Ex Parte Fernandes et al

Patent Trial and Appeal BoardJun 29, 2018

12062230 (P.T.A.B. Jun. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/062,230 04/03/2008 Brian Fernandes 28390 7590 07/03/2018 MEDTRONIC VASCULAR, INC. IP LEGAL DEPARTMENT 3576 UNOCAL PLACE SANTA ROSA, CA 95403 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 ATTORNEY DOCKET NO. CONFIRMATION NO. PA1679.0l/LG10158.L32 9913 EXAMINER SGAGIAS, MAGDALENE K ART UNIT PAPER NUMBER 1632 NOTIFICATION DATE DELIVERY MODE 07 /03/2018 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address( es): rs.vasciplegal@medtronic.com rs.patents.five@medtronic.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte BRIAN FERNANDES, JACK CHU, and PREMA GANESAN Appeal2017-008345 Application 12/062,230 1 Technology Center 1600 Before TONI R. SCHEINER, DEMETRA J. MILLS, and RICHARD M. LEBOVITZ, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to an ultrasonic diagnostic apparatus. The Examiner rejected the claims as obvious under 35 U.S.C. Â§ 103. Appellants appeal the rejections pursuant to 35 U.S.C. Â§ 134. We have jurisdiction under 35 U.S.C. Â§ 6(b ). The rejections are affirmed-in-part and reversed-in-part. A new ground of rejection is set forth pursuant to 37 C.F.R. Â§ 41.50(b). 1 The Appeal Brief ("Appeal Br.") 2 lists Medtronic, Inc. as the real-party- in-interest. Appeal2017-008345 Application 12/062,230 STATEMENT OF THE CASE Claims 31-33, 39-47, and 50-57 stand rejected in the Answer by the Examiner as follows: 1. Claims 31, 32, 39, 41--43, 45--47, 51, 56, and 57 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond (Stroke, 1999, 30: 1657-1664), Zuk 2001 (Tissue Eng., 2001, 7:211-228), Wagner (Experimental Hematology, 2005, 33:1402-16), Kehat (J. Clin. Invest., 2001, 108:407--414), Hedrick (WO 03/022988 A2; published March 20, 2003), Leonhardt (U.S. Pat. No. 5,713,917, published February 3, 1998), and Moein (U.S. Pat. No. 6,547,767 Bl, issued April 15, 2003). Ans. 2-3. 2. Claims 31 and 33 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and Liechty (Nature Medicine, 2000, 6:1282-1286). Ans. 15. 3. Claims 31 and 33 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk, Wagner, Kehat, Hedrick, Leonhardt, Moein, Zuk 2002 (Molecular Biology of the Cell, 2002, 13:4279-4295), and Baum (Proc. Natl. Acad. Sci., 1992, 89:2804--2808). Ans. 17. 4. Claims 31 and 39-44 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and Cragg (U.S. Pub. Pat. App. No. 2002/0016611 Al, published Feb. 7, 2002). Ans. 19. 5. Claims 31 and 50 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and Simper (Circulation, 2002, 106: 1199-1204). Ans. 21. 6. Claims 31 and 52 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, and 2 Appeal2017-008345 Application 12/062,230 Wobus (Embryonic Stem Cells: Methods in Molecular Biology, 2001, 185:127-156). Ans. 23. 7. Claims 31 and 52-54 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, Wobus, and Drab (FASEB J, 1997, 11:905-915). Ans. 24. 8. Claims 31 and 55 under 35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Zuk 2001, Wagner, Kehat, Hedrick, Leonhardt, Moein, W obus, Simper, and Dennis (Stem Cells, 2002, 20:205-214). Ans. 25-26. In the Examiner's Answer, the Examiner withdrew the rejections in the Final Action, and set forth the new grounds of rejection listed above. Leonhardt and Moein are newly cited in all the rejections. However, only the basis of Rejection 1 changed to reflect the new teachings in Leonhardt and Moein. The bases of rejections 2-8, involving the dependent claims only, did not change. Rejections 2-8 were modified to include the newly cited Leonhardt and Moein; however, the latter publications were not relied upon in finding the limitations appearing in the dependent claims obvious. There are two independent claims, claims 31 and 51. Claim 31, which is representative, is reproduced below: 31. A method of treating an aortic aneurysm in an individual at the aortic aneurysmal site using self-derived cells, comprising: -harvesting adult stem cell-containing tissue from the individual wherein said tissue is selected from the group consisting of adipose tissue, bone marrow and peripheral blood; -isolating adult mesenchymal stem cells from the tissue; -culturing the isolated adult mesenchymal stem cells under conditions where the stem cells form spontaneously contracting vascular smooth muscle cells, wherein the spontaneously contracting vascular smooth muscle cells express the vascular-specific splice variant of the vascular smooth muscle myosin heavy chain (MHC); and 3 Appeal2017-008345 Application 12/062,230 -delivering the cells, after culturing, directly into the wall of a blood vessel at said aortic aneurysmal site by liquid delivery means wherein said blood vessel wall is repaired and said aneurysm is treated in said individual. REJECTION 1 Claim 31 is directed to a method of treating an aortic aneurysm in an individual using "self-derived cells." The method recites the steps of isolating mesenchymal stem cells from a tissue and delivering them into the wall of a blood vessel. The cells are obtained from a tissue of the individual containing adult stem cells. The tissue is adipose tissue, bone marrow, or peripheral blood. The cells are cultured under conditions where the stem cells form spontaneously contracting vascular smooth muscle cells, wherein the spontaneously contracting vascular smooth muscle cells [VSMC] express the vascular-specific splice variant of the vascular smooth muscle myosin heavy chain (MHC). Claim 51 has substantially the same limitations. The Examiner found that Raymond describes treating a carotid artery aneurysm in a dog at the aneurysmal site using vascular smooth muscle cells ("VSMC") harvested from an artery tissue of the dog. Ans. 3--4. The Examiner further found that Raymond describes "delivering the vascular smooth muscle cells directly into the lateral wall aneurysm of carotid artery to completely occlude/embolize said aneurysm." Id. at 4. The Examiner acknowledged that Raymond does not describe isolating mesenchymal cells from adipose tissue as one of the three possible sources of cells recited in claim 31. Ans. 5. However, the Examiner cited several prior art publications that the Examiner found to describe obtaining 4 Appeal2017-008345 Application 12/062,230 vascular smooth muscle cells from stem cells. These findings are summarized below: 1) The Examiner found that Zuk 2001 teaches isolating stem cells from adipose tissue (processed lipoaspirate or PLA) and that, after culturing the cells, these cells express skeletal muscle myosin heavy chain (MHC). which is a well-known marker indicative of initiation of differentiation toward vascular smooth muscle cells (VSMCs) (cultured under conditions where the stem cells form VSMCs) (see page 222, Fig. 7). Zuk [2001] isolated PLA cells that comprise MSCs that express skeletal muscle MHC are structurally identical as instantly claimed cells .... Ans. 5 (boldface omitted). 2) The Examiner further cited Kehat for teaching culture conditions for embryonic stem cells that result in muscle cells that spontaneously contract. Ans. 6. 3) The Examiner also cited Galmiche2 as teaching that bone marrow mesenchymal cells differentiate in culture into vascular smooth muscle-like cells. Ans. 6. 4) The Examiner found that Hedrick teaches mesenchymal stem cells present in lipoaspirate that "possess the capacity, for myogenic differentiation showing the expression of the MHC, a later marker of myogenic differentiation." Ans. 6. The Examiner newly cited Leonhardt and Moein for teaching delivery of cells into the blood vessel wall. Ans. 7. 2 Galmiche, Blood, 1993, 82(1):66-76. Galmiche was cited by the Examiner for the first time in the Answer, but was not included in the statement of the rejection. 5 Appeal2017-008345 Application 12/062,230 The Examiner concluded that one of ordinary skill in the art would have had reason: to substitute the Raymond VSMCs directly delivered into the lateral wall aneurysm of carotid artery for treating the aneurysmal site with the Zuk/Kehat VSMCs derived from PLA MSCs differentiated into VSMCs given both Raymond and Zuk/Kehat and Hedricks teach VSMCs and autologous nature of stem cells, VSMCs derived from PLA MSCs together with their multipotentiality and ease of procurement, make these cultured MSCs an excellent choice for many tissue engineering strategies and cell-based therapies. Ans. 8. The Examiner also found that Leonhardt and Moein provide the motivation for direct delivery of cell-based therapeutic agent into the aneurysmal site because these publications teach the benefit of delivering therapeutic agents with a catheter into a blood vessel wall, including delivering therapeutic cells into the tunica media of the blood vessel wall. Id. Discussion Would it have been obvious to have produced the contracting vascular smooth muscle cells as claimed? Appellants contend that the Examiner did not identify a reason to have "cultur[ ed] the isolated adult mesenchymal stem cells under conditions where the stem cells form spontaneously contracting vascular smooth muscle cells" as required by independent claims 31 and 51. Reply Br. 2-3. While Appellants acknowledge that Kehat teaches embryoid bodies, as does the '230 Specification, Appellants distinguish Kehat based on its teaching that the embryoid bodies form cardiomyocytes, which are not vascular smooth muscle cells. Appellants identify disclosure in the '230 6 Appeal2017-008345 Application 12/062,230 Specification that "the presence of selected cytokines, growth factors, and angiogenic factors can affect the cells into which stem cells differentiate" as evidence that the conditions in Kehat resulted in a different cell type than the cell type which is claimed. Id. at 3. We agree with Appellants that the Examiner erred in finding that Kehat describes vascular smooth muscle cells. Kehat expressly discloses forming cardiomyocytes from embryoid bodies. Kehat, Abstract. The Examiner did not establish that cardiomyocytes are vascular smooth muscle cells. It is unclear why Appellants did not address the additionally cited Zuk 2001 and Hedrick publications. However, we have looked at these publications and find each disclose the expression of MyoD 1 in cells, which is indicative of skeletal muscle, not vascular smooth muscle cells. Zuk 2001 222 (Fig. 7); Hedrick 61; Weintraub. 3 Thus, neither Kehat, Zuk 2001, nor Hedrick describes vascular smooth muscle cells as required by the claims. Nonetheless, Galmiche teaches that stromal cells obtained from bone marrow cells, when placed into culture, differentiate into vascular smooth muscle cells. Galmiche 66 (Abstract). Stromal cells contain mesenchymal stem cells. Zuk 2001 212 ("The bone marrow stromal, in both animals and humans, is heterogenous [heterogeneous] in composition, containing several cell populations, including a stem cell population termed mesenchymal stem cells or MSCs."). 3 Weintraub, Science, 1991, 251(4995):61---66 (Abstract only). 7 Appeal2017-008345 Application 12/062,230 While Gahniche does not teach the conditions to obtain spontaneously contracting vascular smooth cells, Drab, cited in Rejection 7, discloses such conditions, including the addition of retinoic acid, which is the same compound utilized in the '230 Specification to induce vascular smooth muscle differentiation. Drab 906 ("Cell cultures"), 908 ("RESULTS"; Fig. 1); '230 Spec. ,-r 47. Kehat teaches spontaneously contracting muscles cells and the advantage of implanting such cells derived from stem cells into damaged tissue. Kehat 407, 414. Thus, it would have been obvious to one of ordinary skill in the art to have utilized the cells in Galmiche, differentiated as described in Drab, as the source of cells for Raymond's aneurysm repair method. With respect to the limitation in the claims that the source of cells is peripheral blood, the '230 Specification admits that it was known to isolate smooth muscle cells from it. '230 Spec. i-f 41. The publication cited in the '230 Specification for this teaching is Simper, which teaches that the expansion of smooth muscle cell progenitor cells "may have implications for cell, gene, and tissue engineering approaches to vascular disease" (Simper 1203-1204), providing reason to have used them in Raymond's method. 8 Appeal2017-008345 Application 12/062,230 Although Gahniche was cited in the Answer, it was not a part of the statement of the rejection of record. Consequently, we shall designate this rejection as new grounds under 37 C.F.R. Â§ 41.50(b). 4 In addition, we newly cite admissions in the Specification and Simper. Delivery cells into the wall of a blood vessel The Examiner newly cited Leonhardt and Moein to meet the limitations of delivering the cells into the wall of a blood vessel, or into the tunica media wall of a blood vessel, at an aortic aneurysm cite as recited in claims 31 and 51, respectively. Appellants contend that the Examiner did not provide a rational basis to have used Leonhardt and Moein to deliver vascular smooth muscle cells to the wall of a blood vessel to treat an aneurysm. Reply Br. 4. Appellants contend: 4 [T]he Examiner identified no teaching in Moein to treat an aortic aneurysmal site or to deliver a cell at an aortic aneurysmal site. We therefore view the reference to Raviola and Mitsui, at page 4 of the Answer [but not in the statement of the rejection], as an improper effort to bring these references in the "back door". Compare In re Hoch, 428 F.2d 1341, 1342 n. 3, 166 USPQ 406, 407 n. 3 (CCPA 1970) (where reference is relied on to support a rejection, whether or not in a "minor capacity", there would appear to be no excuse for not positively including that reference in statement of the rejection). Ra viola and Mitsui are not positively included in the statement of rejection, and we have considered the issue under 3 5 USC 103 based solely on the evidence contained in Ishikawa and Billmeyer. Ex parte Raske, 28 USPQ2d 1304, 1305 (BPAI 1993). 9 Appeal2017-008345 Application 12/062,230 Leonhardt does not teach "treating aortic aneurysm as claimed," as asserted by the Examiner. (Examiner's Answer, page 15.) ... [N]othing in Leonhardt teaches using "self- deri ved cells" or delivering cells directly into the wall of a blood vessel. Reply Br. 5. We agree that Leonhardt does not describe administering cells into the wall of a blood vessel. However, as found by the Examiner, Moein teaches this step: A first syringe assembly is supported by the catheter assembly for allowing a first therapeutic substance to be injected into a tissue of a passageway .... The needle of the first syringe assembly can be configured to penetrate into the tunica media layer of a blood vessel wall for administering the first therapeutic substance to a region of the tunica media layer of the blood vessel wall. Moein, col. 3, 11. 26-41. Moein teaches that the therapeutic substance can include genetically engineered cells. Moein, col. 9, 1. 66 to col. 10, 1. 1. As discussed in Raymond, it is not likely that the grafted vascular cells became part of the neointima of the vessel wall, but rather it is more likely that the vascular cells participate in the healing process by producing extracellular matrix (ECM) materials. Raymond 1662 ("VSMC Grafts and Vessel Wall Healing"), 1657 (first paragraph). Moein teaches delivering therapeutic substances into the blood vessel wall, where such substances include cells. Moein, col. 9, 1. 66 to col. 10, 1. 1. Thus, it would have been obvious to one of ordinary skill in the art to have utilized Moein's technique to deliver cells into the wall of an aneurysm site to facilitate introduction of the cells into the wall of the blood vessel for delivery of therapeutic ECM to the damaged aneurysm site. 10 Appeal2017-008345 Application 12/062,230 We reverse Rejection 1, but set forth a new ground of rejection pursuant to 37 C.F.R. Â§ 41.50(b) as follows: Claims 31and51under35 U.S.C. Â§ 103(a) as obvious in view of Raymond, Galmiche, Drab, Moein, Zuk 2001, Kehat, Simper, and Admissions in the '230 Specification. The teachings in Simper and the Admissions are cited to reach the "peripheral blood" limitations of the claims. We leave it to the Examiner to address the obviousness of dependent claims 32, 39, 41--43, 46, 47, 56, and 57. REJECTIONS 2-8 Appellants did not provide arguments for rejections 2-8. We thus affirm these rejections for the reasons set forth by the Examiner. TIME PERIOD FOR RESPONSE This decision contains a new ground of rejection pursuant to 37 C.F.R. Â§ 41.50(b). Section 41.50(b) provides "[a] new ground of rejection pursuant to this paragraph shall not be considered final for judicial review." Section 41.50(b) also provides: When the Board enters such a non-final decision, the appellant, within two months from the date of the decision, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: ( 1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new Evidence relating to the claims so rejected, or both, and have the matter reconsidered by the examiner, in which event the prosecution will be remanded to the examiner. The new ground of rejection is 11 Appeal2017-008345 Application 12/062,230 binding upon the examiner unless an amendment or new Evidence not previously of Record is made which, in the opinion of the examiner, overcomes the new ground of rejection designated in the decision. Should the examiner reject the claims, appellant may again appeal to the Board pursuant to this subpart. (2) Request rehearing. Request that the proceeding be reheard under Â§41.52 by the Board upon the same Record. The request for rehearing must address any new ground of rejection and state with particularity the points believed to have been misapprehended or overlooked in entering the new ground of rejection and also state all other grounds upon which rehearing is sought. Further guidance on responding to a new ground of rejection can be found in the MPEP Â§ 1214.01. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a)(l). See 37 C.F.R. Â§Â§ 41.50(Â±), 41.52(b). AFFIRMED-IN-PART; REVERSED-IN-PART; 37 C.F.R. Â§ 41.50(b) 12