressed using methods and machinery quite well known beads, powders, granules, particles, microparticles, dispersto those in the industry. The resultant compressed tablet ible granules, cachets, douches, suppositories, creams, 20 dosage units are then packaged according to market need, topicals, inhalants, aerosol inhalants, patches, particle i.e., unit dose, rolls, bulk bottles, blister packs, etc. inhalants, implants, depot implants, ingestibles, injectables, The present inventive subject matter contemplates nutriinfusions, health bars, confections, animal feeds, cereals, tional compositions formulated for administration by any cereal coatings, foods, nutritive foods, functional foods and route, including without limitation, oral, buccal, sublmgual, combinations thereof. The preparation of the above dosage 25 rectal, parenteral, topical, inhalational, injectable and transforms are well known to pemons of ordinary skill in the art. dermal. The physicochemical properties of nutritional The following procedures represent, without limitation, of compositions, their formulations, and the routes of adminacceptable methods of preparing formulations falling within istration are important in absorption. Absorption refers to the the scope of the inventive subject matter. For example, 3o process of nutritional composition movement from the site of administration toward the systemic circulation. Most animal feed may be by methods well known to persons of ordinary skill in the art. Animal feeds may be prepared by orally administered nutritional compositions are in the form mixing the formulation with binding ingredients to form a of tablets or capsules primarily for convenience, economy, plastic mass. The mass is then extruded under high pressure stability, and patient acceptance. They must disintegrate and to form tubular (or "spaghetti-like") structures that are cut to 35 dissolve before absorption can occur. Using the present pellet size and dried. inventive subject matter with any of the above routes of Quick dissolve tablets may be prepared, for example, administration or dosage forms is performed using well without limitation, by mixing the formulation with agents known procedures and techniques available to the ordinary such as sugars and cellulose derivatives, which promote skilled artisan. dissolution or disintegration of the resultant tablet after oral 4o The present inventive subject matter contemplates the use administration, usually within 30 seconds. of biologically-acceptable carriers which may be prepared from a wide range of materials. Without being limited Cereal coatings may be prepared, for example, without limitation, by passing the cereal formulation, after it has thereto, such materials include diluents, binders and been formed into pellets, flakes, or other geometric shapes, adhesives, lubricants, plasticizers, disintegrants, colorants, under a precision spray coating device to deposit a film of 45 bulking substances, flavorings, sweeteners and miscellaactive ingredients, plus excipients onto the surface of the neous materials such as buffers and adsorbents in order to formed elements. The units thus treated are then dried to prepare a particular medicated composition. form a cereal coating. Binders may be selected from a wide range of materials For example, health bars may be prepared, without such as hydroxypropylmethylcellulose, ethylcellulose, or limitation, by mixing the formulation plus excipients (e.g., 50 other suitable cellulose derivatives, povidone, acrylic and binders, fillers, flavors, colors, etc.) to a plastic mass conmethacrylic acid co-polymers, pharmaceutical glaze, gums, milk derivatives, such as whey, starches, and derivatives, as sistency. The mass is then either extended or molded to form "candy bar" shapes that are then dried or allowed to solidify well as other conventional binders well known to persons skilled in the art. Exemplary non-limiting solvents are water, to form the final product. Soft gel or soft gelatin capsules may be prepared, for 55 ethanol, isopropyl alcohol, methylene chloride or mixtures and combinations thereof. Exemplary non-limiting bulking example, without limitation, by dispersing the formulation substances include sugar, lactose, gelatin, starch, and silicon in an appropriate vehicle (vegetable oils are commonly dioxide. used) to form a high viscosity mixture. This mixture is then encapsulated with a gelatin based film using technology and The plasticizers used in the dissolution modifying system machinery known to those in the soft gel industry. The 60 are preferably previously dissolved in an organic solvent and added in solution form. Preferred plasticizers may be industrial units so formed are then dried to constant weight. selected from the group consisting of diethyl phthalate, Chewable tablets, for example, without limitation, may be diethyl sebacate, triethyl citrate, cronotic acid, propylene prepared by mixing the formulations with excipients glycol, butyl phthalate, dibutyl sebacate, caster oil and designed to form a relatively soft, flavored, tablet dosage form that is intended to be chewed rather than swallowed. 65 mixtures thereof, without limitation. As is evident, the plasticizers may be hydrophobic as well as hydrophilic in Conventional tablet machinery and procedures, that is both direct compression and granulation, i.e., or slugging, before nature. Water-insoluble hydrophobic substances, such as

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diethyl phthalate, diethyl sebacate and caster oil are used to delay the release of water-soluble vitamins, such as vitamin B6 and vitamin C. In contrast, hydrophilic plasticizers are used when water-insoluble vitamins are employed which aid in dissolving the encapsulated film, making channels in the surface, which aid in nutritional composition release. The composition of the present inventive subject matter may be administered in a partial, i.e., fractional dose, one or more times during a 24 hour period, a single dose during a 24 hour period of time, a double dose during a 24 hour period of time, or more than a double dose during a 24 hour period of time. Fractional, double or other multiple doses may be taken simultaneously or at different times during the 24 hour period. The compositions of the present invention are intended for use by humans and other mammals. The dosages are adjusted according to body weight and thus may be set forth herein on a per body weight basis. For example, if the formula specifies a range of about 10-1000 mg for a 55 kg individual, that range would be adjusted for a 35 kg individual to about 6.3-63 mg (e.g., the lower range limit=(35 kg/55 kg) "10 mg=6.3 mg). Decimal amounts may be rounded to the nearest whole number. In the above manner the present compositions may thus be adapted to be suitable for any individual, including any mammal, regardless of its size. The present composition is adapted to meet the specific physiological needs of a breast-feeding mother. For example, the formulations may focus on special nutritional needs of the mother that are not generally addressed in prenatal supplements, such as essential fatty acids, iron and calcium, without limitation. The iron and calcium, when ¯ present, are provided in amounts to optimize nutritional benefit to the mother, while minimizing unpleasant side effects which may accompany overly large doses. The formulation can be further tailored based upon the specific needs, genetic predispositions or identified deficiencies of women. Moreover, the present composition can be used as one component of a prescribed therapy. Biologically-acceptable calcium compounds include, but are not limited to, any of the well known calcium supplements, such as calcium carbonate, calcium sulfate, calcium oxide, calcium hydroxide, calcium apatite, calcium citrate-malate, bone meal, oyster shell, calcium gluconate, calcium lactate, calcium phosphate, calcium levulinate, and the like. Biologically-acceptable magnesium compounds which may be incorporated into the present inventive subject matter include, but are not limited to, magnesium stearate, magnesium carbonate, magnesium oxide, magnesium hydroxide and magnesium sulfate. The compositions of the inventive subject matter may be provided in a blister pack or other such pharmaceutical package, without limitation. Further, the compositions of the present inventive subject matter may further include or be accompanied by indicia allowing women to identify the compositions as products for persons planning to or currently breast-feeding their infants. The indicia may further additionally include an indication of the above specified time periods for using said compositions. The composition of the present inventive subject matter is preferably administered during a period commencing no later than at least the tenth week of pregnancy. More preferably, the composition is administered during a period of time commencing on about the tenth week of pregnancy and continuing through to completion of breast-feeding or continuing on as a nutritional supplement tbr the mother.

16
The present inventive subject matter includes a method for enriching the breast milk of women to optimize neurological development of infant's breast-fed by said women. The methods include administration of the present compo5 sition to women during a critical period. The critical period of administration is the period commencing at least at about the tenth week of pregnancy and terminating at the conclusion of breast-feeding or continuing on as a nutritional supplement for the mother. ao The present composition and method may increase lactogenesis or the quantity of breast milk produced during lactation. Further, the compositions and methods may prevent or at least minimize fatty acid deficiency in lactating women. The quality of breast milk may also be improved by ~5 the compositions and methods. Moreover, the duratinn of the period of lactation may be extended by the present compositions and methods. Thus, women who would have digculty breast-feeding for more than four weeks after pregnancy when not taking the present composition, could 20 breast-feed for more than four weeks after pregnancy when taking the present composition. The foregoing is considered as illustrative only of the principles of the inventive subject matter. Purther, since numerous modifications and changes will readily occur to 25 those skilled in the art, it is not desired to limit the inventive subject matter to the exact construction and operation shown and described, and accordingly all suitable modifications and equivalents may be resorted to, falling within the scope of the inventive subject matter. 3o The following examples are illustrative of preferred embodiments of the inventive subject matter and are not to be construed as limiting the inventive subject matter thereto. All percentages are based on the percent by weight of the final delivery system or formulation prepared unless other35 wise indicated and all totals equal 100% by weight. EXAMPLES Example 1 40 The following formulations are used to prepare compositions for administration to women prior to and during lactation:

45

Component (in mg unless otherwise indicated) Linoleic Acid Linolenic Acid Omega-3 Fatty Acid Omega-2 Fatty Acid Vitamin C Vitamin E (I.U.) Vitamin A (I.U.) Vitamin Da (LU.) Vitamin B6 Iron Calcium Mierocrystalline Cellulose Starch Silicon Dioxide Magnesium Stearate

Formula I 10 10 10 -25 10 2700 400 20 90 2500 200 200 3 10

Formula II 100 100 10 -400 400 2700 400 125 90 400 200 200 5 12

Formula II[ 20 20 50 50 700 200 2700 400 20 90 1000 200 200 5 15

50

55

60

Example 2 65 The following compositions are used to prepare controlled release products for administration to women prior to and during lactation:

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iron, magnesium, and calcium are then added and blended together to form a uniform biologically active mixture. The mixture is then cooled to 30 degrees Celsius to form a Component Controlled Controlled viscous biologically active core composition, after which Release (in mg unless Realease 5 time the composition is ready for encapsulation in a soft otherwise indicated) Formula A Formula B gelatin shell. Linoleic Acid 20 20 A soft gelatin shell is prepared by heating purified water Linolenic Acid 20 20 in a suitable vessel and then adding gelatin. This water Omega-3 Fatty Acid 50 50 Omega-2 Fatty Acid 50 50 gelatin mixture is mixed until the gelatin is fully dissolved, Vitamin C 250 400 10 and then glycerin, preservative, one or more flavors, and one Vitamin B (I.U.) 200 400 or more colorants are added. This gelatin mixture is blended 2700 -Vitamin A (I.U,) well and cooled. The shells are then filled with the core Vitamin Ds (I.U.) 400 -125" 125" composition and formed in accordance with soft gelatin Vitamin Be Iron 90* -techniques commonly used and well known to persons of Calcium 500 100 15 skill in the art. Microcrystalline 200 200 Cellulose The inventive subject matter being thus described, it will Starch 200 200 be apparent that the same may be varied in many ways. Such Silicon Dioxide 5 1 variations are not to be regarded as a departure from the Magnesium Steamte 15 15 spirit and scope of the inventive subject matter, and all such Ethylcellulose 60 60 20 modifications are intended to be within the scope of the Folio Acid -Magnesium -25 appended claims. We claim: *formulated for controlled release 1. A composition for administration to a woman for enriching the breast milk of said woman to optimize neu25 rological development of an infant breast-fed by the woman, Example 3 which comprises: The follo~ving compositions are used to prepare products a) about 10 mg to 100 mg of a first fatty acid compound for administration to women prior to and during lactation: for each compound selected from the group consisting of a linoleic acid compound, a linolenic acid 3o compound, a derivative thereof and a combination thereof; VIII IX Component IV V VI VII b) about 10 mg to 1000 mg of a second fatty acid Linolelc Acid 10 100 20 10 100 20 compound selected from the group consisting of a Linolenic Acid 10 100 20 10 100 20 docosahexaenoic acid compound, an omega-3 fatty Omega-3 Fatty 10 10 50 10 10 50 35 acid, an omega-2 fatty acid, a derivative thereof and a Acid Omega-2 Fatty --50 --50 combination thereof; Acid c) about 10 mg to 125 mg of a vitamin B6 compound or 125 Vitamin B6 20 125 20 20 20 derivative thereof; Folic Acid 0.1 3 1 0.1 3 Calcium 100 400 1000 100 1000 1000 40 d) about 0.1 mg to 3 mg of a folic acid compound or ---25 400 25 Magnesium derivative thereof; 400 Vitamin C ---25 400 e) about 100 mg to 2,000 mg of a calcium compound or ---10 400 400 Vitamin E (I.U.) derivative thereof; Microcrystalline 100 100 200 100 100 100 Cellulose f) about 25 mg to 500 mg of a vitamin C compound or Starch 100 100 200 100 100 100 derivative thereof; 1 45 Silicon Dioxide 0.3 0.7 1 0.3 1 g) about 10 mg to 400 mg of a vitamin E compound or Magnesium 3 7 15 3 15 15 Stearate derivative thereof; and Lactose 100 --100 --wherein the weight ratio of said first fatty acid comEthylcellulose pound to said second fatty acid compound is about 1:0.1 to 10, said weight ratio specifically formulated 50 to enrich the breast milk of the woman to optimize The above components are in mg unless otherwise indineurological development of an infant breast-fed by cated. Tablets incorporating the above formulations are the woman. prepared using conventional methods and materials known 2. The composition of claim 1, wherein said composition in the pharmaceutical art. The resulting nutritional compo55 additionally contains a biologically active substance. sitions were recovered and stored for future use. 3. The composition of claim 2, wherein the biologically active substance is a lactogen compound or derivative Example 4 thereof. A soft gelatin supplement may be prepared, by first 4. The composition of claim 1, wherein said composition combining mineral oil and soybean oil in a first vessel and 60 is administered during a period commencing no later than blending it to form a uniform oil mixture, heating the oil the tenth week of pregnancy. 5. The composition of claim 1, wherein said composition mixture to 45 degrees Celsius, and then adding propylene is administered during a period of time commencing at least glycol. In a second vessel preheated to 70 degrees Celsiu