INNOVATIVE MED CONCEPTS, LLC

Patent Trials and Appeals BoardApr 27, 2021

2020001671 (P.T.A.B. Apr. 27, 2021)

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. 14/494,170 09/23/2014 William L. Pridgen 16210-000008-US-COA 1188 28997 7590 04/27/2021 Harness Dickey (St. Louis) 7700 Bonhomme, Suite 400 St. Louis, MO 63105 EXAMINER LEE, ANDREW P ART UNIT PAPER NUMBER 1628 NOTIFICATION DATE DELIVERY MODE 04/27/2021 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): bkamer@hdp.com stldocket@hdp.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte WILLIAM L. PRIDGEN ____________ Appeal 2020-001671 Application 14/494,1701 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, CHRISTOPHER G. PAULRAJ, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a “drug- combination comprising valac[y]clovir and celecoxib” and a “kit presentation . . . includ[ing] only the combination of valac[y]clovir and celecoxib as active ingredients.” The Examiner rejected the claims on appeal under 35 U.S.C. § 103(a) as obvious. We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. According to Appellant, the real party in interest is Innovative Med Concepts, Inc. Appeal Br. 3. Appeal 2020-001671 Application 14/494,170 2 STATEMENT OF THE CASE The Specification discloses that “[t]he present invention . . . embrac[es] treatment of functional somatic syndromes (FSS).” Spec. ¶ 71. FSS “may be defined as conditions ‘characterized by patterns of persistent bodily complaints for which adequate examination does not reveal sufficiently explanatory structural or other specified pathology.’” Id. ¶ 82. “A diverse number of conditions are commonly described as FSS, including: fibromyalgia, irritable bowel syndrome, [and] chronic fatigue syndrome . . .” Id. The Specification discloses “combination therapy . . . based in part on the discovery that the combination of an antiviral compound and a COX-2 inhibitor will increase efficacy in the treatment of these conditions.” Id. ¶ 85. “In one embodiment, there is provided a combination comprising a therapeutically-effective amount of valac[y]clovir and a therapeutically- effective amount of celecoxib.” Id. ¶ 31. Claims 50–66 are on appeal. Claim 50 is representative and reads as follows: 50. A fixed-dose drug-combination comprising valac[y]clovir and celecoxib, wherein valac[y]clovir and celecoxib are each present in a dosage amount capable of obtaining a co-acting fibromyalgia-treatment outcome, or a co- acting chronic-fatigue-syndrome-treatment outcome, or a co- acting irritable-bowel-syndrome-treatment outcome, wherein the fixed-dose drug-combination includes only the combination of valac[y]clovir and celecoxib as active ingredients. Appeal Br. 15. Appeal 2020-001671 Application 14/494,170 3 The Examiner rejected claims 50–66 under 35 U.S.C. § 103(a) as obvious over the combination of Jain,2 Lerner,3 and Aaron.4 FINDINGS OF FACT FF1. Jain is authored by an “Expert Medical Consensus Panel representing treating physicians, teaching faculty, and researchers” assembled to “establish an expert consensus toward a working case definition of FMS [fibromyalgia syndrome] and a working guide to its management for physicians in Canada.” Jain 4. FF2. Jain provides “an overview of some of the medications, which members of the panel have found helpful for some patients in their clinical practice.” Id. at 29. Celecoxib is identified as one of many such medications for pain in patients suffering from fibromyalgia. Id. at 30–33. FF3. With respect to the pharmacological treatments listed in Jain, “[w]here possible, the level of evidence [supporting the listed treatments] is indicated.” Id. at 30. The “level of evidence” is divided into the following five categories: I. Large double blind randomized, control trials [RCTsl, or meta-analyses of smaller RCTs, clinically relevant out- comes II. Small RCTs, non-blinded RCTs, RCTs using valid surrogate markers 2 Anil Kumar Jain et al., Fibromyalgia Syndrome: Canadian Clinical Working Case Definition, Diagnostic and Treatment Protocols – A Consensus Document, 11(4) J. Musculoskeletal Pain 3–107 (2003) (“Jain”). 3 A. Martin Lerner et al., Valacyclovir Treatment in Epstein-Barr Virus Subset Chronic Fatigue Syndrome: Thirty-six Months Follow-up, 21 In Vivo 707–14 (2007) (“Lerner”). 4 Leslie A. Aaron et al., Overlapping Conditions Among Patients with Chronic Fatigue Syndrome, Fibromyalgia, Temporomandibular Disorder, 160 Arch. Intern. Med. 221–27 (2000) (“Aaron”). Appeal 2020-001671 Application 14/494,170 4 III. Non-randomized controlled studies, observational [cohort] studies, case-control studies, or cross-sectional studies IV. Opinion of expert committees or respected authorities V. Expert opinion Id. Jain explains that “[t]he clinician should be most influenced to try medications for the treatment of FMS symptoms if the medication is supported by ‘levels of evidence’ [LE] I to III.” Id. The use of celecoxib to treat pain in fibromyalgia patients is identified as being supported by the lowest level of evidence – “V,” expert opinion. Id. at 31. FF4. Jain groups medications into medications that show “positive effects” and those that show “mixed effects.” Jain 30. The use of celecoxib to treat pain in fibromyalgia patients is identified as showing “mixed effects.” Id. at 31. FF5. Appellant argues, and the Examiner does not dispute, that celecoxib is a non-steroidal anti-inflammatory drug (“NSAID”). Appeal Br. 8. FF6. Clauw5 teaches that “[d]rugs frequently used to treat peripheral pain such as nonsteroidal anti-inflammatory drugs, opioids, and corticosteroids do not effectively treat fibromyalgia pain.” Clauw 1551. FF7. Derry6 teaches: 5 Daniel J. Clauw, Fibromyalgia, a Clinical Review, 311(15) JAMA 1547– 55 (2014) (“Clauw”). Clauw was cited by Appellant as evidence that “many of the drugs reported in Jain . . . have been found on subsequent inspection not to help fibromyalgia pain.” Appeal Br. 7. 6 Sheena Derry et al., Oral Nonsteroidal Anti-Inflammatory Drugs for Fibromyalgia in Adults, 3 Cochrane Database of Systemic Reviews Art. No.: CD012332 (2017) (“Derry”). Derry was cited by Appellant as evidence that “many of the drugs reported in Jain . . . have been found on subsequent inspection not to help fibromyalgia pain.” Appeal Br. 7. Appeal 2020-001671 Application 14/494,170 5 There is only a modest amount of very low-quality evidence about the use of NSAIDs in fibromyalgia, and that comes from small, largely inadequate studies with potential risk of bias. That bias would normally be to increase the apparent benefits of NSAIDs, but no such benefits were seen. Consequently, NSAIDs cannot be regarded as useful for treating fibromyalgia. Derry 2. FF8. Kendall7 discloses a study that “observed no effect difference between valacyclovir and placebo on overall pain intensity and global tenderness to moderate pressure in patients with FM [fibromyalgia] not having current herpes infection.” Kendall 784. Kendall further discloses “we cannot exclude that valacyclovir might have an effect in patients with current viral infection and FM symptoms.” Id. FF9. The inventor, Dr. William L. Pridgen attests that, in his clinical experience, treating fibromyalgia patients with NSAIDs does not provide “significant relief” to the patients. Pridgen Decl. ¶ 7.8 Dr. Pridgen also attests, that in his clinical experience, celecoxib monotherapy did not provide effective relief for fibromyalgia pain. Id. Dr. Pridgen opines that this experience is consistent with other studies showing that NSAIDs are not effective in treating fibromyalgia pain. Id. ¶¶ 7, 8, 10 (citing Derry, Quijada-Carrera et al., Comparison of Tenoxicam and Bromazepan in the Treatment of Fibromyalgia: A Randomized, Double-Blind, Placebo- Controlled Trial, 65(2-3) Pain 221–25 (1996), and Mahagna et al., A 7 Sally Aspegren Kendall et al., No Effect of Antiviral (Valacyclovir) Treatment in Fibromyalgia: A Double Blind, Randomized Study, 31(4) J. Rheumatol. 783–84 (2004) (“Kendall”). Kendall was cited by Appellant as evidence that it was “known in the art that valac[y]clovir monotherapy, as described by Lerner, is ineffective in treating fibromyalgia.” 8 Declaration of Dr. William L. Pridgen, M.D. submitted under 37 C.F.R. § 1.132 dated November 7, 2018 (“Pridgen Decl.”). Appeal 2020-001671 Application 14/494,170 6 Randomized, Double-Blinded Study Comparing Giving Etoricoxib vs. Placebo to Female Patients with Fibromyalgia, 70(2) Int. J. Clin. Pract. 163–70 (2016)). FF10. Dr. Pridgen attests that, in his clinical experience, treating fibromyalgia patients with antivirals, including with valacyclovir, “did not provide acceptable relief from FM pain.” Pridgen Decl. ¶ 5. Dr. Pridgen opines that this experience is consistent with the other’s reported clinical experience. Id. ¶ 6 (citing Kendall). FF11. Dr. Pridgen attests that treating patients with “naproxen + antiviral,” “ibuprofen + antiviral,” and “nabumetone + antiviral” did not provide “significant FM relief” but when these same patients were “switched to celecoxib + antiviral” they “reported acceptable relief.” Pridgen Decl. ¶ 11 (emphasis omitted). Dr. Pridgen attests: Through a process of trying different COX inhibitors, discontinuing those that did not work and continuing the ones that did, I eventually found that a majority of my patients were finding significant and durable relief from FM pain from just three COX inhibitors: celecoxib, meloxicam, and diclofenac, in combination with a specific antiviral (famciclovir, acyclovir, or valacyclovir). Id. ¶ 12. ANALYSIS In rejecting claims 50–66 as obvious, the Examiner finds that Jain disclosed “administration of 200 mg of celecoxib for the treatment of pain associated with fibromyalgia” and that Lerner taught “the treatment of chronic fatigue syndrome using valacyclovir . . . administered in an amount of 500 mg twice daily.” Ans. 3–4. The Examiner finds that it would have Appeal 2020-001671 Application 14/494,170 7 been obvious to combine valacyclovir with celecoxib because Aaron teaches that “chronic fatigue syndrome and fibromyalgia share key symptoms.” Id. at 8. The Examiner also finds that it would have been obvious to administer the claimed combination “to treat patients suffering from CFS with FM, which, as taught by Aaron, is 80% of CFS patients.” Id. Appellant argues that, when considered with disclosures in the prior art teaching the ineffectiveness of non-steroidal anti-inflammatory drugs, like celecoxib, the disclosure in Jain provides insufficient reason to combine use celecoxib in a single fixed dose treatment. As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): “[T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability.” Appellant has persuaded us that the Examiner has not carried the burden of establishing that the claimed invention would have been obvious over the cited art. The Examiner’s rationale for combining celecoxib and valacyclovir rests on the finding that the ordinary artisan would have used celecoxib to treat pain in patients with fibromyalgia. Ans. 4 (“One of ordinary skill in the art would have been motivated to combine the administration of valacyclovir and celecoxib to treat the overlapping symptoms of pain and fatigue common in chronic fatigue syndrome and fibromyalgia.”); 8 (“One of ordinary skill in the art would thus be motivated to administer valacyclovir for the treatment of fatigue that occurs in patients that have been diagnosed with CFS and fibromyalgia, and combine valacyclovir with celecoxib to treat the attendant symptom of pain in fibromyalgia”); 8–9 (“[O]ne of ordinary skill in the art would have been motivated to administer Appeal 2020-001671 Application 14/494,170 8 valacyclovir for its therapeutic value in treating CFS symptoms and also administer celecoxib for its therapeutic value for pain in FM.”). We recognize that Jain identifies celecoxib as one of many potential treatments for pain in patients suffering from fibromyalgia. FF2. However, this teaching is supported by Jain’s lowest level of evidence – level of evidence V (FF3) – which Appellant aptly describes as amounting to little more than “the unsupported opinion of one of the panel members that celecoxib could be useful for treating fibromyalgia pain.” Reply Br. 2; see FF1–FF3. Moreover, Jain’s expert opinion on celecoxib is not that it has positive effects, but that it provides “mixed effects.” FF4. In sum, Jain provides at best a weak expectation that celecoxib would be effective in treating pain in patients with fibromyalgia. Jain’s disclosure must be considered together with the evidence identified by Appellant that NSAIDs, like celecoxib (FF5), were thought to be ineffective in treating fibromyalgia pain. In particular, Clauw teaches that NSAIDs “do not effectively treat fibromyalgia pain” and Derry teaches that “NSAIDs cannot be regarded as useful for treating fibromyalgia.” FF6, FF7. In addition, Dr. Pridgen testifies that in his clinical experience, which he finds to be consistent with the experience of others in the field, treating fibromyalgia patients with NSAIDs does not provide “significant relief” to the patients. FF9. Indeed, the evidence of record supports that celecoxib provides relief from fibromyalgia pain only when it is combined with valacyclovir or one of two additional antivirals. FF9, FF11.9 9 The evidence of record also supports that valacyclovir does not provide fibromyalgia pain relief when administered in monotherapy. FF8, FF10. Appeal 2020-001671 Application 14/494,170 9 Considering the evidence of record as a whole, the preponderance of the evidence does not support a conclusion that the ordinary artisan would have had reason to use celecoxib in a fixed dose combination with valacyclovir. Absent a persuasively supported reason for combining celecoxib and valacyclovir, we determine that the Examiner has not carried its burden to show that claims 50–66 would have been obvious over the cited art. Accordingly, we reverse the Examiner’s rejection of claims 50–66. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 50–66 103(a) Jain, Lerner, Aaron 50–66 REVERSED