Ex Parte WangDownload PDFPatent Trial and Appeal BoardJan 18, 201810655861 (P.T.A.B. Jan. 18, 2018) 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. 10/655,861 09/05/2003 Yi Wang AXJ-102RCE3 7250 133485 7590 01/22/2018 Nelson Mullins Riley & Scarborough LLP/Alexion One Post Office Square 30 th Floor Boston, MA 02109-2127 EXAMINER GAMBEL, PHILLIP ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 01/22/2018 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): ipboston.docketing@nelsonmullins.com chris. schlauch @nelsonmullins.com ipqualityassuranceboston@nelsonmullins.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte YI WANG 1 Appeal 2016-000567 Application 10/655,861 Technology Center 1600 Before JOHN G. NEW, RICHARD J. SMITH, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. § 134(a) involving claims directed to a method of treating asthma. Claims 1—11, 15—18, 21, 45— 50, 59, and 60 are on appeal as rejected under 35 U.S.C. § 103(a) and for obviousness-type double patenting.2 We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellant identifies the Real Party in Interest as “Alexion Pharmaceuticals, Inc.” Br. 2. 2 Although Appellant has not so stated in the briefing here, we note that this application and Appeal are related to U.S. Pat. App. Ser. No. 11/127,438 on appeal before the Board as Appeal No. 2017-003979. Appeal 2016-000567 Application 10/655,861 STATEMENT OF THE CASE The Specification states, “[ajsthma, bronchitis and emphysema are known collectively as Chronic Obstructive Pulmonary Diseases.” Spec. 1:14—15. The Specification further states, “[i]t is believed that when the asthmatic, human or animal, inhales an allergenic substance, sensitized IgE antibodies trigger mast cell degranulation in the lung interstitium. The mast cell degranulation releases histamine, bradykinin, and slow-reacting substance of anaphylaxis (SRS-A).” Id. at 2:5—9. The Specification further describes that a study by Lukacs et al. (Am. J. Physiol Lung Cell Mol. Physiol (2001)) reported that therapy using anti-C5a antibodies was effective to prevent an allergic asthmatic response in animals, but that the study did not provide a basis for extrapolating its results to using C5 inhibitors for asthma therapy. Id. at 4:3—5:10. The Specification further states, “[a]nti-C5 antibodies that have the desirable ability to block the generation of C5a have been known in the art since at least 1982.” Id. at 14:13—15. Claims 1—9 and 21 are independent claims. We conclude claim 1 is representative and it is reproduced below: 1. A method of treating asthma in a subject comprising administering an anti-C5 antibody to a subject susceptible to or having asthma, wherein the anti-C5 antibody inhibits the conversion of complement component C5 into C5a and C5b. Br. 15 (Claims App’x). 2 Appeal 2016-000567 Application 10/655,861 The following rejections are on appeal: Claims 1—11, 15—18, 21, 45—50, and 59-60 stand rejected under 35 U.S.C. § 103(a) over Fung 107,3 Fung 468,4 Evans,5 Lobb,6 Li,7 Konteatis,8 Magee,9 Lahn,10 and admitted prior art (see Spec. 6:8—18). Final Action 10. Claims 1—11, 15—18, 21, 45—50, and 59-60 stand provisionally rejected under the judicially created doctrine of obviousness-type double patenting over claims 31—32, 34, 38—39, 41—43, and 48 of copending application 11/127,438. Id. at 13. FINDINGS OF FACT We adopt the Examiner’s findings of fact, reasoning on scope and content of the claims and prior art, and conclusions set out in the Final Office Action and Examiner’s Answer. See Final Action 2—13; Answer 3— 18. The findings of fact set forth below are provided to highlight certain evidence. FF1. Evans is directed to and discloses, “[t]he use of anti-C5 antibodies, e.g., monoclonal antibodies, to treat glomerulonephritis . . . and other inflammatory conditions involving pathologic activation of the complement system''’ and, further, “compositions comprising native monoclonal antibodies (mAbs) specific to human 3 US 6,956,107 B2 (issued Oct. 18, 2005) (“Fung 107”). 4 US 6,998,468 B2 (issued Feb. 14, 2006) (“Fung 468”). 5 US 6,355,245 B1 (issued Mar, 12, 2002) (“Evans”). 6 US 5,871,734 (issued Feb. 16, 1999) (“Lobb”). 7 US 2001/0036650 A1 (pub. Nov. 1, 2001) (“Li”). 8 US 5,614,370 (issued Mar. 25, 1997) (“Konteatis”). 9 US 6,740,655 B2 (issued May 25, 2004) (“Magee”). 10 US 2002/0172677 A1 (pub. Nov. 21, 2002) (“Lahn”). 3 Appeal 2016-000567 Application 10/655,861 complement component C5 that block complement hemolytic activity and C5a generation.” Evans, Abstr., 1:20-23 (emphasis added); see also id. “Other Publications” (evidencing additional research and reporting on anti-C5 antibody therapy); see also Final Action 7, 10-11 and Answer 3, 10-11 (discussing Evans). FF2. Evans discloses: Human studies, and studies using animal models of human diseases, have implicated the complement system in the pathologies associated with a number of immune complex associated disorders. The activation of complement that mediates the pathology associated with these disorders may be a consequence of an autoimmune mechanism, or can be non- immunologic in origin. Evans 1:50-56; see also Final Action 7, 10-11 and Answer 3, 10-11 (discussing Evans). FF3. Evans discloses: The method of the invention involves the use of preparations containing antibodies to human complement component C5 as pharmaceutical agents. More particularly, the invention provides for the use of anti-C5 antibodies that bind to complement component C5 or active fragments thereof. Preferably, the antibodies block the generation and/or activity of complement components C5a and C5b. For most applications, the antibody is a monoclonal antibody. . . . [And,] it is believed that the anti-C5 antibodies have these and other therapeutic effects through their activity in blocking the generation or activity of the C5a and/or C5b active fragments of complement component C5. Through this blocking effect, the antibodies inhibit the proinflammatory (anaphyla- toxic) effects of C5a and the generation of the C5b-9 membrane attack complex (MAC). Significantly, the blockage effected by the anti-C5 antibodies, since it occurs at the level of complement component C5, has the advantage of maintaining important 4 Appeal 2016-000567 Application 10/655,861 opsonic, anti-infective, and immune complex clearance functions of the complement system mediated by, inter alia, complement component C3. . . . [And,] [t]hese antibodies are useful for the treatment of GN [glomerulonephritis] as well as a number of other conditions. Evans 7:6-44 (emphasis added); see also Final Action 7, 10-11 and Answer 3, 10-11 (discussing Evans). FF4. Evans discloses, “the most preferred antibody of the invention [is] the 5G1.1 antibody.” Evans 7:62—63; see also Final Action 7, 10-11 and Answer 3, 10-11 (discussing Evans). FF5. Evans discloses, “C3a and C5a are anaphylatoxins. These activated complement components can trigger mast cell degranulation, which releases histamine and other mediators of inflammation.” Evans 12:14—17; cf. Spec. 2:5—9; see also Final Action 7, 10-11 and Answer 3, 10-11 (discussing Evans). FF6. Fung 107 discloses: [the] complement [system] is also involved in pathological inflammation and in autoimmune diseases. Therefore, inhibition of excessive or uncontrolled activation of the complement cascade could provide clinical benefit to patients with such diseases and conditions. . . . Activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and C5b-9 membrane attack complexes (MAC), which mediate inflammatory activities involving leukocyte chemotaxis, activation of macrophages, neutrophils, platelets, mast cells and endothelial cells, vascular permeability, cytolysis, and tissue injury. Factor D is a highly specific serine protease essential for activation of the alternative complement pathway. It cleaves 5 Appeal 2016-000567 Application 10/655,861 factor B bound to C3b, generating the C3b/Bb enzyme which is the active component of the alternative pathway C3/C5 convertases. ... In addition, other inflammatory conditions and autoimmune/immune complex diseases are also closely associated with complement activation (V. M. Holers, ibid., B. P. Morgan. Eur. J. Clin. Invest., 1994: 24: 219-228), including thermal injury, severe asthma, anaphylactic shock, bowel inflammation, urticaria, angioedema, vasculitis, multiple sclerosis, myasthenia gravis, membranoproliferative glomerulonephritis, and Sjogren’s syndrome. Fung 107 1:23—2:14 (emphasis added); see also id. Section on Other Publications (evidencing other research and reporting on anti-C5 and anti-C5a antibody therapy); see also Final Action 6, 10 and Answer 3, 9—10 (discussing Fung 107). FF7. Fung 107 discloses: The anti-factor D binding molecules, antibodies, and fragments of this invention can be administered to patients in an appropriate pharmaceutical formulation by a variety of routes, including, but not limited [to] . . . intranasal. . . routes. Such administration enables them to bind to endogenous factor D and thus inhibit the generation of C3b, C3a and C5a anaphylatoxins, and C5b-9. . .. These inhibitors can be used for treatment of diseases or conditions that are mediated by excessive or uncontrolled activation of the complement system. These include, but are [n]ot limited to: (1) tissue damage due to . . . adult respiratory distress syndrome [and] . . . asthma. Fung 107 9:32—63 (emphasis added); see also Final Action 6, 10 and Answer 3, 9-10 (discussing Fung 107). 6 Appeal 2016-000567 Application 10/655,861 FF8. Fung 468 discloses: Since C2a is the catalytic subunit of the C3 and C5 convertases, inhibition of C2 or the C2a portion of C2 would block the activation of C3 and C5. The down-regulation of complement activation has been demonstrated to be effective in treating several disease indications in animal models and in ex vivo studies, e.g.,... adult respiratory distress syndrome [and] . . . severe asthma. Fung 468 2:62—3:21 (emphasis added); see also id. “Other Publications” (evidencing other research and reporting on anti-C5 antibody therapy); see also Final Action 6, 10 and Answer 3, 10 (discussing Fung 468). FF9. Fung 468 discloses intranasal administration of anti-C2a antibodies to inhibit generation of C5a and C5b-9 to treat severe asthma. Fung 468 6:20—51; see also Final Action 6, 10 and Answer 3, 10 (discussing Fung 468). FF10. Lobb is directed to treating asthma using antibody administration and discloses: the study of agents that trigger acute asthmatic episodes supports the theory that asthma is an immunological reaction by a subject in response to specific allergens of the subject’s environment. . . . The inflammatory response in asthma is typical for tissues covered by a mucosa and is characterized by vasodilation, plasma exudation, recruitment of inflammatory cells such as neutrophils, monocytes, macrophages, lymphocytes and eosinophils to the sites of inflammation, and release of inflammatory mediators by resident tissue cells (e.g., mast cells) or by migrating inflammatory cells. (J. C. Hogg, 1990 [7].) In allergen-induced asthma, sufferers often exhibit a dual response to exposure to an allergen—an “early phase” response beginning immediately after exposure and lasting until 1-2 hours after 7 Appeal 2016-000567 Application 10/655,861 exposure, followed by a “late phase” response beginning about 3 hours after exposure and lasting sometimes until 8-10 hours or longer after exposure. (D. W. Cockroft, 1990 [4].) Late phase response in allergen-induced asthma and persistent hyperresponsiveness have been associated with the recruitment of leukocytes, and particularly eosinophils, to inflamed lung tissue. (W. M. Abraham et al., 1988 [8].) Eosinophils are known to release several inflammatory mediators, e.g., 15-HETE, leukotriene C4, PAF, cationic proteins, eosinophil peroxidase. (K. F. Chung, 1990 [9].) Lobb 1:43—2:32; compare Spec. 2:5—9, FF5, and FF6; see also Final Action 7, 10 and Answer 3,11 (discussing Fobb). FF11. Fi and Konteatis also teach generally that C5a, generated by the cleavage of C5, is understood to cause asthma and that antibodies as antagoists are useful in treating asthma. Fi || 6—8, 84, 89, 91—93; Konteatis 13:41—67; see also Final Action 6, 10-11 and Answer 3,10 (discussing Fi and Konteatis). FF12. Magee teaches that asthma is an inflammatory, respiratory and allergic disease/condition. Magee Abstr.; see also Final Action 7, 10-11 and Answer 3,11 (discussing Magee). FF13. Fahn teaches administering an aerosolized antibody to the lungs of an animal to treat asthma. Fahn 126; see also Final Action 7—8, 10, 12 and Answer 3,11 (discussing Fahn). DISCUSSION Obviousness In analyzing patentability and determining obviousness “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int 7 Co. 8 Appeal 2016-000567 Application 10/655,861 v. Teleflex Inc., 550 U.S. 398, 416 (2007). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the answer depends on “whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id. at 417. “If a person of ordinary skill can implement a predictable variation [of a known work], § 103 likely bars its patentability.” Id. “For the same reason, if a technique has been used to improve one device [or process], and a person of ordinary skill in the art would recognize that it would improve similar devices [or processes] in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” Id. “[A] prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant.” In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012). The obviousness analysis “can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR, 550 U.S. at 418. “A person of ordinary skill is also a person of ordinary creativity, not an automaton.” Id. at 421. “In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103.” Id. at 419. We find, in view of the above-cited precedent and noted findings of fact, the Examiner established a prima facie case that the claims would have been obvious. For example, Evans discloses an anti-C5 antibody therapy that treats glomerulonephritis and other inflammatory conditions related to 9 Appeal 2016-000567 Application 10/655,861 the complement system by blocking the cleavage of C5 into C5a and C5b to block their respective anaphylatoxic and membrane attack effects. FF1— FF3, FF5. Evans discloses the anti-C5 antibody 5G1.1 (or h5Gl.l) for this purpose, which is described in the Specification (14:23—15:3) as preferred. FF4. While Evans only indicates that “other inflammatory conditions” in addition to glomerulonephritis can be treated by anti-C5 antibody therapy, the Fung 107 reference discloses that asthma is such an “other inflammatory condition” caused by the complement system and that blocking the production of C5a and C5b-9 by antibody inhibition is useful to treat asthma. FF6—FF7. Likewise, Fung 468 also teaches that blocking activation of C5 using antibodies is effective in treating severe asthma. FF8—FF9. Other references cited in combination with Evans, Fung 107, and Fung 468 also teach how and why inhibiting the cleavage of C5 would be useful to treat asthma. FF10—FF13. Based on the above-referenced and other findings of fact determined by the Examiner and identified in the Final Action and Answer, we conclude that the claimed method is taught and suggested by the cited prior art combination, that there would have been motivation to make the cited prior art combination to achieve the claimed invention, and that there would have been a reasonable likelihood of successfully doing so because doing so amounted to the predictable use of prior art elements according to their established functions. Appellant argues the claims are non-obvious because there was a lack of clarity in the relevant art as of the invention date as to the role of C5 in airway diseases, such as asthma. Br. 8. Further, Appellant argues the prior art taught away from using anti-C5 antibodies to treat respiratory disorders 10 Appeal 2016-000567 Application 10/655,861 such as asthma. Id. at 8—9 (citing Karp11 and Humbles12). Appellant argues Karp is evidence that there was no reason to pursue anti-C5 antibody therapy to treat asthma and that the reference, in fact, teaches away from such therapy because it discloses that inhibition of C5aR reduced IL-12, and IL-12 was evidenced to mitigate allergic asthma in experimental testing, ergo, inhibiting C5aR may worsen allergic asthma. Id. at 8. Appellant also argues Humbles is evidence that reduction in C3aR, which is upstream in the complement cascade from C5, C5a, and C5aR, is shown to mitigate asthma and, therefore, the skilled artisan would have no reason to look to these claimed downstream components for an asthma treatment. Id. at 9. This argument is not persuasive. In Medichem, our reviewing court explained that “[w]here the prior art contains ‘apparently conflicting’ teachings (i.e., where some references teach the combination and others teach away from it) each reference must be considered ‘for its power to suggest solutions to an artisan of ordinary skill. . . considering] the degree to which one reference might accurately discredit another.’” Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) {quoting In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991)). Further, “[ojbviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success.'1'’ In reKubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (emphasis added). The “case law is clear that obviousness cannot 11 Christopher L. Karp et al., Identification of Complement Factor 5 as a Susceptibility Locus for Experimental Allergic-asthma, 1 Nat. Immunology 221-26 (2000) (“Karp”). 12 Alison A. Humbles et al., A Role for the C3a Anaphylatoxin Receptor in the Effector Phase of Asthma, 406 Nature 998—1001 (2000) (“Humbles”). 11 Appeal 2016-000567 Application 10/655,861 be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). Here, we conclude that, while there is some evidence that inhibiting C5 might, theoretically, worsen asthma (see Karp),13 the balance of evidence (FF1—FF13) establishes that the skilled artisan would have pursued an anti- 05 antibody therapy to treat asthma as claimed and would have had a reasonable expectation of successfully doing so based on the teachings of the prior art. As of the invention date, according to the disclosure of the Specification, anti-C5 antibody therapy was well known and based on the cited prior art it could be used to treat asthma. Appellant also argues non-obviousness by attempting to distinguish the claims over each cited reference individually. Br. 9—11. Appellant contends no reference connects anti-C5 antibodies to asthma. Id. at 11. This argument is also not persuasive. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. [The references] must be read, not in isolation, 13 Humbles, unlike Karp, does not support Appellant’s contentions. Humbles discloses research into the relevance of C3a/C3aR to allergic asthma and identifies that C5a is well defined as involved in allergic disease Humbles 998. It is not clear from Humbles that Appellant’s argument, i.e., “Humbles clearly would have led one of ordinary skill in the art to believe that complement factors (e.g., C3a) upstream of C5a are involved in airway hyperresponsiveness, and thus that inhibition of C5a alone would not be effective to prevent the condition,” is supported by the reference. Br. 9. In any event, the claims relate to an anti-C5 antibody therapy, not an anti-C5a antibody therapy. 12 Appeal 2016-000567 Application 10/655,861 but for what [they] fairly teach [] in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Here, the rejection is based on a combination of prior art, which teaches and suggests that anti-C5 antibody therapy is useful in treating diseases, such as severe asthma, caused by or related to the complement system immune response. FF1—FF13. Appellant also argues the Examiner’s rejection is based on the position that anti-C5 antagonists and anti-C5a antagonists are equivalent. Br. 12. Appellant contends that the Wang Declaration14 establishes that inhibiting C5 rather than C5a is superior and, so, they are not equivalent. Id. 12—14. This argument is not persuasive. The claims are directed to “an anti-C5 antibody” and the prior art teaches and suggests an asthma therapy using an anti-C5 antibody. The equivalency of C5 and C5a in relation to causing or treating asthma is not of significance in view of the prior art references, which teach inhibiting the conversion of C5 into C5a and C5b components to treat inflammatory related diseases, such as asthma. The record does not support that the Examiner has premised the obviousness rejection on the equivalence of C5 and C5a inhibition/effects. Answer 13. Further, we note that, while the Wang Declaration identifies that a therapy using anti-C5 antibodies was superior in some respect to a therapy using anti-C5a antibodies in treating asthma, neither the Wang Declaration nor the Appellant’s Brief states that these results would have been 14 Declaration under 37 CFR § 1.132 of Yi Wang (dated Mar. 6, 2014) (“Wang Decl.”). 13 Appeal 2016-000567 Application 10/655,861 unexpected or surprising to the skilled artisan at the time of the invention as compared the closest prior art. For the reasons above, we affirm the obviousness rejection. Obviousness-type Double Patenting Because Appellant presents no arguments pertaining to the Examiner’s double patenting rejection (Br. 5), we summarily sustain the rejection. See MPEP § 1205.02, 9th ed., Rev. 7, Nov. 2015. SUMMARY The obviousness rejection is affirmed. The obviousness-type double patenting rejection is affirmed. 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 14 Copy with citationCopy as parenthetical citation