2021000918 (P.T.A.B. May. 21, 2021)

Gary Borodic

Patent Trials and Appeals BoardMay 21, 2021

2021000918 (P.T.A.B. May. 21, 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. 15/834,491 12/07/2017 Gary E. Borodic Borodic 16.01 2984 26812 7590 05/21/2021 HAYES SOLOWAY P.C. 175 CANAL STREET MANCHESTER, NH 03101 EXAMINER FONTAINHAS, AURORA M ART UNIT PAPER NUMBER 1649 NOTIFICATION DATE DELIVERY MODE 05/21/2021 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 2021-000918 Application 15/834,491 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, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, and 38 as obvious (Appeal Br. 5).3 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 July 15, 2020, Appeal Brief (Appeal Br.) 3). 2 This Appeal is related to pending Appeal 2020-006237 (Application 16/013,552). 3 Claims 5, 7–10, 14, 15, and 18–25 stand withdrawn from consideration (see Examiner’s September 18, 2020, Answer (Ans.)). Appeal 2021-000918 Application 15/834,491 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.4 1:19–20). Appellant’s independent claims 1 and 32 are reproduced below: 1. A method of treating age-related macular degeneration, the method comprising: administering a botulinum neurotoxin, wherein the botulinum neurotoxin is botulinum toxin type A, to a human or mammalian patient suffering from or at risk for macular degeneration, wherein the botulinum neurotoxin is injected into the patient in an area other than an intra-ocular region or a subconjunctival region, wherein the botulinum neurotoxin is injected into or near the para-orbital region of the patient; and administering an anti-VEGF agent to the patient, wherein the anti-VEGF agent is bevacizumab wherein administering the botulinum neurotoxin increases potency or duration of action of the anti-VEGF agent, and wherein the administration of the botulinum neurotoxin mitigates wet and exudative macular degeneration. (Appeal Br. 22.) 32. A method of treating age-related macular degeneration, the method comprising: administering an anti-VEGF agent to a human or mammalian patient suffering from or at risk for macular degeneration, wherein the anti-VEGF agent is selected from the group consisting of: bevacizumab and aflibercept; and administering a botulinum neurotoxin to the patient, wherein the botulinum neurotoxin is botulinum toxin type A and the botulinum neurotoxin is injected into in a peri-orbital or a paraorbital region of the patient, 4 Appellant’s June 15, 2018, Specification. Appeal 2021-000918 Application 15/834,491 3 wherein administering the botulinum neurotoxin to the patient avoids diplopia, wherein the botulinum neurotoxin is administered in a dose that conforms with conventional dosing, and wherein administering the botulinum neurotoxin increases potency or duration of action of the anti-VEGF agent. (Id. at 26.) Appellant’s claims 4, 6, 11, 13, 16, 17, 26–28, 30 and 31 depend directly or indirectly from Appellant’s independent claim 1 (see Appeal Br. 22–26). Appellant’s claims 34, 35, 37, and 38 depend directly or indirectly from Appellant’s independent claim 32. Appeal 2021-000918 Application 15/834,491 4 Ground of rejection before this Panel for review:5 Claims 1, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, and 38 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of First,6 Gross,7 Blumenfeld,8 CATT, and Ma.9 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? 5 Appellant does not contest the provisional rejections of claims 1, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, and 38 under the judicially created doctrine of obviousness-type double patenting as being unpatentable over (a) claims 1–11 of copending Application No. 16/013,552 (’552) in view of The CATT Research Group, Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration, 364 THE NEW ENGLAND JOURNAL OF MEDICINE 1897–1908 (2011) (CATT) and (b) claims 1–16 of copending Application No. 16/015,984 (’984) in view of CATT (see Ans. 9 (Examiner finds that “the nonstatutory double patenting rejections of record . . . are not part of the Appeal Brief”); see also Appellant’s November 18, 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). 6 First, US 7,465,458 B2, issued Dec. 16, 2008. 7 Gross et al., US 7,146,209 B2, issued Dec. 5, 2006. 8 Blumenfeld, US 8,846,622 B2, issued Sept. 30, 2014. 9 Ma et al., Combination of antiangiogenesis with chemotherapy for more effective cancer treatment, 7 Mol. Cancer Ther. 3670–84 (2008). Appeal 2021-000918 Application 15/834,491 5 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. 4). 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. 4.) 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 embodiments, the Clostridial toxin may be a botulinum toxin Appeal 2021-000918 Application 15/834,491 6 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. 4–5.) 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). 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). 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 specific area of administration or administering an anti-VEGF agent as required in” Appellant’s claimed invention (Ans. 5). Appeal 2021-000918 Application 15/834,491 7 FF 8. Gross “relates to the use of electrical, chemical, mechanical and/or odorant stimulation for treating eye pathologies” (Gross 1:44–47; see generally Ans. 5). FF 9. 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 generally Ans. 5.) FF 10. Examiner finds that “Gross fails to treat the treatment of botulinum neurotoxin for macular degeneration or an anti-VEGF agent” (Ans. 5). FF 11. 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 Appeal 2021-000918 Application 15/834,491 8 id. at 5:22–55; id. at 5:36–37 (Blumenfeld discloses the use of botulinum toxin type A); Ans. 5). FF 12. Blumenfeld discloses that “direct sphenopalatine administration of presynaptic neurotoxins can be used” (Blumenfeld 11:30–31; see Ans. 5). FF 13. Examiner finds that “Blumenfeld does not teach treating macular degeneration” (Ans. 5). FF 14. Examiner finds that CATT discloses the treatment of “macular degeneration with bevacizumab (Avastin®) and ranibizumab . . . which are anti-VEGF agents,” wherein “both treatments improved visual acuity and reduced the amount of fluid in or under the retina in AMD patients” (Ans. 6 (citing CATT, Abstract, 1898: col. 1, paragraph 1; 1902: col. 2; 1907: Discussion)). FF 15. Examiner finds that “CATT does not teach treating macular degeneration with botulinum neurotoxin” (Ans. 6). FF 16. Examiner finds that Ma discloses “the combined use of anti-VEGF agents, such as ranizumab and bevacizumab . . ., with botulinum toxin to improve the penetrance of different treatments” (Ans. 6 (citing Ma 3671: Table 1; 3672: Table 2; 3678: col. 1, paragraph 3)). FF 17. Examiner finds that Ma teaches that in theory one would not want to increase the permeability of the blood vessels in the regular treatment because it assists in tumor growth; however, the long term effects of increasing the permeability of the anti-tumor drugs to be able to penetrate tumor tissues outweigh any potential detrimental earlier effects (Ans. 6–7). FF 18. Examiner finds that “Ma does not teach treating wet macular degeneration” (Ans. 7). Appeal 2021-000918 Application 15/834,491 9 ANALYSIS Based on the combination of First, Gross, and Blumenfeld, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious to treat “macular degeneration by injection of botulinum neurotoxin through a needle to the zygomatic arch where the SPG is found” and that, “[b]y injecting the treatment of botulinum neurotoxin in the SPG, it avoids the eye and the subconjunctival region of the eye and therefore, avoids the complications associated with injecting botulin neurotoxin into those areas” (Ans. 6 (citing Blumenfeld 12:35–45)). Examiner finds, however, that the combination of First, Gross, and Blumenfeld fails to “teach administering botulinum neurotoxin in combination with an anti-VEGF agent to treat macular degeneration” and relies on CATT and Ma to make up for this deficiency in the combination of First, Gross, and Blumenfeld (Ans. 6). Based on the combination of First, Gross, Blumenfeld, CATT and Ma Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious to treat macular degeneration with a combination of an anti-VEGF agent, such as bevacizumab or ranibizumab, with botulinum neurotoxin (Ans. 7). Examiner reasons: [T]he combination of treatments will necessarily produce the same results as the instantly claimed method given that one is practicing the same active steps and administering the same treatments to the same patient population. MPEP 2145(11) states: “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)[] (“The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to Appeal 2021-000918 Application 15/834,491 10 an otherwise unpatentable invention.”). The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references. (Ans. 7–8; see also id. at 8–9) We are not persuaded. Appellant’s independent claim 1, reproduced above, requires, inter alia, the injection of botulinum toxin type A into or near the para-orbital region of a patient, other than an intra-ocular region or a subconjunctival region (see Appeal Br. 22). Appellant’s independent claim 32, reproduced above, requires, inter alia, the injection of botulinum toxin type A into a peri-orbital or a para-orbital region of the patient (see id. at 26). We find that First’s disclosure of locally administering botulinum toxin to the cornea of a patient’s eye, or topically administering botulinum toxin to a patient’s eye, (see FF 1–3) falls outside the scope of an injection into or near the para- orbital region of a patient, other than an intra-ocular region or a subconjunctival region (Appellant’s claim 1) or into a peri-orbital or a para- orbital region of the patient (Appellant’s claim 32) as required by Appellant’s claimed invention. Examiner failed to establish that First, Gross, Blumenfeld, CATT, and Ma alone, or in combination, teach or suggest the administration of botulinum neurotoxin into or near the para-orbital region of a patient or into a peri-orbital or a para-orbital region of the patient (see FF 1–18). The evidence of record does, however, support a finding 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” (FF 5). As Appellant explains, the locus of injection, Appeal 2021-000918 Application 15/834,491 11 according to their claim 1, “the paraorbital ganglion[,] contains cholinergic nerves with receptors that mediate endocytosis” (Reply Br. 6, n. 13). 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 peri-orbital 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 macular degeneration in a patient, as required by Appellant’s claims 1 and 32. 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. 6, n. 13).10 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 wAMD. . . . However, axoplasmic transport of botulinum toxin to the inner eye was simply not known prior to the time of invention and therefore this hindsight knowledge cannot be 10 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. 13), 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 claims 1 and 32, which results in little if any retrograde transport. Appeal 2021-000918 Application 15/834,491 12 used to bolster the obviousness rationale proposed by the Examiner. (Reply Br. 7; see also id. (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 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, Gross, Blumenfeld, CATT, and Ma (see e.g., Ans. 8). 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 Appeal 2021-000918 Application 15/834,491 13 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, Gross, Blumenfeld, CATT, and Ma 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 following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious” (see Ans. 12 (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 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, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, and 38 under 35 U.S.C. § 103(a) as unpatentable over the combination of First, Gross, Blumenfeld, CATT, and Ma is reversed. Appeal 2021-000918 Application 15/834,491 14 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 4, 6, 11, 13, 16, 17, 26–28, 30– 32, 34, 35, 37, 38 103 First, Gross, Blumenfeld, CATT, Ma 1, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, 38 1, 4, 6, 11, 13, 16, 17, 26–28, 30– 32, 34, 35, 37, 38 Provisional Obviousness-type Double Patenting11 Overall Outcome 1, 4, 6, 11, 13, 16, 17, 26–28, 30–32, 34, 35, 37, 38 REVERSED 11 As explained above, we do not reach these rejections.