2020006237 (P.T.A.B. May. 20, 2021)

Gary Borodic

Patent Trials and Appeals BoardMay 20, 2021

2020006237 (P.T.A.B. May. 20, 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. 16/013,552 06/20/2018 Gary E. Borodic Borodic 16.01 CON 4367 26812 7590 05/20/2021 HAYES SOLOWAY P.C. 175 CANAL STREET MANCHESTER, NH 03101 EXAMINER FONTAINHAS, AURORA M ART UNIT PAPER NUMBER 1649 NOTIFICATION DATE DELIVERY MODE 05/20/2021 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): KStevens@hayes-soloway.com TSULLIVAN@HAYES-SOLOWAY.COM rchriston@hayes-soloway.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte GARY E. BORODIC ____________ Appeal 2020-006237 Application 16/013,552 Technology Center 1600 ____________ Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and TAWEN CHANG, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals2 from Examiner’s decision to reject claims 1–5 and 7–11 (Appeal Br. 5). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 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 “Gary Borodic” (Appellant’s April 27, 2020, Appeal Brief (Appeal Br.) 3). 2 This Appeal is related to pending Appeal 2021-000918 (Application 15/834,491). Appeal 2020-006237 Application 16/013,552 2 STATEMENT OF THE CASE Appellant’s disclosure relates to “formulations and methods of treating and possibly preventing visual loss from macular degeneration by administering botulinum toxin-based pharmaceuticals” (Spec.3 1:20–21). Appellant’s claim is reproduced below: 1. A method of treating and/or retarding progression of dry macular degeneration in a patient, the method comprising: identifying a patient with dry macular degeneration; and injecting a botulinum neurotoxin into a periorbital or a para orbital region of the patient, but not into an intra- ocular or a subconjunctival region of the patient, wherein the botulinum neurotoxin is botulinum toxin type A and the botulinum neurotoxin injected conforms with conventional dosing, wherein the botulinum neurotoxin is transported by axoplasmic flow into the intra-ocular region of the patient by a nerve fiber conduit and the axoplasmic flow does not subject extra-ocular muscles of the patient to weakening effects of botulinum neurotoxin, wherein injecting the botulinum neurotoxin avoids diplopia and/or ptosis, and wherein injecting the botulinum neurotoxin avoids risk of retinal detachment endophthalmitis, cataract formation, vitreous hemorrhage, retinal break, and glaucoma. (Appeal Br. 26.) 3 Appellant’s June 20, 2018, Specification. Appeal 2020-006237 Application 16/013,552 3 Ground of rejection before this Panel for review:4 Claims 1–5 and 7–11 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of First,5 Donovan,6 Gregori,7 Gross,8 Blumenfeld,9 and Nickla.10 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? 4 Appellant does not contest the provisional rejections of claims 1–5 and 7– 11 under the judicially created doctrine of obviousness-type double patenting as being unpatentable over (a) claims 1, 4–6, 11, 13–19, 26–28, 30–32, 34, 35, and 37 of copending Application No. 15/834,491 (’491) and (b) claims 1–10 and 12–15 of copending Application No. 16/015,984 (’984) (see Examiner’s July 1, 2020, Answer (Ans.) 10 (Examiner finds that “the nonstatutory double patenting rejections of record . . . are not part of the Appeal Brief); see also Appellant’s September 1, 2020, Reply Brief (Reply Br.) 1 (“Appellant is not currently contesting the merits of the obviousness- type double patenting rejection”)). Thus, Appellant waived Appeal of these rejections. Accordingly, we decline to address the merits of the provisional obviousness-type double patenting rejections. See Ex parte Moncla, 95 USPQ2d 1884, 1885 (BPAI 2010) (precedential); see also Ex parte Jerg, Appeal No. 2011-000044, 2012 WL 1375142, at *2–3 (BPAI Apr. 13, 2012) (informative). 5 First, US 7,465,458 B2, issued Dec. 16, 2008. 6 Donovan, US 2004/0170665 A1, published Sept. 2, 2004. 7 Gregori et al., Spectral Domain Optical Coherence Tomography Imaging of Drusen in Nonexudative Age-Related Macular Degeneration, 118 OPHTHALMOLOGY 1373–79 (2011). 8 Gross et al., US 7,146,209 B2, issued Dec. 5, 2006. 9 Blumenfeld, US 8,846,622 B2, issued Sept. 30, 2014. 10 Nickla et al., The multifunctional choroid, 29 PROGRESS IN RETINAL AND EYE RESEARCH 144–68 (2010). Appeal 2020-006237 Application 16/013,552 4 FACTUAL FINDINGS (FF) FF 1. First discloses methods of treating an eye disorder. The methods comprise a step of locally administering a Clostridial toxin to the eye of a patient to treat the disorder. In some embodiments, the methods comprise a step of locally administering a Clostridial toxin to a cornea of a mammal to treat the disorder. For example, a Clostridial toxin may be administered topically to the cornea to treat the eye disorder. In some embodiments, the Clostridial toxin is administered with a vasoconstrictor. (First 3:18–26; see id. at Abstract, 1:12–16; see also Ans. 5). FF 2. First discloses: In some embodiments, a Clostridial toxin is locally administered to the eye to treat the eye disorder. The Clostridial toxin may be locally administered to the cornea of the eye. In one embodiment, the Clostridial toxin is administered topically to treat the eye disorder. For example, the Clostridial toxin may be administered topically to the cornea of the eye. (First 4:51–56; see also id. at 15:59–16:22 (First exemplified a method of treating “Macular Edema (Cystoid Macular Edema)” comprising “topically administering to the patient’s eye a composition comprising a Clostridial toxin, e.g. about 1 unit of a botulinum toxin type A.”); Ans. 5.) FF 3. First discloses: [C]ompositions that may be employed for treating an eye disorder. In accordance with the present invention, the compositions comprise an ophthalmically acceptable carrier, a Clostridial toxin in an amount effective to treat an eye disorder when the composition is administered to an eye, and a polyanionic component in an amount effective to provide lubrication to an eye when the composition is administered to an eye. In some embodiments, the composition is a solution. In some embodiments, the Clostridial toxin may be a toxin produced by a . . . Clostridial botulinum. In some Appeal 2020-006237 Application 16/013,552 5 embodiments, the Clostridial toxin may be a botulinum toxin type A, B, C1, D, E, F, G and/or mixtures thereof. In some embodiments, the Clostridial toxin is a botulinum toxin type A. (First 3:34–48; see also id. at 1:48–49 (First discloses that the “Clostridial toxin . . . commonly used clinically to treat various muscular conditions is botulinum toxin”); see generally Ans. 5.) FF 4. First discloses that “botulinum toxins may . . . have inhibitory effects in the central nervous system” and “that botulinum toxin is able to ascend to the spinal area by retrograde transport. As such, a botulinum toxin injected at a peripheral location, for example intramuscularly, may be retrograde transported to the spinal cord” (First 2:45–53; see also Donovan ¶ 66 (Donovan discloses that “botulinum toxin is able to ascend to the spinal area by retrograde transport” and, thus, “a botulinum toxin injected at a peripheral location, for example intramuscularly, may be retrograde transported to the spinal cord”); Ans. 4, 6). FF 5. First discloses that “botulinum toxins exhibit a high, specific affinity for gangliocide receptors on the surface of presynaptic cholinergic neurons,” wherein “receptor mediated endocytosis of botulinum toxin by peripheral cholinergic neurons results in little if any retrograde transport, inhibition of acetylcholine exocytosis from the intoxicated peripheral motor neurons and a flaccid paralysis” (First 10:66–11:8; see also Donovan ¶ 69 (Donovan discloses that “receptor mediated endocytosis of botulinum toxin by peripheral cholinergic neurons results in little if any retrograde transport, inhibition of acetylcholine exocytosis from the intoxicated peripheral motor neurons and a flaccid paralysis”)). Appeal 2020-006237 Application 16/013,552 6 FF 6. First discloses: In some embodiments, the eye disorder is associated with an inflammation of the eye. Examples of eye disorders associated with an inflammation include, but are not limited to, bacterial conjunctivitis, fungal conjunctivitis, viral conjunctivitis, uveitis, keratic precipitates, macular edema, and inflammation response after intra-ocular lens implantation. (First 4:4–9.) FF 7. Examiner finds that First fails to disclose the treatment of “dry macular degeneration by administering treatment as a periorbital or para orbital injection” (Ans. 5; cf. id. at 4 (Examiner relies on First “to teach that the art has already contemplated treating age-related macular degeneration (AMD) with botulinum neurotoxin.”)). FF 8. Donovan discloses “[a] biodegradable botulinum toxin ocular implant for treating a medical condition of the eye upon implantation of the implant into the vitreous chamber of a patient’s eye” (Donovan, Abstract; id. ¶¶ 31–34, 41, 45, 46 (Donovan discloses that a botulinum toxin within the scope of its disclosure includes botulinum toxin type A); see Ans. 6). FF 9. Donovan discloses “macular degeneration” an “[e]xample[] of [a] medical condition[] of the eye which may be treated by . . . [its disclosed] implants and methods” (Donovan ¶ 234; see id. ¶ 4 (Donovan discloses that an ocular disorder within the scope of its disclosure includes “macular degeneration”); id. ¶ 260 (Donovan discloses that its “intraviteal implant can be used to treat . . . macular degeneration.”); Ans. 4 (Examiner finds that Donovan discloses “using botulinum toxin and specifically botulinum neurotoxin type A, to treat macular degeneration.”)). FF 10. Examiner finds that Donovan does not teach administering botulinum toxin to the sphenopalatine ganglion (SPG) (Ans. 6). Appeal 2020-006237 Application 16/013,552 7 FF 11. Examiner finds that Gregori discloses “that there are two types of macular degeneration, dry and wet macular degeneration; that dry macular degeneration may progress to wet macular degeneration and teaches methods of identifying these specific patient populations” (Ans. 4; see also id. at 6–7 (citing Gregori Abstract, 1373: col. 1; 1374: col. 2, paragraph 4; 1377: col. 1, paragraph 3)). FF 12. Examiner finds that Gregori “does not teach treating macular degeneration with botulinum neurotoxin” (Ans. 7). FF 13. Gross “relates to the use of electrical, chemical, mechanical and/or odorant stimulation for treating eye pathologies” (Gross 1:44–47; see generally Ans. 7). FF 14. Gross discloses: In some preferred embodiments . . . conditions of the eye are treated by stimulating at least one “modulation target site” (MTS) as defined hereinbelow, by applying electrical, chemical, mechanical and/or odorant stimulation to the site. For some conditions, such as some ocular vascular disorders, such stimulation is configured so as to increase cerebral blood flow (CBF), thereby increasing blood flow to various tissues of the eye and treating the condition. Alternatively or additionally, such stimulation is configured to increase permeability of the BBB, in order to enhance delivery of therapeutic molecules from the systemic blood circulation across the BBB and into the eye, so as to treat tumors and other conditions of the eye. The electrical, chemical, mechanical and odorant stimulation techniques described herein may treat a number of eye conditions, including, but not limited to, . . . macular degeneration. . . . [Wherein,] a “modulation target site” (MTS) consists of: A sphenopalatine ganglion (SPG) also called a pterygopalatine ganglion); . . . [and/or] a sphenopalatine nerve. (Gross 5:11–47; see Ans. 7.) Appeal 2020-006237 Application 16/013,552 8 FF 15. Examiner finds that “Gross fails to treat the treatment of botulinum neurotoxin for macular degeneration” (Ans. 7). FF 16. Blumenfeld discloses “[b]otulinum toxin, among other presynaptic neurotoxins is used for the treatment and prevention of migraine and other headaches associated with vascular disorders. Presynaptic neurotoxins are delivered focally, targeting the sphenopalatine ganglion. Exemplary delivery is carried out by way of injection” (Blumenfeld, Abstract; see also id. at 5:22–55; id. at 5:36–37 (Blumenfeld discloses the use of botulinum toxin type A); Ans. 5, 7). FF 17. Blumenfeld discloses that “direct sphenopalatine administration of presynaptic neurotoxins can be used” (Blumenfeld 11:30–31; see generally Ans. 7). FF 18. Examiner finds that “Blumenfeld does not teach treating macular degeneration” (Ans. 7). FF 19. Examiner finds that Nickla discloses “that choroidal vasculature is the major blood supply for the outer retina, and that the choroidal vasculature is involved in AMO. Nickla indicates that the main parasympathetic input to the choroid originates from the pterygopalatine ganglion” (Ans. 7). ANALYSIS Based on the combination of First, Donovan, Gregori, Gross, Blumenfeld, and Nickla, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious To arrive at the claimed invention from the disclosures of First, Donovan, Gregori, Gross, Blumenfeld and Nickla. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because First and Donovan Appeal 2020-006237 Application 16/013,552 9 teach successfully treating macular degeneration, which would include both the wet and dry forms of . . . [age-related macular degeneration (AMO)], with botulinum neurotoxin and Gregori teaches that one would want to treat dry macular degeneration and reduce its advancement/progression to reduce loss of vision in the dry AMO patient population. Gregori, for instance, teaches that dry macular degeneration affects the retina and . . . [retinal pigment epithelium (RPE)] structure of the eye which leads to vision loss. Therefore, one of ordinary skill in the art would be motivated to administer a treatment that has been shown to be successful in treating macular degeneration as demonstrated by First and Donovan [and] . . . it would reasonably be expected that administration of botulinum neurotoxin as provided by the combination of prior art references would necessarily result in one or more of the claimed therapeutic effects, absent evidence to the contrary. (Ans. 8–9.) We are not persuaded. Appellant’s claim 1, reproduced above, requires, inter alia, the injection of a botulinum neurotoxin into a periorbital or a para orbital region of the patient, but not into an intra-ocular or a subconjunctival region of the patient (see Appeal Br. 26). According to Appellant’s claim 1, injection into a periorbital or a para orbital region of the patient results in the transport of botulinum neurotoxin, by axoplasmic flow, into the intra-ocular region of the patient by a nerve fiber conduit and the axoplasmic flow does not subject extra-ocular muscles of the patient to weakening effects of botulinum neurotoxin and avoids diplopia and/or ptosis (id.). Examiner failed to establish that First, Donovan, Gregori, Gross, Blumenfeld, and Nickla alone, or in combination, teach or suggest the administration of botulinum neurotoxin into a periorbital or a para orbital region of the patient (see FF 1–19). The evidence of record does, however, support a finding that “botulinum toxins exhibit a high, specific affinity for Appeal 2020-006237 Application 16/013,552 10 gangliocide receptors on the surface of presynaptic cholinergic neurons,” wherein “receptor mediated endocytosis of botulinum toxin by peripheral cholinergic neurons results in little if any retrograde transport” (FF 5). As Appellant explains, the locus of injection, according to their claim 1, “the paraorbital ganglion[,] contains cholinergic nerves with receptors that mediate endocytosis” (Reply Br. 3 n.1). Given the foregoing, Examiner failed to establish an evidentiary basis on this record that those of ordinary skill in this art, at the time of Appellant’s claimed invention, would have reasonably expected that administration of botulinum neurotoxin into a periorbital or a para orbital region of the patient would have resulted in transport of the botulinum neurotoxin to an intra-ocular region of the patient for the treatment of dry macular degeneration in a patient, as required by Appellant’s claim 1. To the contrary, the evidence of record supports a finding that those of ordinary skill in the art, at the time of Appellant’s claimed invention, would have reasonably expected that botulinum neurotoxin injected into a periorobital or para orbital region of a patient would result in endocytosis of the toxin and little if any retrograde transport (see FF 5; Reply Br. 3 n.1; see also Appeal Br. 17 (Appellant contends that “[i]t is important to note that no cited reference teaches that botulinum toxin (or any other type of neuromuscular blocking agent) can be delivered through remote nerve axoplasm for the treatment of dry macular degeneration.”); Appeal Br. 18 (Appellant contends that because First and Donovan both “point out the lack of . . . [retrograde] transport, and teach that botulinum should be in direct contact, either via topical application, or implant, there would be no motivation to administer a Appeal 2020-006237 Application 16/013,552 11 non-localized injection, as claimed, because the references both indicate the botulinum toxin stays local to the injection site”)).11 Thus, we agree with Appellant’s contention: To combine the teachings of the cited references as proposed by the Examiner, one skilled in the art would have needed to understand that axoplasmic transport of botulinum toxin could occur, as claimed, and that it could be effectively used to treat dry age-related macular degeneration (dAMD). However, axoplasmic transport of botulinum toxin to the inner eye (as claimed) was simply not known prior to the time of invention and therefore this hindsight knowledge cannot be used to bolster the obviousness rationale proposed by the Examiner. (Reply Br. 5; see also id. at 4–5 (Appellant contends that “[a]xoplasmic transport of botulinum toxin to the inner eye was a significant discovery in the field of treating age-related macular degeneration and should not be overlooked.” (emphasis omitted)).) Obviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418, 127 S.Ct. 1727, 167 L.Ed.2d 705 (2007). Rather, obviousness requires the additional showing that a person of ordinary skill at the time of the invention would have selected and combined those prior art 11 We appreciate Examiner’s finding that “botulinum toxin is capable of ascending the spinal cord by retrograde transport (aka axoplasmic flow) when injected from a peripheral location” (Ans. 11, 15), but find that the evidence of record contrasts this transport mechanism with the receptor mediated endocytosis of botulinum toxin by peripheral cholinergic neurons, i.e., those at the injection site recited in Appellant’s claim 1, which results in little if any retrograde transport. Appeal 2020-006237 Application 16/013,552 12 elements in the normal course of research and development to yield the claimed invention. Id. at 421, 127 S.Ct. 1727. Unigene Laboratories, Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011). For the foregoing reasons, the evidence on this record supports a finding that, at the time of Appellant’s claimed invention, a person of ordinary skill in this art would not have selected and combined the prior art in the normal course of research and development to yield Appellant’s claimed invention. See id. For the same reasons, we are not persuaded by Examiner’s assertion that a “person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of” First, Donovan, Gregori, Gross, Blumenfeld, and Nickla (see e.g., Ans. 10). The consistent criterion for determination of obviousness is whether the prior art would have suggested to one of ordinary skill in the art that this process should be carried out and would have a reasonable likelihood of success, viewed in the light of the prior art. Both the suggestion and the expectation of success must be founded in the prior art, not in the applicant’s disclosure. In re Dow Chemical Co., 837 F.2d 469, 473 (Fed. Cir. 1988) (citations omitted). For the reasons set forth above, we find that the evidence on this record fails to provide the requisite suggestion or reasonable likelihood of success and, therefore, we reverse the obviousness rejection on this record. To be complete, we find that because Examiner failed to establish an evidentiary basis on this record to support a conclusion that the combination of First, Donovan, Gregori, Gross, Blumenfeld, and Nickla makes obvious the injection of botulinum toxin as required by Appellant’s claimed invention, we are not persuaded by Examiner’s assertion that Appellant merely “recognized another advantage which would flow naturally from Appeal 2020-006237 Application 16/013,552 13 following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious” (see Ans. 16 (citing Ex parte Obiaya, 227 USPQ 58, 60 (BPAI 1985); MPEP § 2145(II))). CONCLUSION The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness. The rejection of claims 1–5 and 7–11 under 35 U.S.C. § 103(a) as unpatentable over the combination of First, Donovan, Gregori, Gross, Blumenfeld, and Nickla is reversed. DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1–5, 7–11 103 First, Donovan, Gregori, Gross, Blumenfeld, Nickla 1–5, 7–11 Provisional Obviousness-type Double Patenting, ’491, 98412 Overall Outcome 1–5, 7–11 REVERSED 12 As explained above, we do not reach these rejections.