Lanny Johnson

Patent Trials and Appeals Board

Jan 20, 2022

2021004776 (P.T.A.B. Jan. 20, 2022)

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. 15/585,697 05/03/2017 Lanny Leo Johnson P60557U 4805 160962 7590 01/20/2022 Stonebridge IP, PLLC 10432 Balls Ford Rd Suite 300 Manassas, VA 20109 EXAMINER HANLEY, SUSAN MARIE ART UNIT PAPER NUMBER 1653 NOTIFICATION DATE DELIVERY MODE 01/20/2022 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): eofficeaction@appcoll.com info@stonebridgeip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte LANNY LEO JOHNSON __________ Appeal 2021-004776 Application 15/585,697 Technology Center 1600 __________ Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and RACHEL H. TOWNSEND, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to a method of intra-articular injection of cyanidin-3-glucoside (C3G) to a subject with an osteoarthritic joint. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm but designate our affirmance as a new ground of rejection. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as the inventor Lanny Leo Johnson (see Appeal Br. 3). We have considered the Specification of May 3, 2017 (“Spec.”); Final Office Action of Sept. 1, 2020 (“Final Act.”); Appeal Brief of Apr. 21, 2021 (“Appeal Br.”); and Examiner’s Answer of June 3, 2021 (“Ans.”). Appeal 2021-004776 Application 15/585,697 2 Statement of the Case Background “Osteoarthritis (OA) affects nearly 27 million Americans and poses significant costs on both the patient’s health and finances” (Spec. 1:23-24). In osteoarthritis, the cartilage of the superficial zone begins to deteriorate as OA progresses triggering an irreversible process that eventually leads to the loss of underlying layers of cartilage. The integrity of the cartilage breaks down resulting in fragments of cartilage being dispersed in the joint causing reaction of the joint lining, inflammation and the symptoms of pain and swelling. Over time, exposed bone surfaces begin to grind painfully against one another. (id. at 2:13-18). “[T]he present invention provides methods and compositions that stimulate or induce cartilage repair or regeneration while protecting against cell death or degradation of cartilage” (id. at 11:19-21). The Claims Claims 1, 2, 6-13, 16, 23, 26, 27, and 30-37 are on appeal.2 Independent claim 1 is representative and reads as follows: 1. A method of modifying the disease of osteoarthritis in a subject having an osteoarthritic joint, the method comprising: administering a composition into an osteoarthritic joint of the subject by an intra-articular injection, wherein the composition comprises Cyanidin-3-Glucoside (C3G) and a pharmaceutically acceptable carrier. 2 We note that claim 36 is not subject to any rejection and is allowed by the Examiner (see Appeal Br. 3). Appeal 2021-004776 Application 15/585,697 3 The Issues A. The Examiner rejected claims 1, 2, 6, 7, 10, 12, 13, 16, 26, 30, 32, and 34 under 35 U.S.C. § 103(a) as obvious over Jean,3 Reddy,4 and Alberte5 (Final Act. 3-6). B. The Examiner rejected claims 1, 2, 6-13, 16, 23, 26, 27, 30-35, and 37 under 35 U.S.C. § 103(a) as obvious over Jean, Reddy, Alberte and Kimura6 (Final Act. 6-14). A. 35 U.S.C. § 103(a) over Jean, Reddy, and Alberte The Examiner finds Jean studied “the effect of intra-articular injection . . . of the cyclooxygenase (COX-2) inhibitor parecoxib into the osteoarthritic (OA) joints” and teaches “inhibition of COX-2 provides analgesic and anti-inflammatory effects” (Final Act. 3-4). The Examiner acknowledges that Jean does not teach “the intra-articular administration of cyanidin-3-glucoside” (id. at 4). The Examiner finds Reddy teaches “cyanidin-3-glucoside at a concentration of 100 pg/ml (0.1 X 10-6 mg/ml) is both a COX-1 and COX-2 inhibitor (Final Act. 4). The Examiner finds “Alberte teaches that C3G is a 3 Jean et al., Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates osteoarthritis progression in anterior cruciate ligament-transected knee in rats: role of excitatory amino acids, 15 OsteoArthritis Cartilage 638-45 (2007). 4 Reddy et al., Relative Inhibition of Lipid Peroxidation, Cyclooxygenase Enzymes, and Human Tumor Cell Proliferation by Natural Food Colors, 53 J. Agric. Food Chem. 9268-73 (2005). 5 Alberte et al., US 2007/0248700 A1, published Oct. 25, 2007. 6 Kimura et al., US 4,997,850, issued Mar. 5, 1991. Appeal 2021-004776 Application 15/585,697 4 water soluble polyphenol” (id.). The Examiner finds it would have been obvious to select cyanidin-3-glucoside for treatment of osteoarthritic joints “because each composition (C3G and Parecoxib) is known to have the same function, to function as a COX-2 inhibitor and COX-2 inhibitors are associated with decreased inflammation and inhibition of cartilage degeneration of the medial femoral condyle. Hence, the substitution is no more than the predictable use of prior art elements” (id. at 5). Appellant contends “compositions that are both COX-1 and COX-2 inhibitors are not, and were not, understood at the time of filing this application to be known mediators of inflammation” and that “it is well known in the art that COX-2 inhibitors are mediators of inflammation while COX-1 inhibitors are known to be associated with side effects to be avoided” (Appeal Br. 8). Appellant contends that Jean teaches away from COX-1 inhibitors because “[c]onventional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2 at standard anti- inflammatory dose and this dual inhibition leads to a number of side effects, in particular gastrointestinal ulceration” (id. at 9; citing Jean 639, col. 1; emphasis omitted). The Examiner responds that the “combination of Reddy and Jean make obvious intra-articular injection of C3G into a synovial joint which will not have a systemic effect” (Advisory Act. 4). Appellant responds that “[t]here is in fact no evidence of record in this application, other than the Examiner’s statement in the advisory action, that intra-articular injection of C3G into a synovial joint . . . would not have a systemic effect” (Appeal Br. 10). Appellant further contends that Jean “teaches that dual COX-1 and COX-2 inhibitors are undesirable for the Appeal 2021-004776 Application 15/585,697 5 treatment of osteoarthritis through intra-articular injection in direct contradiction to the office’s assertion” (id.). Appellant contends the “prior art expressly teaches that the pursuit of a dual COX-1 and COX-2 inhibitor (such as C3G) would be unlikely to be productive of the results sought by Appellant since dual COX-1 and COX-2 inhibitors would be expected to exhibit significant side effects” (id. at 12). The issue with respect to this rejection is whether a preponderance of the evidence of record supports non-obviousness based on a teaching away from using the Cox-1 inhibitor cyanidin-3-gluclose based on systemic side effects? Findings of Fact 1. Jean teaches “we examined the effects of intra-articular injection of the COX-2 inhibitor parecoxib on the progression of OA and EAA changes” (Jean 639, col. 1). 2. Jean teaches “[p]arecoxib, a water-soluble prodrug of the oral formulation valdecoxib, is approximately 28,000-fold more potent against COX-2 than against COX-1” (Jean 639, col. 1). 3. Jean teaches “that intra-articular injection of the COX-2 inhibitor parecoxib attenuates the progression of OA in ACLT rats” (Jean 643, col. 1). 4. Jean teaches “[s]elective COX-2 inhibitors are effective for OA treatment by attenuating synovial inflammation and cartilage destruction” (Jean 644, col. 1). 5. Jean teaches “[c]onventional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2 at standard anti- Appeal 2021-004776 Application 15/585,697 6 inflammatory dose and this dual inhibition leads to a number of side effects, in particular gastrointestinal ulceration” (Jean 639, col. 1). 6. Reddy teaches: Cyclooxygenase enzymes, COX-1 and COX-2, catalyze the conversion of arachidonic acid to generate chemical mediators of inflammation. Antiinflammatory drugs, ibuprofen (2.52 μg/mL), aspirin (180 μg/mL), Vioxx (1.67 μg/mL), and Celebrex (1.67 μg/mL), used as positive controls, gave 51, 40; 78, 99; 63, 32; and 0.7, 82% of COX-1 and COX-2 enzymes inhibition, respectively. (Reddy 9270, col. 2). 7. Figure 3, panel b of Reddy is reproduced below: Figure 3, panel “(b) betanin (100 μg/mL), cyanidin-3-O-glucoside (100 μg/mL), and a mixture of betanin + cyanidin-3-O-glucoside (100 μg/mL). The vertical bars represent the standard deviation of each data point (n = 2).” Reddy specifically teaches cyanidin-3-O-glucoside inhibits Cox-2 by 59% and Cox-1 by 29.5% (see Reddy 9270, col. 2-9271, col. 1). 8. Alberte teaches that cyanidin-3-glucoside is “(a water soluble polyphenolic of elder species)” (Alberte ¶ 127). Appeal 2021-004776 Application 15/585,697 7 9. Knorth7 teaches inflamed and not healthy synovium represents the target tissue of COX inhibitors in the therapy of OA in vivo. It should be noted that with regard to this target tissue, at least in vitro, our study could demonstrate a substantial participation of synovial COX-1 in the release of the pro-inflammatory eicosanoid PGE2. (Knorth 665, col. 1). 10. Knorth teaches Our study suggests that, at least in vitro, at COX-2- specific concentrations, selective COX-2 inhibitors might be inferior compared to non-selective COX inhibitors in suppressing PGE2 formation in OA synovitis tissue. With respect to the anti-inflammatory therapy of OA with selective COX-2 inhibitors in vivo, the relative contribution of COX-1 in synovitis should be considered, weighing the therapeutic potency of COX-unspecific NSAID against the assumed superior gastrointestinal safety profile of COX-2 inhibitors. (Knorth 665, col. 1). Principles of Law In Gurley, the court found that the “degree of teaching away will of course depend on the particular facts” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). And in Medichem, the 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 . . . consider[ing] the degree to which one reference might accurately 7 Knorth et al., Participation of cyclooxygenase-1 in prostaglandin E2 release from synovitis tissue in primary osteoarthritis in vitro, 12 OsteoArthritis and Cartilage 658-66 (2004). Appeal 2021-004776 Application 15/585,697 8 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)). Analysis Consistent with Medichem and Gurley, we balance the evidence supporting obviousness with the conflicting evidence. The Examiner establishes a reasonable case of prima facie obviousness based on Jean’s teaching to treat an osteoarthritic joint by intra-articular injection of a Cox-2 inhibitor parecoxib and Reddy’s teaching that cyanidin-3-O-glucoside also inhibits Cox-2 and is therefore an obvious equivalent of parecoxib that would be useful in intra-articular injection to treat an osteoarthritic joint (FF 1-7). Appellant responds that cyanidin-3-O-glucoside is not an obvious equivalent because it also has Cox-1 inhibitory activity (FF 7) and therefore the prior art teaches away from the combination because Jean suggests that the Cox-1 inhibitory activity of cyanidin-3-O-glucoside would be expected to have “a number of side effects, in particular gastrointestinal ulceration” (FF 5). While we agree with Appellant that the Examiner’s finding of no systemic effects in the advisory action lacks evidentiary support, the Examiner appears to have withdrawn this line of reasoning in the Answer. Appellant also provides no evidence, as opposed to argument, that the Cox-1 inhibitory activity of cyanidin-3-O-glucoside when injected would result in clinically relevant side effects. Thus, the evidence of record slightly favored the Examiner’s position as the teaching away when balanced with the teaching in favor of obviousness supports a finding of obviousness. Appeal 2021-004776 Application 15/585,697 9 We note that neither the Examiner nor Appellant addressed whether inhibition of Cox-1, along with Cox-2, would be beneficial for treatment of osteoarthritis. If Cox-1 inhibition would be beneficial, it would provide a persuasive reason to substitute the Cox-2 specific inhibitor parecoxib with the less selective inhibitor cyanidin-3-O-glucoside that inhibits both Cox-1 and Cox-2 (FF 7). In order to address this question, we undertook a limited literature search to determine if Cox-1 also played a role in osteoarthritis. We identified the prior art Knorth reference, which teaches that in inflamed arthritic tissue, “our study could demonstrate a substantial participation of synovial COX-1 in the release of the pro-inflammatory eicosanoid PGE2” (FF 9). Knorth’s teaching supports the Examiner’s obviousness position by providing a reason to use a compund that inhibits both Cox-1 and Cox-2, to reduce release of pro-inflammatory compounds in osteoarthritic joints. Knorth further recognizes the balancing concerns between systemic side effects and Cox-1 inhibition, stating that “[w]ith respect to the anti- inflammatory therapy of OA with selective COX-2 inhibitors in vivo, the relative contribution of COX-1 in synovitis should be considered, weighing the therapeutic potency of COX-unspecific NSAID against the assumed superior gastrointestinal safety profile of COX-2 inhibitors” (FF 10). Based on all of the prior art of record, we conclude that the balance of the evidence reasonably suggests that treatment of both Cox-1 and Cox-2 would have been expected to provide superior treatment of osteoarthritis in an osteoarthitic joint because both Cox-1 and Cox-2 are associated with inflammation of such a joint (FF 9-10). And the teaching away concern about systemic effects of Cox-1 lacks specific evidence showing that doses Appeal 2021-004776 Application 15/585,697 10 of cyanidin-3-O-glucoside would have been expected to have such systemic side effects and that the ordinary artisan, in selecting obvious dosing amounts, would not have reasonably been able to select optimized doses sufficient to treat disease without causing significant systemic side effects. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955). Thus, we conclude the known benefits of Cox-1 inhibition in osteoarthritis outweights the undisclosed and possibly absent side effects of a Cox-1 inhibitor such as cyanidin-3-O-glucoside. Because we rely upon an additional reference not cited by the Exmainer and because our reasoning differs from that of the Examiner, we designate our analysis as a new ground of rejection in order to afford Appellant the opportunity to provide rebuttal evidence and arguments. Conclusion of Law A preponderance of the evidence of record supports obviousness of treatment of osteoarthritic joints with intra-articular injection of cyanidin-3- O-glucoside. B. U.S.C. § 103(a) over Jean, Reddy, Alberte and Kimura Appellant does not separately argue this obviousness rejection, instead relying upon their arguments to overcome the combination of Jean, Reddy, and Alberte (see Appeal Br. 12-13). Having affirmed the obviousness of claim 1 for the reasons given above, we also find that the further combination renders the rejected claims obvious for the same reasons and also designate this rejection as a new grounds. Appeal 2021-004776 Application 15/585,697 11 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed New Ground 1, 2, 6, 7, 10, 12, 13, 16, 26, 30, 32, 34 103 Jean, Reddy, Alberte, Knorth 1, 2, 6, 7, 10, 12, 13, 16, 26, 30, 32, 34 1, 2, 6-13, 16, 23, 26, 27, 30-35, 37 103 Jean, Reddy, Alberte, Kimura, Knorth 1, 2, 6-13, 16, 23, 26, 27, 30-35, 37 Overall Outcome 1, 2, 6-13, 16, 23, 26, 27, 30-35, 37 This decision contains a new ground of rejection pursuant to 37 C.F.R. § 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 Appeal 2021-004776 Application 15/585,697 12 will be remanded to the examiner. The new ground of rejection is 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 § 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 Manual of Patent Examining Procedure § 1214.01. AFFIRMED; 37 C.F.R. § 41.50(b)