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 .
Status of the Claims
Claims 1-26, as amended on 8/21/23, have been examined on the merits.
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.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/21/23, 12/13/24, and 10/30/25 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that numerous citations are found through the specification and are not provided on any IDS submission, e.g. paragraph [0038] citations. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The three bromolog structures drawn in the claim are grainy and it is unclear what alkyl chain length is on the ester and other features of the compound. Because of this, the claim is indefinite. In looking to the specification, it is noted that more clear structures exist in paragraph [0038], though it is noted that the hydroxyl drawn after ring A (or between ring position 9 and ring C) drawn ‘in to’ the page could be improved to show more of the dashed bond, eliminating any ambiguity to the attachment point.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6, 12, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KIM (WO 2020/118282 A1, IDS 8/21/23).
The instant claims are drawn generally to treating optic nerve inflammation, via administration of a PKC activator, specifically bryostatin-1.
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.
Claim(s) 1, 2, 10 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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.
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.
Claim(s) 1, 10 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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. 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).
Claim(s) 1 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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 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).
Claim(s) 1 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by TASSOS (US 2019/0192466 A1).
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).
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-6, and 12-26 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23), above, 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.
The teachings of KIM are presented above. 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 the claims 14-26. 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 are rejected under 35 U.S.C. 103 as being unpatentable over KIM (WO 2020/118282 A1, IDS 8/21/23) in 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 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) and BALCER (Optic Neuritis. N Engl J Med 2006;354:1273-1280).
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 Tassos are above. 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).
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.
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/Andrew D Kosar/ Supervisory Patent Examiner, Art Unit 1625