Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a national stage filing of PCT US2022/015567, filed 2/8/22, and claims benefit of priority to US 63/146,800, filed 2/8/21.
Response to Amendment/Status of the Claims
Applicant’s amendments to the claims filed 5/13/26 are acknowledged and have been entered. Claims 1 and 7 have been amended and claims 14-26 have been canceled. Claims 1-13 have been examined on the merits.
Applicant’s arguments filed 5/13/26 are acknowledged and have been considered. Any rejection and/or objection not specifically addressed below in original or modified form is herein withdrawn. Applicant argues that as amended the art does not teach or suggest the dosing regimen in amended claim 1. Applicant’s arguments have been considered; however, they are not persuasive. It is agreed that the limitation is not taught under anticipation, however the art relied on in the obviousness rejections, such as Kim, teaches that the effective dose is between 1ng/kg- 100mg/kg (e.g. claim 33) and that “A suitable or effective amount of bryostatin administered is determined by the attending physician depending on the patient, severity, and progression of the disease, and the aggressiveness of the treatment.” (page 20) and the compounds are administered for “a given period such as 1, 2, 3, 4, 5, 6, or 7 days.” (page 4). Loftsson provided additional teachings on tailoring dosing regimens to patients for a variety of factors. In combination, the art teaches optimization of the dosing regimens and the reasons for doing so, such that it is conventional, routine, and expected, that dosing is optimized for drug delivery to obtain the most efficacy. In contrast, the instant specification provides the instant regimens in, for example, paragraph [0004], however there is nothing that suggests this is anything beyond an optimization regimen, as would have been done by Kim along with the teachings of Loftsson. Accordingly, the claims are/remain rejected, as set forth below, modified to reflect the amendments to the claims. It is noted that all references relied upon have been cited in the previous office action.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-6, 12, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in view of LOFTSSON (Essential Pharmacokinetics. Chapter 5- Pharmacologic Response and Drug Dosage Adjustments. 2015, pages 119-130).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, specifically bryostatin-1 and to dosing regimens.
Kim teaches treating a patient suffering from a neuroinflammatory disorder with a bryostatin (claim 4), where the patient is suffering from optic neuritis, NMO, or NMOSD (claims 6 and 7), where the bryostatin is bryostatin-1 (claims 13 and 14) or a derivative (claim 15) -which would be a “bryolog” (instant spec [0036]). The bryostatin is administered orally, IV, IM, transdermally, parenterally, intrathecally, or a combination thereof, preferably orally (claim 32). Because so few members are recited in the claim, once could at once envisage each individually.
With regards to instant claim 2, Kim teaches treating optic nerve neuroinflammatory disorders of any origin/association, and thus nothing in Kim precludes practicing the method in patient where condition is associated with MS. Furthermore, Kim provides methods for treating MS in patients with bryostatins (e.g. claim 1), where the bryostatin provides an anti-inflammatory, immunosuppressive, neuromodulatory effect, or a combination thereof (claim 17), where the bryostatin reduces one or more symptoms of MS (e.g. claim 20), where the symptoms include vision loss, double vision or other visual dysfunction, pain, and other symptoms (e.g. claim 21). Further, Kim teaches that, “In some embodiments, the symptom is physical or mental symptom including, without limitation… pain and/or loss of vision due to optic neuritis…” (spanning pages 18-19), thus Kim contemplated the optic neuritis as inflammation associated with MS.
Kim additionally teaches that the effective dose is between 1ng/kg- 100mg/kg (e.g. claim 33) and that “A suitable or effective amount of bryostatin administered is determined by the attending physician depending on the patient, severity, and progression of the disease, and the aggressiveness of the treatment.” (page 20). Kim additionally, teaches the dose is 1-200 µg/m2 body surface area, preferably 10-120 µg/m2 (spanning pages 20-21). Kim teaches the compounds are administered for “a given period such as 1, 2, 3, 4, 5, 6, or 7 days.” (page 4)
LOFTSSON provides teachings on therapeutic drug monitoring, where drug doses are adjusted to maintain plasma concentrations within a targeted therapeutic window and “tailoring a dose regimen to an individual patient.” (page 120, 5.1). Loftsson provides additional teachings on adjustment of dosing based on kidney/liver function, age, gender, weight, clinical status, nutritional status, genetic variability and drug interactions. Thus, the teachings are that one would understand that dosing of a drug may need adjustment to achieve the desired benefit.
While Kim provides dosing and teachings that the dose/regimen is optimized by the physician, Kim does not specifically teach the regimens in claim 1. It would have been obvious, in light of the teachings of Kim and Loftsson teaching optimization of dosing regimens to achieve therapeutic results, to determine all optimum and operable conditions of the dosing regimens including the dose and timing, because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2145.05).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-7, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in view of LOFTSSON, as applied to claims 1-6, 12 and 13, above, and in further view of WENDER (The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin. J. Am. Chem. Soc. 2002, 124, 13648-13649), WENDER 2 (Total Synthesis and Initial Biological Evaluation of New B-Ring-Modified Bryostatin Analogs. Org. Lett. Oct. 2006 8(23) pages 5299-5302) and WENDER 3 (Role of the A-Ring of Bryostatin Analogues in PKC Binding: Synthesis and Initial Biological Evaluation of New A-Ring-Modified Bryologs. Org. Lett. March 2005 7(10) pages 1995-1998).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, where the activator is a bryostatin analog (bryology), specifically one of 5 analogs.
The teachings of Kim and Loftsson are presented above. Kim additionally teaches that the bryostatin analogs used can be any of those found in the literature, including the bryologs of Wender (Kim internally citing various citations including those recited above). It is noted that the instant specification admits that Analog 1 (first structure, instant claim 7) is from Wender (spec, para [0038]), and Analog 2 is found in Wender 2 (spec, para [0039]). Wender 3 teaches the R=t-butyl, phenyl and (CH2)3-p-Br-phenyl derivatives of instant claim 7 (e.g. Abstract).
While Kim does not explicitly claim use of the bryologs of instant claim 7, it would have been obvious to have used any bryolog in the method of treating optical nerve inflammation, including those of Wender, as Kim specifically instructs use of bryostatin analogs described in the references cited, specifically pointing to Wender 1, 2, and 3 (page 16). One would have immediately recognized the instruction to substitute one bryolog for another (or for bryostatin-1) in the method, as Kim teaches practicing the method with bryostatin-1 or a derivative (e.g. claim 13) and provides direct guidance on the sources of those analogs to choose.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over TASSOS (US 2019/0192466 A1) in view of ALKON (US 2014/0315990 A1), BALCER (Optic Neuritis. N Engl J Med 2006;354:1273-1280), and LOFTSSON (cited above).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, where the activator is a polyunsaturated fatty acid (PUFA), specifically a cyclopropanated derivative ester.
The teachings of Loftsson are above.
Tasos teaches the treatment, amelioration or prevention of optic nerve damage due to ... optic neuritis, comprising administering to a person a composition comprising between 3 g and 15 g of eicosapentaenoic acid and docosahexaenoic acid, in a mass ratio EPA:DHA from 1:1 to 5:1. Tasos additionally teaches that additional compounds used in the treatment are contemplated, including prodrugs (e.g. esters) and derivatives (para [0069]-[0076]). Tasos does not specifically teach the cyclopropanated form of the DHA ester.
Alkon teaches that cyclopropanated fatty acids exhibit low toxicity and are readily imported into the brain where they have a long half-life. Conversion of the double bonds to cyclopropane prevents oxidation and metabolism to inflammatory byproducts and has a more rigid structure that results in greater PKC activation, potentially more selective to PKC-ε (para [0081]). DHA-CP6 (instant claim 9 where R is methyl) has been shown to be effective at 10nM concentrations (citing US 2010/0022645). Alkon additionally teaches that the compounds are used for treating neurodegenerative disorders. Balcer is relied on for the beneficial teachings that optic neuritis is a neurodegenerative disorder (throughout).
It would have been obvious to have used the compounds, such as DHA-CP6 in the method of Tasos to take advantage of the low toxicity, lower effective dose concentrations, reduced inflammatory byproducts from metabolism, and the increased half-life. One would have been motivated to have used any derivative, including DHA-CP6, as Tasos tells you to use derivatives, and one would have looked to the art to find one with improved features- here, the improvement being that DHA-CP6 metabolism results in less inflammatory byproducts- something that would be of benefit in treating an inflammatory condition (optic neuritis).
With regards to the claimed dosing regimen, while Alkon provides dosing ranges, Alkon does not specifically teach the regimens in claim 1. It would have been obvious, in light of the teachings of Alkon and Loftsson teaching optimization of dosing regimens to achieve therapeutic results, to determine all optimum and operable conditions of the dosing regimens including the dose and timing, because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2145.05).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-7 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in view of LOFTSSON, as applied to claims 1-6, 12 and 13, above, and in further view of GUAN (US 2003/0027755 A1).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, where the activator is a growth factor, e.g. IGF.
The teachings of Kim and Loftsson are above.
While Kim teaches treating optic nerve inflammation such as optic neuritis, Kim does not teach using IGF-1.
Guan teaches administration of IGF-1 to restore myelination of axons (e.g. claim 1, claims 10-14), where the neural injury or disease is selected from optic neuritis (claim 9). Because there are so few options, one could at once envisage each one individually.
It would have been simple substitution to replace the bryostatin of Kim with the IGF-1 of Guan, as they are both PKC activators, and used for the same purpose, and to gain the benefit of the restoration of myelination of axons. In making the substation, and relying on the teachings of Kim and Loftsson, it would have been obvious to have optimized the dosing regimen to achieve therapeutic results, to determine all optimum and operable conditions of the dosing regimens including the dose and timing, because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2145.05).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-7 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in view of LOFTSSON, as applied to claims 1-6, 12 and 13, above, and in further view of BARTKE (US 2003/0032589 A1).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, where the activator is a growth factor, e.g. IGF.
The teachings of Kim and Loftsson are above.
While Kim teaches treating optic nerve inflammation such as optic neuritis, Kim does not teach using NGF.
Bartke teaches treating optic nerve inflammation in a method for preventing further demyelination in a patient having an inflammatory disease of the optic nerve, comprising administering an effective amount of NGF or an active fragment of NGF (e.g. claim 14).
It would have been simple substitution to replace the bryostatin of Kim with the NGF of Bartke, as they are both PKC activators, and used for the same purpose, and the NGF of Bartke provides the improvement/benefit of preventing further demyelination. In making the substation, relying on the teachings of Kim and Loftsson, it would have been obvious to have optimized the dosing regimen to achieve therapeutic results, to determine all optimum and operable conditions of the dosing regimens including the dose and timing, because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2145.05).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-7 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in view of LOFTSSON, as applied to claims 1-6, 12 and 13, above, and in further view of CELA (WO 2010/118761 A1).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, where the activator is a growth factor, e.g. IGF.
The teachings of Kim and Loftsson are above.
While Kim teaches treating optic nerve inflammation such as optic neuritis, Kim does not teach using polyunsaturated fatty acid (PUFA).
Cela teaches administration of DHA (a PUFA) to a patient suffering from optic neuritis in the right eye where the visual acuity improved from 4/10 to 1/10 in the right eye (example 14.2, page 72).
It would have been simple substitution to replace the bryostatin of Kim with the DHA of Cela, as they are both PKC activators, and used for the same purpose, and the DHA of Cela provides the improvement/benefit of improving visual accuity. In making the substation, relying on the teachings of Kim and Loftsson, it would have been obvious to have optimized the dosing regimen to achieve therapeutic results, to determine all optimum and operable conditions of the dosing regimens including the dose and timing, because such conditions are art-recognized result-effective variables that are routinely determined and optimized in the art through routine experimentation. ("[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, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2145.05).
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Andrew D Kosar whose telephone number is (571)272-0913. The examiner can normally be reached Monday-Friday, 7am-3:30pm.
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/Andrew D Kosar/ Supervisory Patent Examiner, Art Unit 1625
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