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1 Henry C. Su (SBN 211202; [email protected]) Katharine L. Altemus (SBN 227080; [email protected]) 2 HOWREY LLP 1950 University Avenue, 4th Floor 3 East Palo Alto, California 94303 Telephone: (650) 798-3500 4 Facsimile: (650) 798-3600 5 Robert Ruyak Matthew Wolf (Admitted Pro Hac Vice) 6 Marc Cohn (Admitted Pro Hac Vice) HOWREY LLP 7 1299 Pennsylvania Avenue, NW Washington, DC 20004 8 Telephone: (202) 783-0800 Facsimile: (202) 383-6610 9 Attorneys for Plaintiffs 10 HOLOGIC, INC., CYTYC CORPORATION and HOLOGIC L.P. 11 12 13 UNITED STATES DISTRICT COURT NORTHERN DISTRICT OF CALIFORNIA SAN JOSE DIVISION Case No. C08 00133 RMW (RS) DECLARATION OF KATHARINE L. ALTEMUS IN SUPPORT OF PLAINTIFFS' OPENING CLAIM CONSTRUCTION BRIEF (PATENT L.R. 4-5(a)) Markman Hearing Date: June 25, 2008 Time: To Be Set Room: Courtroom 6, 4th Floor Judge: Hon. Ronald M. Whyte
14 HOLOGIC, INC., CYTYC CORPORATION, and HOLOGIC L.P., 15 Plaintiffs, 16 vs. 17 SENORX, INC., 18 Defendant. 19 20 21 AND RELATED COUNTERCLAIMS. 22 23 24 25 26 27 28
Altemus Declaration ISO Construction of Claim Terms Case No. C08 00133 RMW (RS)
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I, Katharine L. Altemus, declare that I am an associate in the law firm of Howrey LLP and a
2 member of the Bar of this court, and I serve as one of the outside counsel for Plaintiffs Hologic, Inc., 3 Cytyc Corporation and Hologic LP. The following declaration is based on my personal knowledge, 4 and if called upon to testify, I could and would competently testify as to the matters set forth herein. 5 1. Attached hereto as Exhibit A is a true and correct copy of United States Patent No.
6 5,913,813. 7 2. Attached hereto as Exhibit B is a true and correct copy of United States Patent No.
8 6,413,204. 9 3. Attached hereto as Exhibit C is a true and correct copy of United States Patent No.
10 6,482,142. 11 4. Attached hereto as Exhibit D is a true and correct copy of Defendant and
12 Counterclaimant Cytyc Corporation's Opening Claim Construction Brief (Pat. L.R. 4-5(a)), filed in 13 Xoft v. Cytyc Corporation, et al., United States District Court, Northern District of California, Case 14 No. CV-05-05312 RMW on November 9, 2006, Docket No. 48. 15 5. Attached hereto as Exhibit E is a true and correct copy of Order Denying Plaintiffs'
16 Motion for Preliminary Injunction (Unredacted Version) Filed Under Seal in the within action on April 17 25, 2008, Docket No. 110. 18 6. Attached hereto as Exhibit F is a true and correct copy of Claim Construction Order,
19 filed in Xoft v. Cytyc Corporation, et al., United States District Court, Northern District of California, 20 Case No. CV-05-05312 RMW on April 27, 2007, Docket No. 109. 21 7. Attached hereto as Exhibit G is a true and correct copy of Plaintiffs' Notice of Motion
22 and Motion for Preliminary Injunction filed under seal in the within action on February 6, 2008, 23 Docket No. 8. 24 8. Attached hereto as Exhibit H is the Declaration of Lynn J. Verhey, Ph.D. In Support Of
25 Plaintiffs' Proposed Construction Of Claim Terms, Phrases And Clauses, with exhibits A, B, and C 26 thereto, signed on May 21, 2008. 27 \\ 28
Altemus Declaration ISO Construction of Claim Terms Case No. C08 00133 RMW (RS) -1-
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9.
Attached hereto as Exhibit I is a true and correct copy of Amendment to Patent
2 Application 08/900,021 dated September 1, 1998, on file with the United States Patent and Trademark 3 Office, and part of the prosecution history of United States Patent No. 5,913,813. 4 10. Attached hereto as Exhibit J is a true and correct copy of Amendment to Patent
5 Application 09/464,727, dated February 27, 2002, on file with the United States Patent and Trademark 6 Office, and part of the prosecution history of United States Patent No. 6,482,142. 7 I declare under penalty of perjury that the foregoing is true and correct.
8 Executed on May 21, 2008 at East Palo Alto, California 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Altemus Declaration ISO Construction of Claim Terms Case No. C08 00133 RMW (RS) -2-
/s/ Katharine L. Altemus
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EXHIBIT A
111111111111111111111111111111111111111111111111111111111111111111111111111
Case 5:08-cv-00133-RMW
United States Patent
Williams et al.
[54] [75]
US005913813A Document 135-2 Filed 05/21/2008 Page 2 of 7 [19] [11] Patent Number: 5,913,813 [45] Date of Patent: Jun. 22, 1999
5,106,360 5,429,582 5,611,767 5,662,580 5,782,742 5,785,688 4/1992 7/1995 3/1997 9/1997 7/1998 7/1998 Ishiwara et al. . Williams. Williams. Bradshaw et al. Crocker et al. . Joshi et al. .
DOUBLE-WALL BALLOON CATHETER FOR TREATMENT OF PROLIFERATIVE TISSUE Inventors: Jeffery A. Williams, Baltimore, Md.; Christopher H. Porter, Woodinville, Wash.; Jeffrey F. Williamson; James F. Dempsey, both of S1. Louis, Mo.; Timothy J. Patrick; James B. Stubbs, both of Alpharetta, Ga. Assignee: Proxima Therapeutics, Inc., Alpharetta, Ga. Appl. No.: 08/900,021 Filed:
6
600/3
Primary Examiner-John P. Lacyk Attorney, Agent, or Firm-Nikolai, Mersereau & Dietz, PA.
[57] ABSTRACT
[73]
[21] [22] [51] [52] [58] [56]
Jul. 24, 1997 A61N 5/00 600/3 600/1-8
Int. Cl. U.S. Cl. Field of Search References Cited U.S. PATENT DOCUMENTS 3,324,847 6/1967 Zoumboulis.
An instrument for use in brachytherapy comprises a concentric arrangement of inner and outer distensible, spherical chambers disposed near the proximal end of a catheter body where one of the chambers is made to contain a radioactive material with the other chamber containing a radiation absorptive material, the apparatus functioning to provide a more uniform absorbed dose profile in tissue surrounding a cavity created by the removal of a tumor. An alternative embodiment includes non-spherical inner and outer chambers whose respective walls are spaced equidistant over the entire surfaces thereof. 13 Claims, 2 Drawing Sheets
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DOUBLE-WALL BALLOON CATHETER FOR TREATMENT OF PROLIFERATIVE TISSUE BACKGROUND OF THE INVENTION
outer chamber. Where the core contains the absorbent material, the radial depth of penetration of the radiation can be tailored by controlling the core size.
DESCRIPTION OF THE DRAWINGS 5 I. Field of the Invention The foregoing features, objects and advantages of the This invention relates generally to apparatus for use in invention will become apparent to those skilled in the art treating proliferative tissue disorders, and more particularly from the following detailed description of a preferred to an apparatus for the treatment of such disorders in the embodiment, especially when considered in conjunction body by the application of radioactive material and/or radia- 10 with the accompanying drawings in which: tion emissions. FIG. 1 is a side view of an apparatus for delivering II. Discussion of the Prior Art radioactive emissions to body tissue; In the Williams U.S. Pat. No. 5,429,582 entitled "Tumor FIG. 2 is a cross-sectional view taken along the line 2-2 Treatment", there is described a method and apparatus for 15 in FIG. 1; treating tissue surrounding a surgically excised tumor with FIG. 3 is a fragmentary side view of an apparatus for radioactive emissions to kill any cancer cells that may be administering radiation therapy in accordance with a second present in the margins surrounding the excised tumor. In embodiment; accordance with that patent, there is provided a catheter FIG. 4 is a graph helpful in understanding the operation having an inflatable balloon at a distal end thereof to define a distensible reservoir. Following surgical removal of a 20 of the apparatus of the present invention; and tumor, say in the brain or breast, the deflated balloon may be FIG. 5 depicts a further embodiment of the invention. introduced into the surgically-created pocket left following DESCRIPTION OF THE PREFERRED removal of a tumor and then the balloon is inflated by EMBODIMENT injecting a fluid having radionuclide(s) therein into the 25 distensible reservoir, via a lumen in the catheter. Referring first to FIG. 1, there is indicated generally by numeral 10 a surgical instrument for providing radiation When it is considered that the absorbed dose rate at a treatment to proliferative tissue in a living patient. It is seen point exterior to the radioactive source is inversely proporto comprise a tubular body member 12 having first and tional to the square of the distance between the radiation second lumens 14 and 16 (FIG. 2) extending from proximal source and the target point, tissue directly adjacent the wall of the distensible reservoir may be overly "hot" to the point 30 ports 18 and 20 in a molded plastic hub 22 to inflation ports where healthy tissue necrosis may result. In general, the 24 and 26 formed through the side wall of the tube 12 and amount of radiation desired by the physician is a certain intersecting with the lumens 14 and 16, respectively. minimum amount that is delivered to a site 0-3 ems away Affixed to the tubular body 12 proximate the distal end 28 from the wall of the excised tumor. It is desirable to keep the thereof is an inner spatial volume 30 which may be defined radiation in the space between that site and the wall of the 35 by a generally spherical polymeric film wall 32. The interior distensible reservoir as uniform as possible to prevent overof the chamber 30 is in fluid communication with the exposure to tissue at or near the reservoir wall. In treating inflation port 26. Surrounding the spatial volume 30 is an other cancers, such as bladder cancer, where the neoplastic outer chamber 34 defined by an outer polymeric film wall 36 tissue is generally located on the bladder surface, deep that is appropriately spaced from the wall 32 of the inner 40 chamber 30 when the two chambers are inflated or otherwise penetration is unnecessary and to be avoided. filled and supported. Chamber 34 encompasses the inflation A need exists for an instrument which may be used to port 24. deliver radiation from a radioactive source to target tissue within the human body of a desired intensity and at a The embodiment of FIG. 1 can be particularly described predetermined distance from the radiation source without 45 as comprising two spherical chambers 30 and 34, one inside over-exposure of body tissues disposed between the radiathe other. In accordance with a first embodiment of the tion source and the target. invention, the outer chamber 34, being the volume defined by the space between the inner spherical wall 32 and the SUMMARY OF THE INVENTION outer spherical wall 36, may be filled with air or, We have found that it is possible to deliver a desired 50 alternatively, a radiation absorbing fluid, such as a contrast media used in angiography. The inner chamber 30 is then radiation dose at a predetermined radial distance from a filled with a material containing a predetermined source of radioactivity by providing a first spacial volume at radionuclide, for example, 1-125, 1-131, Yb-169 or other the distal end of a catheter and a second spacial volume source of radiation, such as radio nuclides that emit photons, defined by a surrounding of the first spatial volume by a polymeric film wall where the distance from the spatial 55 beta particles or other therapeutic rays. Those skilled in the art will appreciate that instead of volume and the wall is maintained substantially constant having the inner spatial volume 30 defined by a generally over their entire surfaces. One of the inner and outer spherical polymeric film wall as at 32, the catheter body volumes is filled with either a fluid or a solid containing a member 12 may have a solid spherical radiation emitting radionuclide(s) while the other of the two volumes is made to contain either a low radiation absorbing material, e.g., air 60 material in which event that solid sphere would be surrounded with the outer spherical wall 36 with the spatial or even a more absorptive material, such as an x-ray contrast volume therebetween occupied by a radioactive ray absorfluid. Where the radioactive material comprises the core, the bent material, such as air, water or a contrast material. surrounding radiation absorbing material serves to control It is further contemplated that instead of having the inner the radial profile of the radioactive emissions from the particular one of the inner and outer volumes containing the 65 spatial volume comprising a single solid sphere, it may instead comprise a plurality of radioactive particles strateradionuclide(s) so as to provide a more radially uniform gically placed within the inner spatial volume so as to radiate radiation dosage in a predetermined volume surrounding the
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in all directions with a substantially equal intensity. FIG. 5 illustrates a catheter having the inner spatial volume occupied by a plurality of radioactive beads that are mounted on the distal ends of a plurality of wires that are routed through the catheter body and exit a plurality of ports formed through the wall of the catheter body and reaching the lumen. This arrangement allows the exact positioning of the individual radiation sources to be positioned so as to generate a desired resultant profile. It is not essential to the invention that the chambers 30 and 34 have spherical walls, so long as the spacing between the wall of the inner chamber and the wall of the outer chamber remain generally constant, such as is illustrated in FIG. 3. Referring to FIG. 4, there is shown the two concentric spherical chambers of FIG. 1 defined by inner spherical wall 32 and outer spherical wall 36 disposed within the margin 38 of a surgically excised tumor. It is desired that the radiation emitted from the core 32 be capable of delivering a certain minimum dose absorbed at a location approximately 0-3 ems from the margin 38. Curve 40 is a plot of absorbed dose vs. radial distance that would be obtained if the inner chamber defined by spherical wall 32 was not present and the entire volume of the spherical chamber defined by wall 36 were filled with the radioactive fluid. Plot 42 reflects the absorbed dose distribution as a function of radial distance when the radioactive fluid is contained within the inner chamber and is surrounded by either a gas or a more radiation absorbing material. Comparing the plots 40 and 42, by providing the concentric arrangement depicted, the absorbed dose profile in the space between the 2 em site and the wall of the outer balloon is maintained much more uniform, thus preventing over-treatment of body tissue at or close to the outer wall 36 of the instrument. That is to say, to obtain the same end point absorbed dose at 2 ern, it would be necessary to increase the source activity relative to that used for a completely filled (to surface 36) configuration, assuming the same radionuclide is used in both configurations. With no limitation intended, the distensible polymeric chambers may comprise a biocompatible, radiation resistant polymer, such as Silastic rubbers, polyurethanes, polyethylene, polypropylene, polyester, PVC, C-Flex. The radioactive fluid contained within the inner chamber 32 can be made from any solution of radionuclide(s), e.g., a solution of 1-125 or 1-131. A radioactive fluid can also be produced using a slurry of a suitable fluid containing small particles of solid radionuclides, such as Au-198, Y-90. Moreover, the radionuclide(s) can be embodied in a gel. In the embodiments heretofore described, the material containing the radionuclide(s) is located in the inner chamber. The invention also contemplates that the outer chamber 34 may contain the material having the radionuclide therein while the inner chamber 30 contains the radiation absorptive material. This configuration is advantageous where a profile exhibiting higher intensity at a tissue surface with lesser penetration is desired. By using this approach, less volume of radioactive material is required than if the entire volume of the device were filled with radioactive material. Moreover, the outer chamber wall need not be spherical, yet a uniform profile is obtainable. Experiments have shown that a steeper radial absorbed source gradient can be obtained using a radiation attenuation fluid in the inner chamber 30 than otherwise obtains when only a single distensible chamber is used, as in the aforereferenced Williams U.S. Pat. No. 5,429,582. The invention also contemplates that the radioactive material in the inner core can be replaced by a core containing solid radio nuclide-containing
particles. For example, radioactive micro spheres of the type available from the 3M Company of St. Paul, Minn., may be used in place of the fluid. This radioactive source can either be preloaded into the catheter at the time of manufacture or 5 loaded into the device after it has been implanted into the space formerly occupied by the excised tumor. Such a solid radioactive core configuration offers the advantage in that it allows a wider range of radio nuclides than if one is limited to liquids. Solid radio nuclides that could be used with the 10 delivery device of the present invention are currently generally available as brachytherapy radiation sources. In either the concentric spherical embodiment of FIG. lor the non-spherical configuration of FIG. 3, the spacing 15 between the inner and outer chambers needs to be held somewhat constant to avoid "hot spots". This result can be achieved by careful placement of precision blown polymer parisons or by using compressible foams or mechanical spacers in the form of webs joining the inner wall 32 to the 20 outer wall 36. This invention has been described herein in considerable detail in order to comply with the patent statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use such 25 specialized components as are required. However, it is to be understood that the invention can be carried out by specifically different equipment and devices, and that various modifications, both as to the equipment and operating procedures, can be accomplished without departing from the 30 scope of the invention itself. What is claimed is: 1. Apparatus for delivering radioactive emissions to a body location with a uniform radiation profile, comprising:
35
40
45
50
55
60
65
(a) a catheter body member having a proximal end and distal end; (b) an inner spatial volume disposed proximate the distal end of the catheter body member; (c) an outer, closed, inflatable, chamber defined by a radiation transparent wall affixed to the body member proximate the distal end thereof in surrounding relation to the inner spatial volume with a predetermined constant spacing between said inner spatial volume and the radiation transparent wall; (d) a material containing a radionuclide(s) disposed in one of the inner spatial volume and outer chamber; and (e) means disposed in the other of the inner spatial volume and outer chamber for rendering uniform the radial absorbed dose profile of the emissions from the one of the inner spatial volume and outer chamber containing the radio nuclides. 2. The apparatus as in claim 1 wherein said inner spatial volume is an inner closed, chamber defined by a further radiation transparent wall. 3. The apparatus of claim 1 wherein the means for rendering uniform the absorbed dose profile is a radiation attenuating material. 4. The apparatus of claim 3 wherein the radiation attenuating material is selected from a group consisting of barium sulphate, water, and X-ray contrast media. 5. The apparatus as in claim 2 wherein the radio nuclide is in a fluid form. 6. The apparatus as in claim 5 wherein the fluid comprises an isotope of iodine. 7. The apparatus as in claim 1 wherein the radio nuclide is a slurry of a fluid containing particles of a solid isotope.
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12. The apparatus as in claim 1 wherein the material 8. The apparatus as in claim 2 wherein the inner chamber containing a radionuclide comprises a plurality of radioaccontains the radioactive material. tive solid particles placed at predetermined locations within 9. The apparatus as in claim 1 wherein the outer chamber the inner spatial volume to provide a desired composite contains the radioactive material. radiation profile. 10. The apparatus as in claim 8 wherein the radioactive 5 13. The apparatus as in claim 2 wherein the inner and material is a fluid. outer chambers are spherical in shape and are concentric. 11. The apparatus as in claim 8 wherein the radioactive material is a solid.
* * * * *
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(12)
111111111111111111111111111111111111111111111111111111111111111111111111111 US006413204Bl Document 135-3 Filed 05/21/2008 Page 2 of 12
(10)
(45)
United States Patent
Winkler et al.
Patent No.: US 6,413,204 Bl Date of Patent: *Jul. 2, 2002
(54)
INTERSTITIAL BRACHYTHERAPY APPARATUS AND METHOD FOR TREATMENT OF PROLIFERATIVE TISSUE DISEASES Inventors: Rance A. Winkler, Atlanta; Timothy J. Patrick; James Stubbs, both of Alpharetta, all of GA (US) Assignee: Proxima Therapeutics, Inc., Alpharetta, GA (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. This patent is subject to a terminal disclaimer.
EP
GB
(75)
WO WO WO WO WO WO WO
0867200 2105201 9210932 9309724 9719723 9812979 9911325 9933515 9942163
9/1998 3/1983 7/1992 5/1993 6/1997 4/1998 3/1999 7/1999 9/1999
............ A6IN/1/06 ............ A6IN/5/02 ........... A6IB/17/36 ............ A6IN/5/oo ........... A6IB/19/oo
(73)
OTHER PUBLICATIONS A. Bex et al., A System for Focal Intracavitary Irradiation of Bladder Cancer with Remote Iridium-192 Afterloading, 21 Eur Urol 1992, 245-249 (1992). Ashpole, R.D. et al., "A New Technique of Brachtherapy for Malignant Gliomas with Caesium-137: A New Method Utilizing a Remote Afterloading System," Clinical Oncology, vol. 2, 333-7 (1990). Chun, M. et al., "Interstitial Iridium-192 Implantation for Malignant Brain Tumours. Part II: Clinical Experience," The British Journal of Radiology, vol. 62, 158-62 (1989). Garfield, J. et al., "Postoperative Intracavitary Chemotherapy of Malignant Gliomas," J. Neurosurg., vol. 39, 315-22 (Sep. 1973). (List continued on next page.)
( *)
(21) (22)
Appl. No.: 09/293,524 Filed: Apr. 15, 1999 Related U.S. Application Data
(63)
Continuation-in-part of application No. 08/900,021, filed on Jul. 4, 1997, now Pat. No. 5,913,813.
(51) (52) (58) (56)
Int. CI? U.S. Cl. Field of Search References Cited U.S. PATENT DOCUMENTS
3,324,847 3,872,856 4,417,576 4,706,652 4,754,745 4,763,642 A A A A A A 6/1967 3/1975 11/1983 11/1987 7/1988 8/1988 Zoumboulis .. Clayton Baran Horowitz Horowitz Horowitz
A61N 5/00 600/3 600/1-8
Primary Examiner-John P. Lacyk (74) Attorney, Agent, or Firm-Thomas J. Engellenner; Ronald E. Cahill; Nutter, McClennen & Fish, LLP
(57) ABSTRACT
128/1.2 128/1.2 128/207.15 128/1.2 128/1.2 128/1.2
(List continued on next page.) FOREIGN PATENT DOCUMENTS
An interstitial brachytherapy apparatus for delivering radioactive emissions to an internal body location includes a catheter body member having a proximal end and distal end, an inner spatial volume disposed proximate to the distal end of the catheter body member, an outer spatial volume defined by an expandable surface element disposed proximate to the distal end of the body member in a surrounding relation to the inner spatial volume, and a radiation source disposed in the inner spatial volume.
36 Claims, 3 Drawing Sheets
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0340881
11/1989
A6IN/5/1O
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U.S. PATENT DOCUMENTS
4,821,725 4,867,741 5,084,001 5,084,015 5,106,360 5,112,303 5,152,747 5,236,410 5,429,582 5,484,384 5,503,613 5,566,221 5,611,767 5,662,580 5,707,332 5,713,828 5,720,717 5,764,723 5,782,742 5,785,688 5,913,813 5,924,973 6,036,631 A A A A A A A A A A A A A A A A A A A A A A A 4/1989 9/1989 1/1992 1/1992 4/1992 5/1992 10/1992 8/1993 7/1995 1/1996 4/1996 10/1996 3/1997 9/1997 1/1998 2/1998 2/1998 6/1998 7/1998 7/1998 6/1999 7/1999 3/2000
6,059,812 A 128/420 A 604/10 600/3 604/96 600/2 604/49 604/93 600/12 600/2 600/3 600/3 378/145 600/2 600/3 600/3 600/7 604/21 378/65 600/3 604/141 600/3 600/3 600/3
* 5/2000 Clerc et al.
600/3
* *
Azam et al. Portnoy... Van't Hooft et al. Moriuchi Ishiwara et al. Pudenz et al. Olivier ...... Granov et al. Williams Fearnot Weinberger Smith et al. Williams Bradshaw et al. Weinberger Coniglione D'Andrea .. Weinberger et al. Crocker et al. Joshi et al. Williams et al. Wenberger McGrath et al.
OTHER PUBLICATIONS Gutin, P. et al., "Brachytherapy of Recurrent Malignant Brain Tumors With Removable High-Activity Iodine-125 Sources," J. Neurosurg., vol. 60, 61-8 (1984). Johannesen, T.B. et al., "Intracavity Fractionated Balloon Brachytherapy in Gilioblastoma," Aeta Neuroehir (Wien), vol. 141, 127-33 (1999). Leibel, S. et al., "The Integration of Interstitial Implantation Into the Preliminary Mangement of Patients With Malignant Gliomas: Results of a Phase II Northern California Oncology Group Trial," Am. J. Clin. Oneol. (CCl), vol. 10, No.2, p. 106 (1987).* Roberts, D. et al., "Interstitial Hyperthermia and Iridium Brachytherapy in Treamtnet of Malignant Glioma," J. Neurosurg., vol. 64,581-7 (1986).* Wu, A. et al., "Interstitial Iridium-192 Implantation for Malignant Brain Tumours, Part 1: Techniques of Dosimetry Planning," The British J ournal ofRadiology, vol. 62, 154-7 (1989).* * cited by examiner
u.s. Patent
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28
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32 26
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FIG.7A
FIG.7B
FIG.7C
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A
B
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DISTANCE FROM SURFACE OF OUTER VOLUME
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distensible reservoir. Following surgical removal of a tumor, the surgeon introduces the balloon catheter into the surgically created pocket left following removal of the tumor. The balloon is then inflated by injecting a fluid having one or 5 more radio nuclides into the distensible reservoir via a lumen CROSS-REFERENCE TO RELATED in the catheter. APPLICATIONS The apparatus described in Williams solves some of the problems found when using radioactive seeds for interstitial This application is a continuation-in-part of U.S. patent brachytherapy, but leaves some problems unresolved. The application Ser. No. 08/900,021, filed Jul. 24, 1997, now U.S. Pat. No. 5,913,813 the contents of which are specifi- 10 absorbed dose rate at a target point exterior to a radioactive source is inversely proportional to the square of the distance cally incorporated herein by reference. between the radiation source and the target point. As a result, BACKGROUND OF THE INVENTION where the radioactive source has sufficient activity to deliver a prescribed dose, say 2 centimeters into the target tissue, the The invention relates generally to apparatus for use in treating proliferative tissue disorders, and more particularly 15 tissue directly adjacent the wall of the distensible reservoir, where the distance to the radioactive source is very small, to an apparatus for the treatment of such disorders in the may still be overly "hot" to the point where healthy tissue body by the application of radiation. necrosis may result. In general, the amount of radiation Malignant tumors are often treated by surgical resection desired by the physician is a certain minimum amount that of the tumor to remove as much of the tumor as possible. 20 is delivered to a region up to about two centimeters away Infiltration of the tumor cells into normal tissue surrounding from the wall of the excised tumor. It is desirable to keep the the tumor, however, can limit the therapeutic value of radiation that is delivered to the tissue in the target treatment surgical resection because the infiltration can be difficult or region within a narrow absorbed dose range to prevent impossible to treat surgically. Radiation therapy can be used over-exposure to tissue at or near the reservoir wall, while to supplement surgical resection by targeting the residual 25 still delivering the minimum prescribed dose at the maxitumor margin after resection, with the goal of reducing its mum prescribed distance from the reservoir wall. size or stabilizing it. Radiation therapy can be administered There is still a need for an instrument which can be used through one of several methods, or a combination of to deliver radiation from a radioactive source to target tissue methods, including external-beam radiation, stereotactic within the human body with a desired intensity and at a radiosurgery, and permanent or temporary interstitial brachytherapy. The term "brachytherapy," as used herein, 30 predetermined distance from the radiation source without over-exposure of body tissues disposed between the radiarefers to radiation therapy delivered by a spatially confined tion source and the target. radioactive material inserted into the body at or near a tumor or other proliferative tissue disease site. Owing to the SUMMARY OF THE INVENTION proximity of the radiation source, brachytherapy offers the 35 advantage of delivering a more localized dose to the target The present invention solves the problems described tissue region. above by providing an interstitial brachytherapy apparatus For example, brachytherapy is performed by implanting for delivering radioactive emissions to an internal body radiation sources directly into the tissue to be treated. location. The apparatus includes a catheter body member Brachytherapy is most appropriate where 1) malignant 40 having a proximal end and distal end, an inner spatial tumor regrowth occurs locally, within 2 or 3 em of the volume disposed proximate to the distal end of the catheter original boundary of the primary tumor site; 2) radiation body member, an outer spatial volume defined by an expandtherapy is a proven treatment for controlling the growth of able surface element disposed proximate to the distal end of the malignant tumor; and 3) there is a radiation dosethe body member in a surrounding relation to the inner response relationship for the malignant tumor, but the dose 45 spatial volume, and a radiation source disposed in the inner that can be given safely with conventional external beam spatial volume. The inner and outer spatial volumes are radiotherapy is limited by the tolerance or normal tissue. In configured to provide an absorbed dose within a predeterbrachytherapy, radiation doses are highest in close proximity mined range throughout a target tissue. The target tissue is to the radiotherapeutic source, providing a high tumor dose located between the outer spatial volume expandable surface while sparing surrounding normal tissue. Interstitial brachy- 50 and a minimum distance outward from the outer spatial therapy is useful for treating malignant brain and breast volume expandable surface. The predetermined dose range tumors, among others. is defined as being between a minimum prescribed absorbed dose for delivering therapeutic effects to tissue that may Interstitial brachytherapy is traditionally carried out using include cancer cells, and a maximum prescribed absorbed radioactive seeds such as 1251 seeds. These seeds, however, produce inhomogeneous dose distributions. In order to 55 dose above which healthy tissue necrosis may result. achieve a minimum prescribed dosage throughout a target In different embodiments, the inner spatial volume can be region of tissue, high activity seeds must be used, resulting defined by a distensible polymeric wall containing radioacin very high doses being delivered in some regions in tive source material which can be a fluid material, by a solid proximity to the seed or seeds which can cause radionecrosis radioactive source, or by a region containing a plurality of in healthy tissue. 60 solid radioactive sources. The outer spatial volume is Williams U.S. Pat. No. 5,429,582, entitled "Tumor defined by an expandable surface element that may be, for example, an inflatable polymeric wall or an expandable Treatment," describes a method and apparatus for treating cage. The expandable surface element can cause tissue to tissue surrounding a surgically excised tumor with radioacconform to its intended shape, and preferably, the apparatus tive emissions to kill any cancer cells that may be present in the tissue surrounding the excised tumor. In order to imp le- 65 creates absorbed isodose profiles in the target tissue that are substantially similar in shape to the expandable surface ment the radioactive emissions, Williams provides a catheter element in substantially three dimensions. having an inflatable balloon at its distal end that defines a INTERSTITIAL BRACHYTHERAPY APPARATUS AND METHOD FOR TREATMENT OF PROLIFERATIVE TISSUE DISEASES
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The invention also provides a method for treating a tion resistant polymer, such as silas tic rubbers, polyurethanes, polyethylene, polypropylene, polyester, or proliferating tissue disease using interstitial brachytherapy PVc. at an internal body location. The method includes surgically The embodiment of FIG. 1 includes inner and outer creating access to the proliferating tissue within a patient and surgically resecting at least a portion of the proliferating 5 spatial volumes 30 and 34, one inside the other. The outer spatial volume 34, being the volume defined by the space tissue to create a resection cavity within body tissue. An between the inner spherical wall 32 and the outer spherical interstitial brachytherapy apparatus for delivering radioacwall 36, may be filled with air or, alternatively, a radiation tive emissions as described above is then provided and absorbing fluid, such as a contrast media used in angiograintra-operatively placed into the resection cavity. After a prescribed absorbed dose has been delivered to tissue sur- 10 phy. The inner volume 30 is then filled with a material containing a predetermined radionuclide, for example, rounding the apparatus, the apparatus is removed. The 1-125, 1-131, Yb-169 or other source of radiation, such as radioactive source material may be placed into the interstiradio nuclides that emit photons, beta particles, gamma tial brachytherapy apparatus after the apparatus is placed in radiation, or other therapeutic rays. The radioactive material the resection cavity, and may be removed before the appacontained within the inner chamber 32 can be a fluid made ratus is removed. The method has particular applications to 15 from any solution ofradionuclide(s), e.g., a solution ofI-125 brain and breast cancers. or 1-131. A radioactive fluid can also be produced using a slurry of a suitable fluid containing small particles of solid DESCRIPTION OF THE DRAWINGS radionuclides, such as Au-198, Y-90. Moreover, the radionuclide(s) can be embodied in a gel. One radioactive The foregoing features, objects and advantages of the invention will become apparent to those skilled in the art 20 material useful in the invention is Iotrex?", a sterile single use, non-pyrogenic solution containing sodium 3-C 2 51)iodofrom the following detailed description of a preferred 4-hydroxybenzenesulfonate C 2 51-HBS), available from embodiment, especially when considered in conjunction Proxima Therapuetics, Inc. of Alpharetta, Ga. with the accompanying drawings in which: As an alternative method of providing radioactive source FIG. 1 is a side view of an interstitial brachytherapy 25 material, such material may be coated on, chemically apparatus of the invention for delivering radioactive emisbonded to, or copolymerized with the material forming inner sions to body tissue; spherical wall 32. FIG. 2 is a cross-sectional view taken along the line 2-2 Where the radioactive source material is provided as a in FIG. 1; fluid or gel within inner spherical wall 32, it may be FIG. 3 is an additional embodiment of an interstitial 30 desirable to provide a solid outer spherical wall 36. Should inner spherical wall 32 rupture, the radioactive source matebrachytherapy apparatus of the invention having a solid rial will be retained within outer spherical wall 36 and will radiation source; not leak into the patient. For further safety, the burst strength FIG. 4 is an additional embodiment of an interstitial of inner spherical wall 32 may be designed so as to be lower brachytherapy apparatus of the invention having a radiation 35 than that of outer spherical wall 36. In this way, inner source comprising a plurality of solid radiation particles; spherical wall 32 will rupture under stress first, releasing its FIG. 5 depicts a further embodiment of the invention contents into the larger combined space of the inner and wherein the inner and outer spatial volumes of the interstitial outer volumes 30, 34 and releasing any pressure built up brachytherapy apparatus are non-spherical; within the inner spherical wall 32 and reducing the risk that FIG. 6 illustrates an interstitial brachytherapy apparatus 40 radioactive material will spill into the patient. In the event of of the invention having an expandable outer spatial volume such a rupture, radioactive fluid could be drained from the surface; and apparatus through port 24 by way of lumen 14, and also from FIGS. 7A-D illustrate the absorbed dose versus distance port 26 by way of lumen 16. into target tissue for several interstitial brachytherapy appaIn a further embodiment, illustrated in FIG. 3, instead of ratus configurations. 45 having the inner spatial volume 30 defined by a generally spherical polymeric film wall as at 32, the catheter body DESCRIPTION OF THE PREFERRED member 12 may have a solid spherical radiation emitting EMBODIMENT material 44 as the inner spatial volume 30. For example, A surgical instrument 10 for providing radiation treatment radioactive micro spheres of the type available from the 3M to proliferative tissue in a living patient is illustrated in FIG. 50 Company of St. Paul, Minn., may be used. This radioactive 1. Surgical instrument 10 includes a tubular body member source can either be preloaded into the catheter at the time 12 having first and second lumens 14 and 16 (FIG. 2) of manufacture or loaded into the device after it has been extending from proximal ports 18 and 20 in a molded plastic implanted into the space formerly occupied by the excised hub 22 to inflation ports 24 and 26 formed through the side tumor. The solid radiation emitting material 44 can be wall of the tube 12 and intersecting with the lumens 14 and 55 inserted through catheter 12 on a wire 46, for example, using 16, respectively. an afterloader (not shown). Such a solid radioactive core Affixed to the tubular body 12 proximate the distal end 28 configuration offers an advantage in that it allows a wider range of radionuclides than if one is limited to liquids. Solid thereof is an inner spatial volume 30 which may be defined radio nuclides that could be used with the delivery device of by a generally spherical polymeric film wall 32. The interior of the inner volume 30 is in fluid communication with the 60 the present invention are currently generally available as inflation port 26. Surrounding inner spatial volume 30 is an brachytherapy radiation sources. In this embodiment solid outer spatial volume 34 defined by an outer polymeric film spherical inner spatial volume 30 is surrounded by outer wall 36 that is appropriately spaced from the wall 32 of the spherical wall 36, defining outer spatial volume 34 between inner spatial volume 30 when the two volumes are inflated the outer spherical wall 36 and the inner spatial volume 30 or otherwise supported. Outer volume 34 encompasses 65 with the outer spatial volume 34 occupied by a radioactive inflation port 24. With no limitation intended, the distensible ray absorbent material, such as air, water or a contrast polymeric film walls may comprise a biocompatible, radiamaterial.
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In a further embodiment, illustrated in FIG. 4, inner prescribed dose within target tissue while avoiding necrosis spatial volume 30, instead of comprising a single solid inducing radiation "hot spots" in tissue proximate to the sphere, may comprise a plurality of radiation emitting parapparatus. FIG. 7A illustrates an interstitial brachytherapy ticles 44 strategically placed within the inner spatial volume apparatus (device A) such as those employed in U.S. Pat. 30 so as to radiate in all directions with a substantially equal 5 No. 5,429,582, having a single spatial volume 50 filled with intensity. This plurality of radiation emitting particles 44 can a radioactive material in solution. FIG. 7B illustrates an be mounted on the distal ends of a plurality of wires 46 that interstitial brachytherapy apparatus (device B) of the invention having a first, inner spatial volume 30 filled with a are routed through the catheter body 12 and exit a plurality radioactive material in solution and defined by membrane of ports formed through the wall of the catheter body and reaching the lumen. This arrangement allows the exact 10 32, and a second, outer spatial volume 34 defined by membrane 36 that is substantially evenly spaced apart from positioning of the individual radiation sources 44 to be membrane 32 in substantially three dimensions. FIG. 7C positioned so as to generate a desired resultant profile. illustrates an additional interstitial brachytherapy apparatus As illustrated in FIG. 5, it is not essential to the invention (device C) of the invention having a solid, spherical radiathat the volumes 30 and 34 have spherical walls, so long as the resultant dosing profile is consistent with the shape of the 15 tion source 44 as the inner spatial volume and a spherical outer spatial volume 34 defined by membrane 36. outer volume 34. That is, the absorbed dose within the target Each of the devices illustrated in FIGS. 7A-C can be tissue at points equidistant from the surface 36 of the outer configured to deliver a substantially uniform dose at a given spatial volume 34 should be substantially uniform in subdistance into the target tissue from the surface of the outer stantially every direction. Put another way, the three dimensional isodose profiles generated by the radiation source 20 spatial volume 34 (or from single spatial volume 50 for device A) and to deliver a minimum prescribed dose within should be substantially similar in shape to the outer spatial a given prescribed depth range into the tissue from the volume 34. Where the inner and outer spatial volumes are surface of the outer spatial volume 34. However, the differcreated by inflatable membranes and one of the volumes ent devices provide very different dose profiles as a function contains a fluid radiation source, this can be achieved by ensuring that the spacing between the wall of the inner 25 of distance from the surface of the outer volume as illustrated in FIG. 7D. FIG. 7D plots the absorbed dose at a given volume and the wall of the outer volume remain generally distance into the target tissue from the surface of the outer constant. In either the concentric spherical embodiment of spatial volume 34 for each of the devices A, B, and C. FIG. 1 or the non-spherical configuration of FIG. 5, this result can be achieved by careful placement of precision Each device can deliver a minimum prescribed dose 52 at blown or molded polymer partitions or by using compress- 30 a given distance from the surface of the outer spatial volume. ible foams or mechanical spacers in the form of webs joining For example, device A can readily be configured to provide the inner wall 32 to the outer wall 36. The desired isodose a dose in a therapeutic range, say between 40 to 60 Gray, at profiles conforming to the shape of the outer spatial volume a distance between 0.5 and 1.0 em from the outer spatial 34 can also be obtained, for example, by strategic placement volume for an outer spatial volume having a diameter of 4.0 of a plurality of radioactive particle sources within the inner 35 em and being in contact with the resection cavity wall. In a spatial volume 30. Where the apparatus of the invention is typical embodiment, the radioactive source material ranges deployed in soft tissue, it may also be important for the from approximately 150 to 450 mCi in activity and encomsurface 36 of the outer spatial volume 34 to be sufficiently passes most of the target treatment area with a 0.4 to 0.6 firm so as to force the target tissue to take on the shape of Gray/hour isodose contour. At this treatment rate, treatment the surface 36 so that the desired relationship between the 40 may be completed in approximately 3 to 7 days, or more isodose profiles and the target tissue is achieved. commonly, in approximately 3 to 5 days. When used in an interstitial application, the surface of the In order to reach the minimum prescribed dosage at this outer spatial volume 34 must establish a relationship distance, however, device A must provide a dose proximate between the inner spatial volume 30 and the target tissue so to the surface of the outer spatial volume that is substantially as to achieve the aforementioned isodose profile, however, 45 larger than the minimum prescribed dose. For the 4.0 em the surface of the outer volume need not be a solid material. diameter outer spatial volume example, the absorbed dosage For example, as illustrated in FIG. 6, the surface of the outer would be approximately 131 Gray at the outer spatial volume 34 could be an expandable cage 48 formed from a volume surface. Ideally, radiation therapy should make use shape memory metal, such as nitinol, or a suitable plastic, the inherent difference in radiosensitivity between the tumor such as an expandable polyethylene cage. Such a cage can 50 and the adjacent normal tissues to destroy cancerous tissue be formed in the desired shape to conform to a particular while causing minimal disruption to surrounding normal isodose profile, then be contracted for delivery to the target tissues. At high doses of radiation, however, the percentage site in vivo, then expanded to cause the tissue surrounding of exposed cells that survive treatment decreases with firstthe surgically resected region to take the appropriate shape. order kinetics in proportion to increasing radiation dose. The size of the outer spatial volume 34 generally will 55 With increasing cell death comes increasing risk of necrosis correspond approximately to the amount of tissue resected, or tissue death in healthy tissue that is treated with a high or be slightly larger, allowing the expandable surface of the dose of radiation. Accordingly, it is desirable to keep the outer spatial volume to urge tissue on the surface of the maximum radiation dose delivered by the brachytherapy resected region into the appropriate shape to promote an apparatus as low as possible while still delivering the desired even dose distribution around the outer spatial volume in the 60 therapeutic dose to the desired range of tissue. target tissue. In typical applications, the outer spatial volume Comparing the plots A, B, and C, the absorbed dose has a diameter of approximately 2 to 4 centimeters. In these profile in the space between the 2 em site and the surface of same applications, where the radiation source is provided as the outer spatial volume for the devices of the invention is a fluid within an inner balloon, the inner balloon generally maintained in a much narrower range, preventing overhas a diameter of approximately 0.5 to 3 centimeters. 65 treatment of body tissue at or close to the surface of the outer FIGS. 7A-D illustrate the ability of an interstitial brachyvolume of the device. Because devices Band C provide an outer spatial volume 34 between the radioactive source and therapy apparatus of the invention to deliver a minimum
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delivered, typically for approximately a week or less. The radiation source is then retrieved and the catheter is removed. The radiation treatment may end upon removal of the brachytherapy apparatus, or the brachytherapy may be supplemented by further doses of radiation supplied externally. It will be understood that the foregoing is only illustrative of the principles of the invention, and that various modifications can be made by those skilled in the art without departing from the scope and spirit of the invention. All references cited herein are expressly incorporated by reference in their entirety. What is claimed is: 1. An interstitial brachytherapy apparatus for delivering radioactive emissions to an internal body location comprising: (a) a catheter body member having a proximal end and distal end; (b) an inner spatial volume disposed proximate to the distal end of the catheter body member; (c) an outer spatial volume defined by an expandable surface element disposed proximate to the distal end of the body member in a surrounding relation to the inner spatial volume; and (d) a radiation source disposed in the inner spatial volume and generating a three-dimensional isodose profile that is substantially similar in shape to the expandable surface element. 2. The apparatus of claim 1, wherein the inner and outer spatial volumes are configured to provide a minimum prescribed absorbed dose for delivering therapeutic effects to a target tissue, the target tissue being defined between the outer spatial volume expandable surface and a minimum distance outward from the outer spatial volume expandable surface, the apparatus providing a controlled dose at the outer spatial volume expandable surface to reduce or prevent necrosis in healthy tissue proximate to the expandable surface. 3. The apparatus of claim 2, wherein a predetermined spacing is provided between said inner spatial volume and the expandable surface element. 4. The apparatus of claim 3, wherein the expandable surface element is adapted to contact tissue surrounding a resected cavity and adapted to conform the tissue to the desired shape of the expandable surface element. 5. The apparatus of claim 2, wherein the minimum prescribed absorbed dose is 40 Gray at a distance of at least one centimeter from the expandable surface element. 6. The apparatus of claim 5, wherein the dose rate in at least a portion of the target tissue is between about 0.4 and 0.6 Gray/hour. 7. The apparatus of claim 5, wherein the maximum absorbed dose delivered to the target tissue is less than 100 Gray. 8. The apparatus of claim 2, wherein the outer spatial volume has a diameter between about two and four centimeters. 9. The apparatus of claim 2, wherein the inner spatial volume is an inner closed, distensible chamber defined by a further radiation transparent wall. 10. The apparatus of claim 9, wherein the radioactive source is in a fluid form. 11. The apparatus of claim 10, wherein the expandable surface element is a solid distensible surface and the outer spatial volume is a closed, distensible chamber and the expandable surface element is a radiation transparent wall.
the target tissue, these devices can use hotter radiation sources to reach the minimum prescribed dosage, but take advantage of the distance between the radioactive source and the target tissue provided by the outer spatial volume 34 to reduce or eliminate hot spots in the target tissue. Returning to the 4.0 em diameter outer spatial volume example, if the radiation source is contained within an inner spatial volume, say a solid radioactive sphere such as device C, the absorbed dose profile becomes much different. If the radiation source is configured to provide the same 60 Gray dose at 0.5 em into the target tissue, the absorbed dose at the outer spatial volume surface is only 94 Gray-a significant decrease from the 131 Gray dose for a type A device. In addition, the treatment range for the type C device will be extended under these circumstance as compared to the type A device, delivering a 40 Gray dose beyond 1.0 em into the target tissue and delivering approximately double the dose at 3.0 em into the target tissue. In one embodiment, the inner and outer spatial volumes are configured to control the absorbed dose at the outer spatial volume surface so that the absorbed dose is no greater than about 100 Gray while providing a therapeutic absorbed dose into the target tissue at the desired range. The capability of the apparatus of the invention to deliver absorbed doses deeper into the target tissue than prior interstitial brachytherapy devices while controlling the dose in proximity to the apparatus to reduce or eliminate the risk of healthy tissue necrosis allows for the use of brachytherapy in a greater number of cases. The interstitial brachytherapy apparatus of the invention can be used in the treatment of a variety of malignant tumors, and is especially useful for in the treatment of brain and breast tumors. Many breast cancer patients are candidates for breast conservation surgery, also known as lumpectomy, a procedure that is generally performed on early stage, smaller tumors. Breast conservation surgery is typically followed by postoperative radiation therapy. Studies report that 80% of breast cancer recurrences after conservation surgery occur near the original tumor site, strongly suggesting that a tumor bed "boost" of local radiation to administer a strong direct dose may be effective in killing any remaining cancer and preventing recurrence at the original site. Numerous studies and clinical trials have established equivalence of survival for appropriate patients treated with conservation surgery plus radiation therapy compared to mastectomy. Surgery and radiation therapy are the standard treatments for malignant solid brain tumors. The goal of surgery is to remove as much of the tumor as possible without damaging vital brain tissue. The ability to remove the entire malignant tumor is limited by its tendency to infiltrate adjacent normal tissue. Partial removal reduces the amount of tumor to be treated by radiation therapy and, under some circumstances, helps to relieve symptoms by reducing pressure on the brain. Amethod according to the invention for treating these and other malignancies begins by surgical resection of a tumor site to remove at least a portion of the cancerous tumor and create a resection cavity. Following tumor resection, but prior to closing the surgical site, the surgeon intraoperatively places an interstitial brachytherapy catheter apparatus, having an inner spatial volume and an outer spatial volume as described above but without having the radioactive source material loaded, into the tumor resection cavity. Once the patient has sufficiently recovered from the surgery, the interstitial brachytherapy catheter is loaded with a radiation source. The radioactive source dwells in the catheter until the prescribed dose of radiotherapy is
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12. The apparatus of claim 11, wherein a burst strength of the distensible chamber defining the outer spatial volume is greater than a burst strength of the chamber defining the inner spatial volume. 13. The apparatus of claim 1, wherein the expandable surface element is an expandable cage. 14. The apparatus of claim 13, wherein the expandable cage comprises a shape memory material. 15. The apparatus of claim 14, wherein the expandable cage comprises nitinol. 16. The apparatus of claim 1, wherein the radiation source is a solid radiation source. 17. The apparatus of claim 1, wherein the radiation source is a plurality of solid radiation sources arranged to provide an isodose profile having a shape substantially similar to the shape of the outer spatial volume. 18. The apparatus of claim 2, wherein the prescribed absorbed dose is delivered to the target tissue in substantially three dimensions. 19. A method for treating a proliferating tissue disease using interstitial brachytherapy at an internal body location comprising: (a) surgically creating access to the proliferating tissue in a patient; (b) surgically resecting at least a portion of the proliferating tissue to create a resection cavity within body tissue; (c) providing an interstitial brachytherapy apparatus for delivering radioactive emissions comprising: (i) a catheter body member having a proximal end and distal end; (ii) an inner spatial volume disposed proximate to the distal end of the catheter body member; (iii) an outer spatial volume defined by an expandable surface element disposed proximate to the distal end of the body member in a surrounding relation to the inner spatial volume; and (iv) a radiation source disposed in the inner spatial volume and generating a three-dimensional isodose profile that is substantially similar in shape to the expandable surface element; (d) intraoperatively placing the interstitial brachytherapy apparatus into the resection cavity until a prescribed absorbed dose has been delivered to tissue surrounding the apparatus; and (e) removing the interstitial brachytherapy apparatus. 20. The method of claim 19, further including placing the radioactive source into the interstitial brachytherapy apparatus after the step of placing the apparatus into the tumor resection cavity. 21. The method of claim 19, further including removing the radioactive source from the interstitial brachytherapy apparatus before the step of removing the apparatus. 22. The method of claim 19, wherein the proliferating tissue is a patient's brain. 23. The method of claim 19, wherein the proliferating tissue is a patient's breast. 24. The method of claim 19, further including configuring the inner and outer spatial volumes to provide a minimum prescribed absorbed dose for delivering therapeutic effects to a target tissue, the target tissue being defined between the outer spatial volume expandable surface and a minimum distance outward from the outer spatial volume expandable surface, the apparatus providing a controlled dose at the outer spatial volume expandable surface to reduce or prevent necrosis in healthy tissue proximate to the expandable surface.
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25. The method of claim 24, further including providing a predetermined spacing between said inner spatial volume and the expandable surface element. 26. The method of claim 25, wherein the expandable surface element is adapted to contact tissue surrounding a resected cavity and adapted to conform the tissue to the desired shape of the expandable surface element. 27. The method of claim 24, wherein the minimum prescribed absorbed dose is 40 Gray at a distance of at least one centimeter from the expandable surface element. 28. The method of claim 27, wherein the dose rate in at least a portion of the target tissue is between about 0.4 and 0.6 Gray/hour. 29. The method of claim 27, wherein the maximum absorbed dose delivered to the target tissue is less than 100 Gray. 30. The method of claim 24, wherein the outer spatial volume has a diameter between about two and four centimeters. 31. The method of claim 24, wherein the step of configuring the inner and outer spatial volumes includes expanding the inner and outer spatial volumes. 32. A method for treating a proliferating tissue disease using interstitial brachytherapy at an internal body location comprising: (a) surgically creating access to the proliferating tissue in a patient; (b) surgically resecting at least a portion of the proliferating tissue to create a resection cavity within body tissue; (c) providing an interstitial brachytherapy apparatus for delivering radioactive emissions comprising: (i) a catheter body member having a proximal end and distal end; (ii) an inner spatial volume disposed proximate to the distal end of the catheter body member; (iii) an outer spatial volume defined by an expandable surface element disposed proximate to the distal end of the body member in a surrounding relation to the inner spatial volume; and (iv) a radiation source disposed in the inner spatial volume; (d) intraoperatively placing the interstitial brachytherapy apparatus into the resection cavity; (e) configuring the inner and outer spatial volumes to provide a minimum prescribed absorbed dose for delivering therapeutic effects to a target tissue, the target tissue being defined between the outer spatial volume expandable surface and a minimum distance outward from the outer spatial volume expandable surface, the apparatus providing a controlled dose at the outer spatial volume expandable surface to reduce or prevent necrosis in healthy tissue proximate to the expandable surface; and (t) removing the interstitial brachytherapy apparatus. 33. The method of claim 32, wherein the step of configuring the inner and outer spatial volumes includes expanding the inner and outer spatial volumes. 34. A method for treating a proliferating tissue disease using interstitial brachytherapy at an internal body location comprising: (a) surgically creating access to the proliferating tissue in a patient; (b) surgically resecting at least a portion of the proliferating tissue to create a resection cavity within body tissue;
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(c) providing an interstitial brachytherapy apparatus for 36. An interstitial brachytherapy apparatus for delivering delivering radioactive emissions comprising: radioactive emissions to an internal body location compris(i) a catheter body member having a proximal end and ing: distal end; (a) a catheter body member having a proximal end and (ii) an inner spatial volume disposed proximate to the 5 distal end; distal end of the catheter body member; (b) an inner spatial volume disposed proximate to the (iii) an outer spatial volume defined by an expandable distal end of the catheter body member; surface element disposed proximate to the distal end (c) an outer spatial volume defined by an expandable of the body member in a surrounding relation to the surface element disposed proximate to the distal end of 10 inner spatial volume; and the body member in a surrounding relation to the inner (iv) a radiation source disposed in the inner spatial spatial volume; and volume; (d) a radiation source disposed in the inner spatial vol(d) intraoperatively placing the interstitial brachytherapy ume; apparatus into the resection cavity; wherein the inner and outer spatial volumes are configured (e) adapting the expandable surface element to contact 15 to provide a minimum prescribed absorbed dose for delivtissue surrounding the resection cavity to conform the ering therapeutic effects to a target tissue, the target tissue tissue to the desired shape of the expandable surface being defined between the outer spatial volume expandable element; surface and a minimum distance outward from the outer (f) delivering a prescribed absorbed dose to tissue sur- 20 spatial volume expandable surface, the apparatus providing rounding the apparatus; and a controlled dose at the outer spatial volume expandable (g) removing the interstitial brachytherapy apparatus. surface to reduce or prevent necrosis in healthy tissue 35. The method of claim 34, wherein the step of adapting proximate to the expandable surface. the expandable surface element includes expanding the outer surface volume. * * * * *
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EXHIBIT C
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