Ex Parte Zhang et alDownload PDFPatent Trial and Appeal BoardOct 5, 201712614901 (P.T.A.B. Oct. 5, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 9865-92IP 9486 EXAMINER MARVICH, MARIA ART UNIT PAPER NUMBER 1633 MAIL DATE DELIVERY MODE 12/614,901 11/09/2009 20792 7590 MYERS BIGEL, P.A. PO BOX 37428 RALEIGH, NC 27627 10/05/2017 Yuanyuan Zhang 10/05/2017 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte YUANYUAN ZHANG and ANTHONY AT ALA1 Appeal 2017-002085 Application 12/614,901 Technology Center 1600 Before JEFFREY N. FREDMAN, JOHN G. NEW, and JOHN E. SCHNEIDER, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method for treating incontinence using stem cells which have been rejected as not enabled. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE The Specification describes a method for producing a culture of stem cells derived from urine. Spec. 1. The stem cells can be used to treat a 1 Appellants identify the Real Party in Interest as Wake Forest University Health Sciences. Appeal Br. 2. Appeal 2017-002085 Application 12/614,901 variety of disorders including urinary incontinence (“UI”) and vesicoureteral reflux (“VCR”). Spec. 3. Claims 32—35, 37—43, and 45—56 are on appeal. Claims 32, 40, and 50 are the sole independent claims and read as follow: 32. A method of treating urinary incontinence (UI) or vesicoureteral reflux (VUR) in a mammalian subject in need thereof, comprising: administering urine stem cells to said subject in a treatment effective amount, wherein said cells are allogeneic or syngeneic with respect to said subject, and wherein said cells are provided in a pharmaceutically acceptable carrier. 40. A method of treating urinary incontinence (UI) or vesicoureteral reflux (VUR) in a mammalian subject in need thereof, comprising: administering urine stem cells to said subject in a treatment effective amount, wherein said cells are allogeneic or syngeneic with respect to said subject, wherein said administering is carried out by endoscopic administration, and wherein said cells are provided in a pharmaceutically acceptable carrier. 50. A method of treating urinary incontinence (UI) or vesicoureteral reflux (VUR) in a human subject in need thereof, comprising: administering urine stem cells to said subject in a treatment effective amount, wherein said cells are syngeneic with respect to said subject, and wherein said cells are provided in a pharmaceutically acceptable carrier, wherein said administering is carried out by endoscopic injection. 2 Appeal 2017-002085 Application 12/614,901 The claims have been rejected under 35U.S.C. § 112, first paragraph for failing to meet the enablement requirement. DISCUSSION Issue The issue is whether a preponderance of evidence supports the Examiner’s position that the claims are not enabled as required by 35 U.S.C. § 112, first paragraph. The Examiner finds that the Specification does not enable one skilled in the art to make or use the invention commensurate with the scope of the claims. Final Act. 5. The Examiner finds that the amount of direction provided by the Specification is narrow relative to the scope of the claims. Final Act. 6. The Examiner also finds that the art is unpredictable. Id. The Examiner finds that the claims are drawn to treating UI and VCR broadly and that there is no guidance as to how to proceed with the claimed course of treatment. Id. at 8. Appellants contend that the claims narrow in that they are directed to treating two specific disorders, UI and VCR. Appeal Br. 5. Appellants contend that the use of stem cells to treat UI and VCR was well known at the time of filing and produced predictable results. Appeal Br. 5—6. Appellants argue that the use of stem cells to treat UI and VCR was known in the art and that one skilled in the art would know how to use urine derived stem cells (“USC”) to treat UI and VCR. Appeal Br. 7. Appellants also argue that undue experimentation is not required to practice the invention. 3 Appeal 2017-002085 Application 12/614,901 Findings of Fact We adopt as our own the Examiner’s findings and analysis. The following findings are included for emphasis and reference convenience. FF1. The present Specification teaches that In some embodiments, USC and/or differentiated USC may be used in the treatment of urinary incontinence. For example, USC and/or USC differentiated into a skeletal myogenic lineage may be used in treatment of urinary stress incontinence in men in which there is urethral sphinctic dysfunction. USC and/or USC differentiated into a smooth muscle cell lineage may be used in treatment of urinary stress incontinence in women in which there is pelvic floor muscle dysfunction. In some embodiments, USC and/or differentiated USC may be used in the treatment of vesicoureteral reflux, in which there is a smooth muscle tissue defect at the ureteral orifice. Spec. 17. FF2. The Specification goes on to teach that In further embodiments, formulations of the invention include those for parenteral administration (e.g., subcutaneous, intramuscular, intradermal, intravenous, intraarterial, intraperitoneal injection) or implantation. In some embodiments, administration is carried out intravascularly, either by simple injection, or by injection through a catheter positioned in a suitable blood vessel, such as a renal artery. In another embodiment, administration is carried out as a graft to an organ or tissue to be augmented, as discussed above. Spec. 21. 4 Appeal 2017-002085 Application 12/614,901 FF3. The Zhang Declaration2 discloses the use of intraperitoneal delivery of USC to treat UI in rats. Zhang Decl. 112. FF4. Gras3 teaches that Independent of type and form of the donor tissue, it is still unclear how and where to inject the transplanted cells or tissue fragments. Given the complexity of the continence mechanism and the multifactorial pathophysiology of SUI, subtypes of patients responding differently to a particular type of treatment may also exist. Future studies need to define such subtypes, and to address in more detail whether injections should be trans-urethral or peri-urethral, whether the transplants should be delivered into the external sphincter, the internal sphincter or the submucosa, and whether ultrasound or EMG could be used for locating the correct position. Gras 821. Principles of Law “Section 112 requires that the patent specification enable those skilled in the art to make and use the full scope of the claimed invention without undue experimentation .... [S]ee also In re Goodman, 11 F.3d 1046, 1050 (Fed. Cir. 1993) (‘[T]he specification must teach those of skill in the art how to make and how to use the invention as broadly as it is claimed.’).” Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070—71 (Fed. Cir. 2005) (internal quotes omitted). 2 Declaration of Yuanyuan Zhang, M.D., Ph.D. under 37 C.F.R. § 1.132, filed Jan. 21, 2015 (“Zhang Decl”). 3 Gras and Lose, The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence, 90 Acta Obst. Et Glyn. Scand. 815— 824 (2011) (“Gras”). 5 Appeal 2017-002085 Application 12/614,901 Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the Specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. Factors to be considered in determining whether a disclosure would require undue experimentation . . . include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Information needed to satisfy 35 U.S.C. § 112, first paragraph, must be disclosed in the Specification, not in a later-filed declaration. “§ 112 requires that, unless the information is well known in the art, the application itself must contain this information; it is not sufficient to provide it only through an expert’s declaration.” In re Buchner, 929 F.2d 660, 661 (Fed. Cir. 1991). [Although] a specification need not disclose what is well known in the art. . ., that general, oft-repeated statement is merely a rule of supplementation, not a substitute for a basic enabling disclosure. . . . [W]hen there is no disclosure of any specific starting material or of any of the conditions under which a process can be carried out, undue experimentation is required; there is a failure to meet the enablement requirement that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art. It is the specification, not the knowledge of one skilled in the art, that must supply the 6 Appeal 2017-002085 Application 12/614,901 novel aspects of an invention in order to constitute adequate enablement. Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997). Analysis We find claim 32 to be representative of the rejected claims. Claim 32 is directed to a method for treating UI or VCR by administering allogenic or syngeneic urine stem cells. We agree with the Examiner that the Specification does not provide an enabling disclosure for the full breadth of the claims. Appellants and the Examiner have focused their arguments on four of the Wands factors, the breath of the claims, the state of the art and unpredictability of the art, the amount of guidance presented, and the presence of working examples. We address each of these factors below. Breath of the claims The Examiner finds that the scope of the claims is broad in that they address treating UI and VCR regardless of the underlying cause by any means of administration. Ans. 3. The Examiner finds that while UI and VCR are similar disorders, they have different means of treatment. Final Act. 9-10. Appellants contend that the claims are relatively narrow in that they are limited to treating UI and VCR and that one skilled in the art would expect that cell based therapy would work for both disorders. Appeal Br. 5. We find that the Examiner has the better position. Claim 32 is directed to treating UI or VCR whatever the cause by administering USC by any one of a variety or means. As Gras notes: “Given the complexity of the 7 Appeal 2017-002085 Application 12/614,901 continence mechanism and the multifactorial pathophysiology of SUI, subtypes of patients responding differently to a particular type of treatment may also exist” (FF 4). Even the Specification recognizes that urinary incontinence encompasses “urethral sphinctic dysfunction” in men and “pelvic floor muscle dysfunction” in women (Spec. 17:29-32). Zhang teaches: “Impairment of sphincter muscles or their neural and vascular support leads to stress urinary incontinence.” Zhang 13. Thus, Zhang demonstrates that urinary incontinence is not limited to muscle dysfunction, but may also be due to neural or vascular injuries. State of the Art and Unpredictability of the Art The Examiner finds that the art relating to the use of cell therapy to treat UI and VCR is immature and unpredictable. Ans. 3—5. The Examiner points to several articles published after the filing of the present application which teach that the use of cell therapy for treating UI and VCR was deemed to be immature and only of potential interest. Id. Appellants argue that the art is predictable in that the use of stem cells to treat UI and VCR was well known at the time of the invention. Appeal Br. 5; Reply Br. 3. Appellants argue that the references cited by the Examiner and the Declaration of Dr. Zhang support the conclusion that the art is predictable. Id. We again agree with the Examiner that the art at the time of the invention was immature and unpredictable. As the Examiner points out, physiological arts, which include stem cell therapy, is recognized as an unpredictable art. Ans. 3. The articles cited by the Examiner support this conclusion. Gras teaches the “pathophysiology underlying female SUI is 8 Appeal 2017-002085 Application 12/614,901 only partly understood” and the “female urinary continence mechanism is complex, with distinct anatomical components that are all potential targets for cell-based therapy.” Gras 817. Gras also states that “[independent of type and form of the donor tissue, it is still unclear how or where to inject the transplanted cells or tissue fragments.” Gras 821. Similarly, Becker states “Several populations of adult stem cells and progenitor cells have been studied as useful cellular sources in the treatment and reconstruction of urological organs. However, considerable basic research still needs to be performed to ensure the controlled differentiation and long-term fate of stem cells following transplantion.” Becker 1217 (emphasis added). Lin notes “SUI [stress urinary incontinence] animal models that have been utilized in published SC-for-SUI studies lack a critical clinical component, namely, the chronic nature of SUI.” Lin 840. Lin explains “Specifically, while most SUI patients incurred parturition-related urethral injuries years or decades ago, SUI animal models usually regain urinary continence within weeks.” Id. Lin also acknowledges: “One of the most pressing issues in SC research the lack of a clear understanding of how SCs exert their therapeutic effects.” Id. These uncertainties, coupled with the Specification’s lack of disclosure discussed below, leads to the conclusion that the art is immature and unpredictable. We have considered the Declaration of Dr. Zhang and find it unpersuasive. While Dr. Zhang points out that there have been studies using USC to treat UI, Dr. Zhang notes that the art considers it a “promising therapy.” Zhang Decl. | 8. Dr. Zhang goes on to point out that the 9 Appeal 2017-002085 Application 12/614,901 successful trials have used cells other than USC and that it is his opinion that USC will also be successful. Zhang Decl. Tflf 8 and 9. Dr. Zhang does not, however, explain the basis for his opinion that one skilled in the art would conclude that USC can be successfully used to treat UI. Amount of Guidance and Working Examples The Examiner finds that the Specification is devoid of any specifics as to how to use the USC to treat either UI or VCR. Final Act. 9—12. The Examiner finds that the one working example does not provide any guidance as to how the USC are to be administered. Ans. 6—7. Appellants contend that Example 12 provides sufficient guidance to one skilled in the art to use USC to treat UI or VCR. Appeal Br. 6. Appellants point to the Declaration of Dr. Zhang as demonstrating that USC can be successfully used to treat UI. Appeal Br. 6—7. Appellants contend that the use of cell based therapy to treat UI was well known in the art and that there is no need to teach that which is known in the art. Appeal Br. 7. The Examiner has the better position. The Specification lists several different means for expanding USC and administering USC but provides no specific guidance as to how to use the techniques to administer USC in a manner that will treat UI or VCR. FF2. While Example 12 does disclose administering USC via subcutaneous injection, Spec. 36, the Example only shows that the injected cells form capillaries and can differentiate into muscle cells. Id. at 37. The Example does not demonstrate successful treatment of UI or VCR. As noted above, even after the development of the invention, the art taught that there was need for guidance as to where and how to inject stem 10 Appeal 2017-002085 Application 12/614,901 cells to treat UI. FF4. Thus, Appellants reliance on the art to supplement the teachings of the Specification is misplaced. We have considered the Declaration of Dr. Zhang in this respect and find it unpersuasive. To begin, it is well established that enablement must be shown in the Specification and cannot be supplied by a later filed declaration. In re Buchner, 929 F.2d at 661. Thus, the declaration of Dr. Zhang cannot make up for the absence of an enabling disclosure. While Dr. Zhang discloses the use of USC to treat UI, Dr. Zhang does not relate the method he used to administer the cells to any teachings in the Specification or guidance available in the art. See Zhang Deck ]Hf 12—14. Thus, the Declaration does not demonstrate that one skilled in the art, using the teachings of the Specification and the knowledge of the art, would have been able to successfully treat UI using USC at the time the application was filed in human patients where “most SUI patients incurred parturition-related urethral injuries years or decades ago,” rather than the rat model tested by Zhang because “SUI animal models usually regain urinary continence within weeks.” Lin 840. Because the claims encompass any mammalian species, whether human or “pig, goat, horse, mouse, rat, monkey, baboon, etc.” (Spec. 6:10-11), Dr. Zhang has not addressed issues regarding the full scope of the claimed invention. In addition, as discussed above, claim 32 is directed to the administration of USC by any means, not just intraperitoneal delivery used by Dr. Zhang. Compare claim 32 above with Zhang Deck 112. Thus, even if the Declaration demonstrated enablement, it would not be commensurate with the scope of the claims. 11 Appeal 2017-002085 Application 12/614,901 On balance, we conclude that the factors discussed above weigh in favor of the Examiner’s conclusion that claim 31 is not enabled. Claims 50—56 Appellants separately argue that claims 50-55 are enabled as they are directed to treating UI or VCR in a human where the US C are syngeneic and the USC are administered using endoscopic injection. Appeal Br. 8. With respect to claim 53, Appellants argue that the claim is enabled as it is directed to stress UI using endoscopic injection. Appeal Br. 9. Finally, Appellants argue that claim 56 is enabled as the claim is directed to intramuscular injection of the USC. Id. We have considered Appellants’ arguments and find them unpersuasive. As the Examiner points out, the Specification does not provide any guidance as to how to carry out the various means of administration recited in the claims. Ans. 8. For example, the Specification is devoid of any teaching as to where the USC should be administered. As Gras points out, this is a significant issue which needs to be addressed for stem cell treatment to be successful. FF4. Conclusion of Law We conclude that a preponderance of the evidence support the Examiner’s conclusion that claims 32 and 50-56 are not enabled as required by35U.S.C. § 112, first paragraph. Claims 33—35, 37—43, and 45 49 have not been argued separately and therefore fall with claim 32. 37 C.F.R. § 41.37(c)(l)(iv). 12 Appeal 2017-002085 Application 12/614,901 SUMMARY We affirm the rejection under 35U.S.C. § 112, first paragraph. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 13 Copy with citationCopy as parenthetical citation