Free Joint Claim Construction Worksheet - District Court of California - California

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AntiCancer, Inc. v. Teco Diagnostics, et al. U.S. District Court Case No. 07-CV-2294-L (BLM) July 11, 2008 Joint Claim Construction Worksheet
U.S. Patent No. 5,998,191 Claim Language `191 Patent 1. A diagnostic kit for use in a single enzyme assay of the homocysteine concentration in a biological fluid of a subject, said kit comprising: Agreed Proposed Claim Construction Enzyme: A protein that acts as a catalyst to induce chemical changes in other substances, itself remaining apparently unchanged by the process. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "enzyme". Homocysteine: A compound found in biological fluids such as urine, whole blood, and blood plasma. Support in Specification: `191, Col. 1, 16-18 AntiCancer's Proposed Construction Defendant's Proposed Construction Court's Construction

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Claim Language `191 Patent (a) a homocysteinase enzyme; and

Agreed Proposed Claim Construction Homocysteinase enzyme: Enzymes capable of catalyzing reactions whereby hydrogen sulfide is produced from homocysteine. Support in Specification: `191, Col. 8, 52-54

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(b) at least one reagent capable of being used to determine the amount of product hydrogen sulfide formed by reaction of homocysteinase on homocysteine;

Reagent: Any substance added to a solution of another substance to participate in a chemical reaction. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "reagent".

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Claim Language `191 Patent wherein said homocysteinase has the property that at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting a biological fluid in an assay for homocysteine is contributed by said homocysteine, when the concentrations of homocysteine and cysteine in said fluid are, respectively, :molar and about 300 :molar respectively, and

Agreed Proposed Claim Construction Cysteine: A compound found in biological fluids. Support in Specification: In the Abstract Assay: 1. The quantitative or qualitative evaluation of a substance for impurities, toxicity, etc; the results of such an evaluation; 2. To examine; to subject to analysis; 3. Test of purity; trial. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "assay".

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wherein said homocysteinase is that of Pseudomonas, Clostridium, Aeromonas or Trichomonas wherein one or more peptide sequences of such enzyme are correspondingly replaced by a sequence selected from the group consisting of residues 43-51,

Pseudomonas, Clostridium, Aeromonas or Trichomonas: Bacterial species._ Peptide: A compound of two or more amino acids.

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Claim Language `191 Patent residues 168-176 and residues 304- 312 of SEQ ID NO:10.

Agreed Proposed Claim Construction Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "peptide". Residues: A portion of a larger molecule, in this case residues are amino acids.

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2. The diagnostic kit of claim 1 further comprising one or more reagents selected from the group consisting of: (a) an agent capable of reducing disulfide bonds;

See above

Reducing: In chemistry, a reaction involving a gain of one or more electrons by a substance, such as when iron passes from, or when hydrogen is added to the double bond of an organic compound. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "reduction". Disulfide bonds: Two sulfur atoms connected by a double bond.

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Claim Language `191 Patent (b) a source of ferric iron;

Agreed Proposed Claim Construction Ferric: Relating to iron, especially denoting a salt containing iron in its higher (triad) valence, Fe3+. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "ferric".

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(c) an N,N-dialkyl-pphenylenediamine; and

N,N-dialkyl-pphenylenediamine: An organic compound that can be oxidized to form a colored dye. Support in Specification: `191, Col. 28, 35-44

(d) homocysteine as a calibration standard.

Calibration: The act of standardizing or calibrating an instrument or laboratory procedure. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "calibration".

3. The diagnostic kit of claim 1 comprising:

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Claim Language `191 Patent (a) SEQ ID NO: 10, or residues Met1 through Leu396 thereof, as homocysteinase; (b) the reagents 50 mM borate buffer, pH 7.5; 100 mM DL-dithiothreitol; 10 mM potassium ferricyanate, 1% w/v Triton® X-100; a 100 mM solution of N,Ndialkyl-phenylene diamine selected from the group consisting of dimethyl, diethyl, dipropyl or dibutyl; and (c) homocysteine or homocystine as a calibration standard.

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Homocystine: The disulfide bonded dimmer of homocysteine. Support in Specification: `191, Col. 32, 5-10

6. The diagnostic kit of claim 1 wherein said homocysteinase comprises the amino acid sequence set forth as positions 1-396 of SEQ ID NO: 10.

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Claim Language `191 Patent 7. A diagnostic kit for use in a single enzyme assay of the homocysteine concentration in a biological fluid of a subject, said kit comprising: (a) a homocysteinase enzyme having the amino acid sequence of positions 1396 of SEQ ID NO: 10; and (b) at least one reagent capable of being used to determine the amount of product hydrogen sulfide formed by reaction of said homocysteinase on homocysteine.

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U.S. Patent No. 6,066,467 Claim Language `467 Patent 1. A diagnostic kit for use in a single enzyme assay of the homocysteine concentration in a biological fluid of a subject, said kit comprising: Agreed Proposed Claim Construction Enzyme: A protein that acts as a catalyst to induce chemical changes in other substances, itself remaining apparently unchanged by the process. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "enzyme". Homocysteine: A compound found in biological fluids such as urine, whole blood, and blood plasma. Support in Specification: `467, Col. 1, 18-20 (a) a homocysteinase enzyme; and Homocysteinase enzyme: Enzymes capable of catalyzing reactions whereby hydrogen sulfide is produced from homocysteine. Support in Specification: `467, Col. 9, 32-34 AntiCancer's Proposed Construction Defendant's Proposed Construction Court's Construction

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Claim Language `467 Patent (b) at least one reagent capable of being used to determine by fluorescence the amount of product hydrogen sulfide formed by reaction of homocysteinase on homocysteine;

Agreed Proposed Claim Construction Steadman's Online Medical Dictionary; www.steadmans.com, definition for "reagent". Fluorescence: Emission of a longer wavelength radiation by a substance as a consequence of absorption of energy from a shorter wavelength radiation, continuing only as long as the stimulus is present; distinguished from phosphorescence, which emission persists for a perceptible period of time after the stimulus has been removed. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "fluorescence".

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Claim Language `467 Patent said homocysteinase is sufficiently non-reactive toward cysteine that any hydrogen sulfide produced by reaction of said homocysteinase on cysteine does not substantially interfere with the use of said kit to assess risk for cardiovascular disease. 2. The diagnostic kit of claim 1 wherein the homocysteinase included therein has the property that at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting a biological fluid in an assay for homocysteine is contributed by said homocysteine, when the concentrations of homocysteine and cysteine in said fluid are, respectively, about 5-15 :molar and about 100-300 :molar respectively.

Agreed Proposed Claim Construction Cysteine: A compound found in biological fluids. Support in Specification: In the Abstract

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Assay: 1. The quantitative or qualitative evaluation of a substance for impurities, toxicity, etc; the results of such an evaluation; 2. To examine; to subject to analysis; 3. Test of purity; trial. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "assay".

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Claim Language `467 Patent 3. The diagnostic kit of claim 1 wherein said homocysteinase included therein has the property that at least about 99% of the hydrogen sulfide produced by action of said homocysteinase upon contacting said biological fluid in an assay for homocysteine is contributed by said homocysteine. 4. The diagnostic kit of claim 1 capable of being used to determine a homocysteine concentration in said biological fluid in the range of 1-500 :molar, wherein said fluid also contains about 10 to about 1000 :molar of cysteine. 5. The diagnostic kit of claim 1 capable of being used to determine the homocysteine concentration in tissue fluid, blood, blood plasma, blood serum or urine.

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Claim Language `467 Patent 6. The diagnostic kit of claim 1 further comprising one or more reagents selected from the group consisting of: (a) an agent capable of reducing disulfide bonds;

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Reducing: In chemistry, a reaction involving a gain of one or more electrons by a substance, such as when iron passes from, or when hydrogen is added to the double bond of an organic compound. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "reduction". Disulfide bonds: Two sulfur atoms connected by a double bond.

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Claim Language `467 Patent (b) a source of ferric iron;

Agreed Proposed Claim Construction Ferric: Relating to iron, especially denoting a salt containing iron in its higher (triad) valence, Fe3+. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "ferric".

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(c) an N,N-dialkyl-pphenylene diamine; and

N,N-dialkyl-pphenylenediamine: An organic compound that can be oxidized to form a colored dye. Support in Specification: '467, Col. 29, 36-55

(d) homocysteine as a calibration standard.

Calibration: The act of standardizing or calibrating an instrument or laboratory procedure. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "calibration".

7. The diagnostic kit of claim 1 comprising:

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Claim Language `467 Patent (a) SEQ ID NO: 10, or residues Met1 through Leu396 thereof, as homocysteinase in a concentration of 0.011000 :M/ml; (b) at least one buffer having a concentration of 10 mM-1 M and a pH of 7-9.5 selected from the group consisting of sodium phosphate buffer, tris buffer and borate buffer; and at least one reducing agent having a concentration of 0.1 mM-1 M selected from the group consisting of DLdithiothreitol, TCEP, and $mercaptoethanol; 0.01-100 mM potassium ferricyanate, 0.1-10% w/v surfactant (detergent); a 0.01-100 mM solution of N,N-dialkylphenylene diamine having a dialkyl group selected from the group consisting of dimethyl, diethyl, dipropyl and dibutyl; and

Agreed Proposed Claim Construction Residues: A portion of a larger molecule.

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Buffer: A mixture of an acid and its conjugate base (salt) when present in a solution, reduces any changes in pH that would otherwise occur. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "buffer".

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Claim Language `467 Patent (c) homocysteine and/or homocystine as a calibration standard.

Agreed Proposed Claim Construction Homocystine: The disulfide bonded dimmer of homocysteine. Support in Specification: '467, Col. 33, 29-33

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8. In a method for determining the amount of homocysteine present in a biological fluid of a subject wherein said method comprises the step of contacting said sample with an enzyme capable of catalyzing production from homocysteine of a detectable quantity of hydrogen sulfide, and wherein said sample further comprises an amount of cysteine from which a detectable quantity of hydrogen sulfide can be produced that interferes with said determination, the improvement comprising

Catalyzing: A catalysts is a substance that accelerates a chemical reaction but is not consumed or changed permanently thereby. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "catalyst".

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Claim Language `467 Patent selecting, for use therein, a homocysteinase having the property that at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting said biological fluid therewith, in an assay for homocysteine, is contributed by said homocysteine, when the concentrations of homocysteine and cysteine in said fluid are, respectively, about 1-500 :molar and about 10-1000 :molar respectively, and measuring by fluorescence the amount of product hydrogen sulfide formed. 9. A single enzyme method for determining the concentration of homocysteine in a biological fluid of a subject that comprises use of a diagnostic kit according to claim 1.

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Claim Language `467 Patent 10. A diagnostic method to assess risk for cardiovascular disease in a subject, wherein the concentration of homocysteine in a biological fluid of said subject is determined, absent interference from concentrations of cysteine and methionine in said fluid, said method comprising the steps of: (a) contacting the biological fluid sample with an agent capable of reducing disulfide bonds in order to liberate as free homocysteine that fraction of total homocysteine present therein in disulfide-bonded form;

Agreed Proposed Claim Construction Methionine: A compound found in biological fluids. Support in Specification: In the Abstract

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Claim Language `467 Patent (b) contacting said sample with a homocysteinase that is substantially non-reactive to cysteine compared to homocysteine, such that at least about 90% of the hydrogen sulfide produced by said contacting is produced from homocysteine, under conditions where said hydrogen sulfide does not escape; (c) adding ferric iron and an N,N-dialkyl-phenylene diamine to said hydrogen sulfide-containing sample in order to produce, in situ, a methylene blue-type chromophore; (d) determining by fluorescence the concentration of homocysteine that was present in said sample based on the concentration of chromophore produced; and

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Chromophore: A colored compound that can be detected by a Spectrophotometer. Support in Specification: '467, Col. 33, 27-29 See above

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Claim Language `467 Patent (e) comparing said result to levels of homocysteine in biological fluids of subjects that are known to correlate with increased risk for cardiovascular disease. 11. The method of claim 10 wherein said homocysteinase is SEQ ID NO: 10, or residues Met1 through Leu396 thereof. 12. The method of claim 10 wherein said biological fluid sample is selected from the group consisting of tissue fluid, urine, blood, blood serum, and blood plasma. 13. The diagnostic kit of claim 1 comprising: (a) a homocysteinase that is substantially non-reactive to cysteine compared to homocysteine; (b) a buffer, a reducing agent, an agent useful to detect hydrogen sulfide by fluorescence; and optionally,

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Claim Language `467 Patent (c) homocysteine and/or homocystine as a calibration standard. 14. The diagnostic kit defined in claim 7 wherein the buffer is sodium phosphate having a pH of about 8.3, the reducing agent is DL-dithiothreitol, and the N,N-dialkyl-phenylene diamine is N,N-dibutylphenylene diamine. 15. In a method for determining the amount of homocysteine present in a sample of biological fluid of a subject containing 1-1000 :M homocysteine using the diagnostic kit of claim 7,

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Claim Language `467 Patent wherein said method comprises the step of contacting said sample with an enzyme capable of catalyzing production from homocysteine of a detectable quantity of hydrogen sulfide, and wherein said sample further comprises an amount of cysteine from which a detectable quantity of hydrogen sulfide can be produced that interferes with said determination, the improvement comprising selecting, for use therein, a homocysteinase having the property that at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting said biological fluid therewith, in an assay for homocysteine, is contributed by said homocysteine, when the concentrations of homocysteine and cysteine in said fluid are, respectively, about 1 to about 500 :molar and about 10 to about 1000 :molar respectively, and

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Claim Language `467 Patent measuring by fluorescence the amount of product hydrogen sulfide formed; wherein homocysteinase is added to said sample in an amount needed to achieve a final concentration of 0.011000 :g/ml; and wherein reagents are added in amounts needed to achieve final concentrations of 1-100 mM of buffer; 0.01100 mM reducing agent; 0.01-10 mM potassium ferricyanate, 0.01-1.0% w/v surfactant; and about 0.01-10 mM solution of N,N-dialkylphenylene diamine. 16. The method defined in claim 15 wherein homocysteinase is added in an amount needed to achieve a final concentration of about 1 :g/ml; and

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Claim Language `467 Patent wherein the buffer is sodium phosphate added in an amount needed to achieve a final concentration of about 10 mM, the reducing agent is DL-dithiothreitol added in an amount needed to achieve a final concentration of about 0.5 mM, and the N,Ndialkyl-phenylene diamine is N,N-dibutyl-phenylene diamine added in an amount needed to achieve a final concentration of about 0.5 mM, and wherein potassium ferricyanate and the surfactant are added in amounts needed to achieve final concentrations of about 0.25 mM and 0.1% w/v, respectively.

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Claim Language `467 Patent 17. A method of using the diagnostic kit defined in claim 7 to assess risk for cardiovascular disease in a subject, wherein a concentration of a subject's biological fluid sample containing 1-1000 :M homocysteine is determined, absent interference from concentrations of cysteine and methionine in said fluid, said method comprising the steps of: (a) adding to said sample said buffer in an amount needed to achieve a final concentration of 1-100 Mm; (b) contacting the buffered sample with reducing agent in an amount needed to achieve a final concentration of 0.01-100 mM reducing agent, wherein said reducing agent is capable of reducing disulfide bonds in order to liberate as free homocysteine that fraction of total homocysteine present therein in disulfide-bonded form;

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Claim Language `467 Patent (c) contacting said sample containing the reducing agent with homocysteinase, in an amount needed to achieve a final concentration of 0.01-1000 :g/ml homocysteinase, wherein said homocysteinase is substantially non-reactive to cysteine compared to homocysteine, such that at least about 90% of the hydrogen sulfide produced by said contacting is produced from homocysteine, under conditions where said hydrogen sulfide does not escape;

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Claim Language `467 Patent (d) adding potassium ferricyanate and surfactant, in an amount needed to achieve a final concentration of 0.01-10 mM of potassium ferricyanate, 0.01-1% (w/v) of surfactant, and N,Ndialkyl-phenylene diamine in an amount needed to achieve a final concentration of 0.0110 mM, to said hydrogen sulfide-containing sample in order to produce, in situ, a methylene blue-type chromophore; (e) determining by fluorescence the concentration of homocysteine that was present in said sample based on the concentration of chromophore produced; and (f) comparing said result to levels of homocysteine in biological fluids of subjects that are known to correlate with increased risk for cardiovascular disease.

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Claim Language `467 Patent 18. The method defined in claim 17 wherein homocysteinase is added in an amount needed to achieve a final concentration of about 1 :g/ml; and wherein the buffer is sodium phosphate added in an amount needed to achieve a final concentration of about 10 mM, the reducing agent is DL-dithiothreitol added in an amount needed to achieve a final concentration of about 0.5 mM, and the N,Ndialkyl-phenylene diamine is N,N-dibutyl-phenylene diamine added in an amount needed to achieve a final concentration of about 0.5 mM, and wherein reagents are added in amounts needed to achieve final concentrations of about 0.25 mM potassium ferricyanate and about 0.1% (w/v) surfactant.

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U.S. Patent No. 6,140,102

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Claim Language `102 Patent 1. A diagnostic kit for use in a single enzyme assay of the homocysteine concentration in a biological fluid of a subject, said kit comprising:

Agreed Proposed Claim Construction Enzyme: A protein that acts as a catalyst to induce chemical changes in other substances, itself remaining apparently unchanged by the process. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "enzyme". Desulfurase: An enzyme that catalyzes the removal of sulfur, usually as hydrogen sulfide, from organic compounds. Homocysteine: A compound found in biological fluids such as urine, whole blood, and blood plasma. Support in Specification: '102, Col. 1, 17-19 Substrate: Cysteine: A compound found in biological fluids.

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Claim Language `102 Patent wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas wherein any of the following amino acid replacements modify said desulfurase: (a) the amino acid corresponding to Phe47 of mgl-1 (SEQ ID NO:12) is replaced by Leu, Ile, Val, Ala, Gly, Met or Trp; (b) the amino acid corresponding to Asp172 of mgl-1 (SEQ ID NO:12) is replaced by Glu, Gln or Asn; (c) the amino acid corresponding to Ser308 of mgl-1 (SEQ ID NO:12) is replaced by Tyr, Phe, Met, Trp, Gln, Thr or Asn.

Agreed Proposed Claim Construction Amino Acid: An organic acid in which one of the hydrogen atoms on a carbon atom has been replaced by NH2.

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Claim Language `102 Patent 2. The enzyme of claim 1 wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 3. The enzyme of claim 1 which further comprises at least one histidine residue at the N-terminus.

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N-terminus: The -NH2 group or the aminoacyl residue containing it at one end of a peptide or protein. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "aminoterminal".

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Claim Language `102 Patent 4. A purified and isolated enzyme having desulfurase activity with respect to homocysteine as a substrate in preference to cysteine as a substrate such that the amount of hydrogen sulfide liberated from treatment of a sample of blood, urine, tissue fluid, serum, or plasma of a subject with said enzyme is substantially generated from the homocysteine and not from the cysteine in said sample, wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas wherein any of the following amino acid replacements modify said desulfurase: (a) a Leu-containing fragment of Gly-Gly-AsnArg-Leu-Ala-Gly-Gln-Glu (SEQ ID NO:10, residues 43-51); or

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Claim Language `102 Patent (b) a Glu-containing fragment of Arg-Val-CysLys-Glu-Ala-His-Ser-Gln (SEQ ID NO:10, residues 168-176); or (c) a Tyr-containing fragment of Gln-Met-ArgMet-Tyr-Gly-Ser-Met-Ile (SEQ ID NO:10, residues 304-312) replaces the corresponding sequence in said derived desulfurase. 5. The enzyme of claim 4 wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 6. The enzyme of claim 4 which further comprises at least one histidine residue at the N-terminus.

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Claim Language `102 Patent 7. The desulfurase enzyme of claim 2 wherein any of the sequences

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(a) Gly-Gly-Asn-Arg-LeuAla-Gly-Gln-Glu (SEQ ID NO:10, residues 43-51); or (b) Arg-Val-Cys-Lys-GluAla-His-Ser-Gln (SEQ ID NO:10, residues 168-176); or (c) Gln-Met-Arg-Met-TyrGly-Ser-Met-Ile (SEQ ID NO:10, residues 304-312); replaces the corresponding sequence in said derived desulfurase. 8. The enzyme of claim 7 wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 9. The enzyme of claim 7 which further comprises at least one histidine residue at the N-terminus. See above

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Claim Language `102 Patent 10. A purified and isolated enzyme having desulfurase activity with respect to homocysteine as a substrate at least 100 times greater than that with respect to cysteine as a substrate when said substrates are present in a physiological fluid, wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas wherein any of the following amino acid replacements modify said desulfurase: (a) the amino acid corresponding to Phe47 of mgl-1 (SEQ ID NO:12) is replaced by Leu, Ile, Val, Ala, Gly, Met or Trp; (b) the amino acid corresponding to Asp172 of mgl-1 (SEQ ID NO:12) is replaced by Glu, Gln or Asn;

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

See above

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Claim Language `102 Patent (c) the amino acid corresponding to Ser308 of mgl-1 (SEQ ID NO:12) is replaced by Tyr, Phe, Met, Trp, Gln, Thr or Asn. 11. The enzyme of claim 10 wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 12. The enzyme of claim 10 which further comprises at least one histidine residue at the N-terminus. 13. A purified and isolated enzyme having desulfurase activity with respect to homocysteine as a substrate at least 100 times greater than that with respect to cysteine as a substrate when said substrates are present in a physiological fluid,

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

See above

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Claim Language `102 Patent wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas wherein any of the following amino acid replacements modify said desulfurase sequences (a) a Leu-containing fragment of Gly-Gly-AsnArg-Leu-Ala-Gly-Gln-Glu (SEQ ID NO:10, residues 43-51); or (b) a Glu-containing fragment of Arg-Val-CysLys-Glu-Ala-His-Ser-Gln (SEQ ID NO:10, residues 168-176); or (c) a Tyr-containing fragment of Gln-Met-ArgMet-Tyr-Gly-Ser-Met-Ile (SEQ ID NO:10, residues 304-312) replaces the corresponding sequence in said derived desulfurase.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

See above

See above

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Claim Language `102 Patent 14. The enzyme of claim 13 wherein said desufurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 15. The enzyme of claim 13 which further comprises at least one histidine residue at the N-terminus. 16. The desulfurase enzyme of claim 13 wherein any of the sequences (a) Gly-Gly-Asn-Arg-LeuAla-Gly-Gln-Glu (SEQ ID NO:10, residues 43-51); (b) Arg-Val-Cys-Lys-GluAla-His-Ser-Gln (SEQ ID NO:10, residues 168-176); and (c) Gln-Met-Arg-Met-TyrGly-Ser-Met-Ile (SEQ ID NO:10, residues 304-312); replaces the corresponding sequence in said derived desulfurase.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

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Claim Language `102 Patent 17. The enzyme of claim 16 wherein said desulfurase enzyme has the amino acid sequence of a desulfurase derived from Pseudomonas or Trichomonas. 18. The enzyme of claim 16 which further comprises at least one histidine residue at the N-terminus. 19. A purified and isolated desulfurase enzyme which comprises the amino acid sequence set forth as positions 1-396 in SEQ ID NO:10 or a fragment thereof that retains the activity and specificity of said amino acid sequence. 20. The enzyme of claim 19 which further comprises at least one histidine residue at the N-terminus. 21. The enzyme of claim 19 which comprises the amino acid sequence set forth as positions 1-396 in SEQ ID NO:10.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

See above

See above

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Claim Language `102 Patent 22. The enzyme of claim 21 which further comprises at least one histidine residue at the N-terminus.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

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U.S. Patent No. 6,468,762 Claim Language `762 Patent 1. A purified and isolated homocycsteinase which has the amino acid sequence of SEQ. ID No. 10 or variant thereof wherein said homocysteinase has the property that at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting a biological fluid is contributed by homocysteine, when the concentrations of homocysteine and cysteine in said fluid are, respectively, about 5-15: molar and about 100-300: molar respectively. Agreed Proposed Claim Construction Homocysteinase: a desulfurase that decomposes homocysteine to yield hydrogen sulfide, ammonia, and alpha-ketobutyrate. Support in Specification: `762, Col. 1, 48-50 Variant: Variants include a homocysteinase that is a substitution variant, addition variant, deletion variant, or other derivatives. Support in Specification: `762, Col. 9, 1-4 Homocysteine: A compound found in biological fluids. Support in Specification: In the Abstract Cysteine: A compound found in biological fluids. Support in Specification: In the Abstract AntiCancer's Proposed Construction Defendant's Proposed Construction Court's Construction

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Claim Language `762 Patent 2. The homocysteinase of claim 1 wherein at least about 99% of the hydrogen sulfide produced by action of said homocysteinase upon contacting a biological fluid is contributed by homocysteine when the concentrations of homocysteine and cysteine in said fluid are, respectively, about 5-15: molar and about 100-300: molar. 3. The homocysteinase of claim 1 wherein at least about 90% of the hydrogen sulfide produced by action of said homocysteinase upon contacting a biological fluid is contributed by homocysteine when the fluid contains 5: molar homocysteine 1000: molar cysteine.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

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Claim Language `762 Patent 4. The homocysteinase of claim 1 which has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas or a mutated form thereof.

Agreed Proposed Claim Construction Desulfurase: An enzyme that catalyzes the removal of sulfur, usually as hydrogen sulfide, from organic compounds.

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

5. The homocysteinase of claim 1 which further comprises at least one histidine residue at the Nterminus.

N-terminus: The -NH2 group or the aminoacyl residue containing it at one end of a peptide or protein. Other Support: Steadman's Online Medical Dictionary, www.steadmans.com, definition for "aminoterminal".

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Claim Language `762 Patent 6. A purified and isolated homocysteinase which has the amino acid sequence of SEQ. ID No. 10 or variant thereof having desulfurase activity to homocysteine as a substrate compared to cysteine as a substrate such that the amount of hydrogen sulfide liberated from treatment of a sample of blood, urine, tissue fluid, serum, or plasma of a subject with said enzyme is substantially generated from the homocysteine and not from the cysteine in said sample, when the concentration of homocysteine is ten fold less than the concentration of cysteine in said sample. 7. The homocysteinase of claim 6 which has the amino acid sequence of a desulfurase derived from Pseudomonas Clostridium, Aeromonas or Trichomonas or a mutated form thereof.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

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Claim Language `762 Patent 8. The homocysteinase of claim 6 which further comprises at least one histidine residue at the Nterminus. 9. A purified and isolated homocysteinase which has the amino acid sequence of SEQ. ID No. 10 or variant thereof having desulfurase activity to homocysteine as a substrate at least 100 times greater than that to cysteine as a substrate when said substrates are present in a physiological fluid. 10. The homocysteinase of claim 9 which has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas, or a mutated form thereof.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

Mutated form: A homocysteinase which is at least about 70%, more preferably 80%, and most preferably 90% homologous with a homocysteinase that occurs in nature and has been identified in a particular organism. Support in Specification: `762 Col. 6, 51-58

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Claim Language `762 Patent 11. The homocysteinase of claim 9 which further comprises at least one histidine residue at the Nterminus. 12. A purified and isolated homocysteinase which has at least about 110% of the activity of the homocysteinase of SEQ ID No. 10 toward homocysteine and no more than about 90% of the activity of the homocysteinase of SEQ ID No. 10 toward cysteine or methionine in a suitable assay. 13. The homocysteinase of claim 12 which has the amino acid sequence of a desulfurase derived from Pseudomonas, Clostridium, Aeromonas or Trichomonas, or a mutated form thereof. 14. The homocysteinase of claim 12 which further comprises at least one histidine residue at the Nterminus.

Agreed Proposed Claim Construction See above

AntiCancer's Proposed Construction

Defendant's Proposed Construction

Court's Construction

See above

See above

See above

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Dated: July 11, 2008

CERTIFICATE OF SERVICE I hereby certify that a copy of the foregoing JOINT CLAIM CONSTRUCTION WORKSHEET was this date served upon all counsel of record by transmission through the Case Management/Electronic Case Filing (CM/ECF) system of the U.S. District Court for the Southern District of California, and that all parties in this case are represented by counsel who are CM/ECF participants.

By: s/Joseph C. Kracht Attorney for Plaintiff AntiCancer, Inc.