Ex Parte Mollison et alDownload PDFPatent Trial and Appeal BoardFeb 16, 201612041537 (P.T.A.B. Feb. 16, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/041,537 03/03/2008 45159 7590 02/18/2016 SQUIRE PB (Abbott) 275 BATTERY STREET, SUITE 2600 SAN FRANCISCO, CA 94111-3356 FIRST NAMED INVENTOR Karl W. Mollison 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. 089035.00337 1588 EXAMINER BERRIOS, JENNIFER A ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 02/18/2016 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): sfripdocket@squirepb.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte KARL W. MOLLISON, ANGELA M. LECAPTAIN, SANDRA E. BURKE, KEITH R. CROMACK, PETER J. TARCHA, YEN-CHIH J. CHEN, and JOHN L. TONER Appeal2013-008055 Application 12/041,5 3 7 Technology Center 1600 Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and ROBERT A. POLLOCK, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to a medical device comprising therapeutic substances. The Examiner has finally rejected the claims as obvious under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 134. The Examiner's rejections are affirmed. STATEMENT OF CASE The claims are directed to a medical device comprising a Formula I compound and an immunosuppressive agent. The Specification of the application at issue in this appeal ("Spec.") teaches that the Formula I Appeal2013-008055 Application 12/041,537 compound can be coated on a medical device, such as a stent, to reduce restenosis after coronary angioplasty. Spec. i-fi-f 13, 30. Appellants appeal from the Examiner's final rejection of claims 1, 7- 14, 17, and 18. The claims stand finally rejected by the Examiner as follows: 1. Claims 1 and 7-14 under 35 U.S.C. § 103(a) as obvious in view of Wright et al. (US Patent Application 2001/0027340 Al, published Oct. 4, 2001) (hereinafter "Wright"), Or et al. (US 5,527 ,907, issued June 18, 1996) (hereinafter "Or"), Morris et al. (US 5,646,160, issued July 8, 1997) (hereinafter "Morris"), Berg et al. (US 5,464,650, issued Nov. 7, 1995) (hereinafter "Berg"), and Hossainy et al. (US 6,153,252, issued Nov. 28, 2000) (hereinafter "Hossainy"). 2. Claims 1, 7-14, and 17 under 35 U.S.C. § 103(a) as obvious in view of Wright, Or, Morris, Berg, Hossainy, and Lewis et al. (Cross linkable coatings from phosphorylcholine-based polymers, 22 BIOMATERIALS 99-111 (2001 )) (hereinafter "Lewis"). 3. Claims 1, 7-14, and 18 under 35 U.S.C. § 103(a) as obvious in view of Wright, Or, Morris, Berg, Hossainy, and Gordon et al. (Mechanisms of Restenosis and Redilation Within Coronary Stents---Quantitative Angiographic Assessment, 21JACC1166-74 (1993)) (hereinafter "Gordon"). The only independent claim on appeal is claim 1. Claim 1 is reproduced below: 1. A medical device comprising a supporting structure capable of containing or supporting a pharmaceutically acceptable carrier or excipient, said carrier or excipient containing the therapeutic substance of Formula I 2 Appeal2013-008055 Application 12/041,537 or a pharmaceutically acceptable salt or prodrug thereof and at least one other therapeutic substance, wherein the other therapeutic agent is an imnmnosuppressant agent selected from the group consisting of azathioprine sodium, brequinar sodium, gusperimus trihydrochloride, mizoribine, Cyclosprin A, tacrolimus, leflunomide, glucocorticoids, orthoclone, and antithymyocyte globulins, wherein the amount of therapeutic agent of Formula I in the medical device is from about 1 microgram to about 120 microgram. REJECTION 1 Claim 1 is directed to a medical device comprising: 1) a therapeutic substance of Formula I; and 2) an immunosuppressant agent selected from a specific list of drugs. The Formula I compound is present in the medical device in an amount from about I microgram to about 120 micrograms. The Examiner found the cited publications suggested the claimed device. The Examiner's findings and reasoning follow. Formula I The Examiner found that Or describes methoxy-methylcarbamate rapamycin, which the Examiner found corresponds to the Formula I compound recited in the claim. Final Rej. 3. 3 Appeal2013-008055 Application 12/041,537 Or teaches that methoxy-methylcarbamate rapamycin is a derivative of rapamycin, and that an object of its invention is to identify derivatives which have the immunosuppressive activity of rapamycin, but not rapamycin's side effects. Or, col. 3, 11. 34--41; col. 4, 11. 45-54; Example 17 (col. 54, 11. 15--41 ). The Examiner also found that Or teaches that the Formula I compound, i.e., methoxy-methylcarbamate rapamycin, has immunosuppressive activity. Final Rej. 3. The Examiner found that Wright describes a medical device, such as a stent, coated with rapamycin but not with the Formula I compound and a second therapeutic agent. Id. Rapamycin is described in Wright as having anti-proliferative and anti-inflammatory activity, and like Or's compounds (Or, col. 91, 1. 25-26), is used by Wright to prevent restenosis. Wright i-fi-1 27, 28. The Examiner found it obvious to have utilized Or's methoxy- methylcarbamate rapamycin in place of Wright's rapamycin because Or's compound has immunosuppressive activity as does rapamycin. Final Rej. 3--4. Immunosuppressant agent The Examiner acknowledged that neither Wright nor Or teaches a device coated with with rapamycin or a rapamycin derivative in combination with a second immunosuppressant agent such as a glucocorticoid. Final Rej. 4. However, the Examiner found that Morris describes combining rapamycin with a second drug, mycophenolic acid, which is an anti- 4 Appeal2013-008055 Application 12/041,537 proliferative antimetabolite. Id. Morris teaches that both agents can be administered by a stent to treat restenosis. Id. The Examiner further found that Berg describes applying dexamethasone to a stent. Id. Dexamethasone is a glucocorticoid. Id. Glucocorticoids are specifically recited in claim 1 as the immunosuppressive agent. The Examiner determined that the skilled worker would have had reason to combine the Formula I compound of Or with dexamethasone of Berg since both are used for the treatment of restenosis and it would have been obvious to combine therapeutics used for the same purpose. Id. at 4--5. The Examiner found one of skill in the art would have had a reasonable expectation of success because Morris teaches that rapamycin coated stents can be effectively combined with anti-inflammatory/ anti-proliferative agents to treat restenosis. Id. at 5. Amount of Formula I compound Claim 1 requires the Formula I compound to be present in amount from about 1 microgram to about 120 micrograms. The Examiner found that Hossainy teaches a process for coating stents, and teaches coating a stent with amounts of rapamycin that fall within the claimed range. Final Rej. 5. Specifically, the Examiner found that Example 5 of Hossainy "demonstrates the use of rapamycin on a stent, wherein the rapamycin is used in a total amount of 80 micrograms (which falls within the 1-120 micrograms instantly claimed). Example 10 demonstrates 2 5 Appeal2013-008055 Application 12/041,537 rapamycin/stents formulated with 32 micrograms and 166 micrograms respectively." Id. Based on this teaching, the Examiner concluded it would have been obvious to have used such amounts for Or's compound. Id. Discussion Appellants challenge the Examiner's rejection. We address their arguments below. Was there a reason to have used methoxy-methylcarbamate rapamycin in Wright and Morris? Appellants contend that the cited publications fail to provide any suggestion or motivation to one of ordinary skill in the art to substitute Or's methoxy-methylcarbamate rapamycin1 for rapamycin in the medical device of Wright or Morris for inhibiting restenosis with a reasonable expectation of success. Appeal Br. 13. Specifically, Appellants argue that Or does not demonstrate that methoxy-methylcarbamate rapamycin has anti-proliferative activity toward smooth muscle cells (SMC) of blood vessels as does rapamycin as taught by Wright and Morris. Id. Appellants contend this lack of teaching is significant because 1) Wright teaches the rapamycin' s ability to inhibit SMC proliferation in animal models of restenosis is based on its combined activity in inhibiting both inflammation and proliferation (id.) and 2) Morris teaches that rapamycin's activity in preventing or treating 1 Appellant does not contest that Or specifically discloses methoxy- methylcarbamate rapamycin, which corresponds to the claimed Formula I compound. 6 Appeal2013-008055 Application 12/041,537 restenosis is based on its anti-proliferative activity, not its immune system activity (id. at 13-14). In other words, Appellants argue that the skilled worker would not have chosen Or's methoxy-methylcarbamate rapamycin because it had not been demonstrated to have anti-proliferative activity against smooth muscles cells in the artery, a critical activity when treating restenosis as taught by both Wright and Morris. In addition, Appellants contend that while Or demonstrates "the in vitro immunosuppressant activity of methoxy[-]methylcarbamate rapamycin ... [i]t does not demonstrate that methoxy-methylcarbamate rapamycin has antiproliferative activity toward smooth muscle cells (SMC) of blood vessels by any biological testing." Reply Br. 3. Or teaches that, "[ w ]hen examined for immunomodulatory activity using a common in vitro biological assay, the compounds of the invention are seen to be potent immunosuppressive agents." Or, col. 33, 11. 4---6. Or also teaches: "The compounds of this invention possess immunosuppressive, antimicrobial, antifungal, antiviral, antiinflammatory and antiproliferative activity." Id. at col. 33, 11. 7-9. In addition to this, Or teaches: The ability of the compounds of the invention to treat proliferative diseases can be demonstrated according to the methods described in Bunchman ET and CA Brookshire, Transplantation Proceed. 23 967-968 (1991); Yamagishi, et al., Biochem. Biophys. Res. Comm. 191 840-846 (1993); and Shichiri, et al., J. Clin. Invest. 87 1867-1871 (1991). Proliferative diseases include smooth muscle proliferation, systemic sclerosis, cirrhosis of the liver, adult respiratory distress syndrome, idiopathic cardiomyopathy, lupus erythematosus, diabetic retinopathy or other retinopathies, psoriasis, scleroderma, prostatic hyperplasia, cardiac 7 Appeal2013-008055 Application 12/041,537 hyperplasia, restenosis following arterial injury or other pathologic stenosis of blood vessels. Or, col. 91, 11. 14--26. Thus, Or discloses that the compounds of its invention, which would include methoxy-methylcarbamate rapamycin, have antiproliferative activity. While we agree with Appellants that Or did not test the compounds for antiproliferative activity or their ability to inhibit smooth muscle cell proliferation, the evidence of record establishes a reasonable expectation that its compound would possess such activity. Or discloses at column 33, lines 7-9, that the rapamycin derivatives, including methoxy-methylcarbamate rapamycin, would have both anti- inflammatory and antiproliferative activity, activities identified by Morris as important in treating restenosis. Thus, even if Or did not test the compounds for antiproliferative activity, Or asserted they would have it. Appellants have not provided evidence to doubt it. Or also specifically discloses that its compounds can be used to treat proliferative diseases, including restenosis (id. at col. 91, 11. 14--26), again indicating Or's belief that its rapamycin derivatives would possess antiproliferative activity, and that it would be routine to confirm so using the disclosed published methods (id.). Again, Appellants not provided arguments or evidence that would undermine Or's credible assertions. Even assuming that, absent actual testing, Or's statement that its rapamycin derivatives have antiproliferative activity is speculative, we are still of the opinion that this does not defeat the obviousness rejection. First, Or's statements are a clear suggestion to use its rapamycin derivatives to treat a proliferative disease, such as restenosis. Certainty, confirmed by biological testing, is not necessary to establish obviousness. 8 Appeal2013-008055 Application 12/041,537 '"Obviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success.' [In re O'Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988)]." In re Kubin, 561F.3d1351, 1360 (Fed. Cir. 2009). The statements by Or that its compounds possess antiproliferative activity provide evidence that the skilled worker reasonably expected that such compounds possess the stated activity. Appellants have not provided evidence to rebut this reasonable expectation or cast doubt on Or's assertions. Second, based on Or's explicit suggestion to use its rapamycin derivatives to treat restenosis, it would have been "obvious to try" to do so. To differentiate between proper and improper applications of "obvious to try," this court outlined two classes of situations where "obvious to try" is erroneously equated with obviousness under § 103. In the first class of cases, what would have been "obvious to try" would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result; where the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful. [In re O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)] In such circumstances, where a defendant merely throws metaphorical darts at a board filled with combinatorial prior art possibilities, courts should not succumb to hindsight claims of obviousness. The inverse of this proposition is succinctly encapsulated by the Supreme Court's statement in KSR that where a skilled artisan merely pursues "known options" from a "finite number of identified, predictable solutions," obviousness under§ 103 arises. [KSR Intern. Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).] The second class of 0 'Farrell's impermissible "obvious to try" situations occurs where 9 Appeal2013-008055 Application 12/041,537 what was "obvious to try" was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it. 853 F.2d 903. In re Kubin, 561 F.3d at 1359. In this case, there is no evidence that the skilled worker would have had to vary parameters and make numerous choices. Rather, Wright (at i-f 45) and Morris (at col. 3, 11. 47-51; col. 11, 11. 52-56) provide explicit guidance on how to use rapamycin on a medical device. There is also no evidence that Appellants are claiming a new technology. It remains unchallenged that the use of rapamycin on a stent to treat restenosis was known as established by each of Wright and Morris. Or's object was to synthesize new derivatives of rapamycin, which possessed rapamycin activity, but lacked its side effects. Or, col. 4, 11. 45-54. While Appellants argue that the precise mechanism of rapamycin action was still being investigated and unpredictable (Appeal Br. 14; Reply Br. 3--4), Wright, Morris, and Or agree that rapamycin possesses immunosuppressive (Or), anti-inflammatory (Wright, Or), and antiproliferative (Wright, Morris, Or) activities which were believed to useful in treating restenosis. Or specifically discloses scientific studies describing rapamycin' s activities. Or, col. 3, 11. 25-41. Wright also describes scientific studies of rapamycin's mechanism of action. Wright i-fi-127, 28. Wright's statement about the "precise mechanism of rapamycin is still under active investigation" was in the context of the mechanism by which it inhibited T-cell proliferation and displayed anti-inflammatory activity, not any doubt that it had possessed such activities. Id. at i-f 28. 10 Appeal2013-008055 Application 12/041,537 Was there a reason to combine Or's compound with dexamethasone? Appellants contend that Wright, Or, Morris, and Berg fail to provide any suggestion or motivation to one of ordinary skill in the art at the time the invention was made to combine Or's methoxy-methylcarbamate rapamycin with dexamethasone in a medical device for inhibiting restenosis. Appeal Br. 15. Appellants argue that the Examiner's reasoning that both rapamycin and dexamethasone are therapeutic equivalents and therefore obvious to have combined for the same purpose is flawed because there is no evidence in the record these agents were recognized as equivalents. Id. Appellants also argue that dexamethasone appears in a list of a large number of drugs without any reason to have selected it to combine with methoxy- methylcarbamate rapamycin. Id. Appellants' arguments do not persuade us that the Examiner erred. While the Examiner used the language "functionally equivalent" when formulating the rejection (Final Rej. 4--5), it was in the context of both being effective antiproliferative agents to treat restenosis (Answer 9). Morris combines rapamycin and mycophenolic acid, both antiproliferative agents, to treat restenosis. Morris, col. 3, 11. 47-52; col. 4, 11. 12-15; col. 8, 1. 49 to col. 10, 1. 46. Thus, the concept of providing two therapeutic antiproliferative agents to treat a hyperproliferative disease, such as restenosis, is taught by Morris. Since Berg teaches that dexamethasone was known to treat restenosis and inhibit proliferation associated with arterial injury (Berg, col. 7, 11. 4--15), it would have been obvious in view of Morris to have combined it with rapamycin, e.g., to replace Morris's mycophenolic acid with dexamethasone. 11 Appeal2013-008055 Application 12/041,537 Dexamethasone appears in a list in Berg, but there are also individual examples of it. Berg, col. 2, 11. 55---60 (in a list of drugs, including a list of glucocorticoids ), col. 3, 11. 14--22 and Examples 1-7 (specific examples of dexamethasone only). Even were dexamethasone to appear only in a long list of drugs, it would have still have been obvious to have chosen it because Berg teaches that every drug in the list is effective. See Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) ("That the '813 patent discloses a multitude of effective combinations does not render any particular formulation less obvious.) The specific examples using dexamethasone only reinforce the obviousness of selecting it, particularly the experimental evidence that "dexamethasone-coated stents reduced the amount of proliferation associated with the arterial injury." Berg, col. 7, 11. 14--15. Consequently, we do not find Appellants' arguments about the lack of reason to have selected dexamethasone to be supported by the weight of the evidence before us. Was it obvious to select the recited amounts of the Formula I agent? Appellants contend that one of ordinary skill in the art would not have been motivated to select the amount of 1 microgram to about 120 micrograms for methoxy-methylcarbamate rapamycin with a reasonable expectation of success. Appeal Br. 16. Appellants argue that Hossainy teaches a broad range of effective amounts, and the exemplification of 80 micrograms in Example 5 is not specifically for rapamycin. Id. Appellants' argument is not persuasive. The Examiner specifically relied on Example 10 in Hossainy where rapamycin was utilized on stents in amounts within the 12 Appeal2013-008055 Application 12/041,537 claimed range. Hossainy, Example 10. Final Rej. 5. Appellants have not identified a flaw in this finding. REJECTION 2 The Examiner further cited Lewis for specific limitations in claim 17. Final Rej. 6. Appellants do not identify an error in the rejection, but rather rely on the same unpersuasive arguments they did for claim 1. Appeal Br. 17. Because we do not find a flaw in the Examiner's finding and conclusions, we affirm the rejection for the reasons set forth by the Examiner. REJECTION 3 The Examiner further cited Lewis for specific limitations in claim 18. Final Rej. 6-7. Appellants do not identify an error in the rejection, but rather rely on the same unpersuasive arguments they did for claim 1. Appeal Br. 18. Because we do not find a flaw in the Examiner's finding and conclusions, we affirm the rejection for the reasons set forth by the Examiner. TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 13 Copy with citationCopy as parenthetical citation