DETAILED ACTION
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 .
Claim of Foreign Priority
There is no claim to foreign priority.
Election/Restrictions
Applicant’s election without traverse of bryostatin-1 in the reply filed on May 15, 2026, is acknowledged. Claims 1-6, 13-32, and 39 are readable on the elected species.
Status of the Claims
Claims 1-39 are pending. Claims 7-12 and 33-38 are withdrawn. Claims 1-6, 13-32, and 39 are examined.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-6, 13-24 and 28 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Alkon et al., (US2018/0311209).
Alkon teaches treating multiple sclerosis by administering bryostatin-1. See prior art claims 1, 3, 6, and 7. Dosing includes administering the PKC activator once a week for three consecutive weeks. Administration includes oral and intravenous routes. See par. 33. Dosing regiments includes about 0.1 to 100 mg/m2 at least about 10-40 ug/m2. See par.’s 41, 55, and 56. In some embodiments, the administration can continue in alternating intervals. See par. 38. Claim 15 is directed to administration at a dosage of 25 ug/m2. This is a dose used in examples and shown to be efficacious. Dosing shown in Table 1 includes administration in alternating weeks, once per week for 3 weeks and followed by 3 weeks off. A second round of dosing can be administered. See Tables 1 and 2. Dosing was also started at 10 ug/m2, 15 ug/m2, and 25 ug/m2. See Tables 6 and 7. Injections were tested once per week, once every other week, and 3 weeks on and 3 weeks off regimens. See Table 1.
Claims 1, 3-6, 13-24 and 28 are anticipated by the prior art.
Claims 1-6, 13, 14, 28-32, and 39 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kim et al., (US2022/0023255).
Kim teaches treating multiple sclerosis by administering a bryostatin, including bryostatin-1. See prior art claims 1, 13 and 14. Further, the MS can be RRMS, secondary progressive MD, progressive relapsing MS or others. See prior art claim 16. Administration can be oral or intravenous. See par.’s 82 and 83. A suitable dose includes 10 to 120 ug/m2. See oar, 80. Treatment can include MS symptoms in a symptomatic subject as well as preventing the onset of MS symptoms in a patient having MS or predisposed to MS. See Abstract. Treatment is able to work even when initiated at a late stage of the disease when peak adaptive immunity has subsided. Multiple stages of MS are treatable across various spectrums of severity. See par. 35. This is interpreted to include advanced MS. Bryostatins were shown to have an ability to remyelinate neurons. See par. 70. Kim also indicates that Bryostatin-1 is potent and even low doses administered only 3 days per week broadly decreased inflammation in the CNS and periphery. See par. 122. Doses as low as 10nM had direct and potent effects.
Claims 1-6, 13, 14, 28-32, and 39 are anticipated by the prior art.
Claim Rejections - 35 USC § 103
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.
Claims 1-6, 13-32, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al., (US2022/0023255), in view of Alkon et al., (US2018/0311209).
Kim teaches treating multiple sclerosis by administering a bryostatin, including bryostatin-1. See prior art claims 1, 13 and 14. Further, the MS can be RRMS, secondary progressive MD, progressive relapsing MS or others. See prior art claim 16. Administration can be oral or intravenous. See par.’s 82 and 83. A suitable dose includes 10 to 120 ug/m2. See oar, 80. Treatment can include MS symptoms in a symptomatic subject as well as preventing the onset of MS symptoms in a patient having MS or predisposed to MS. See Abstract. Treatment is able to work even when initiated at a late stage of the disease when peak adaptive immunity has subsided. Multiple stages of MS are treatable across various spectrums of severity. See par. 35. This is interpreted to include advanced MS. Bryostatins were shown to have an ability to remyelinate neurons. See par. 70. Kim also indicates that Bryostatin-1 is potent and even low doses administered only 3 days per week broadly decreased inflammation in the CNS and periphery. See par. 122. Doses as low as 10nM had direct and potent effects.
Kim does not teach an identical dosage regimen.
Alkon teaches treating multiple sclerosis by administering bryostatin-1. See prior art claims 1, 3, 6, and 7. Dosing includes administering the PKC activator once a week for three consecutive weeks. Administration includes oral and intravenous routes. See par. 33. Dosing regiments includes about 0.1 to 100 mg/m2 at least about 10-40 ug/m2. See par.’s 41, 55, and 56. In some embodiments, the administration can continue in alternating intervals. See par. 38. Claim 15 is directed to administration at a dosage of 25 ug/m2. This is a dose used in examples and shown to be efficacious. Dosing shown in Table 1 includes administration in alternating weeks, once per week for 3 weeks and followed by 3 weeks off. A second round of dosing can be administered. See Tables 1 and 2. Dosing was also started at 10 ug/m2, 15 ug/m2, and 25 ug/m2. See Tables 6 and 7. Injections were tested once per week, once every other week, and 3 weeks on and 3 weeks off regimens. See Table 1.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention in view of Alkon and Kim. One would be motivated to do so because the claimed agent is taught to be administered through oral and intravenous means to treat MS, including each type and severity of MS. Further, dosages for administration include those dosages claimed and also include weekly administrations for multiple cycles and administration multiple times weekly. Moreover, the potency of bryostatin-1 is recognized and is optimizable.
Claims 1-6, 13-32, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al., (US2022/0023255), in view of Alkon et al., (US2018/0311209), and in view of Alkon et al., (US2019/0350898) (“Alkon2”).
Kim teaches treating multiple sclerosis by administering a bryostatin, including bryostatin-1. See prior art claims 1, 13 and 14. Further, the MS can be RRMS, secondary progressive MD, progressive relapsing MS or others. See prior art claim 16. Administration can be oral or intravenous. See par.’s 82 and 83. A suitable dose includes 10 to 120 ug/m2. See oar, 80. Treatment can include MS symptoms in a symptomatic subject as well as preventing the onset of MS symptoms in a patient having MS or predisposed to MS. See Abstract. Treatment is able to work even when initiated at a late stage of the disease when peak adaptive immunity has subsided. Multiple stages of MS are treatable across various spectrums of severity. See par. 35. This is interpreted to include advanced MS. Bryostatins were shown to have an ability to remyelinate neurons. See par. 70. Kim also indicates that Bryostatin-1 is potent and even low doses administered only 3 days per week broadly decreased inflammation in the CNS and periphery. See par. 122. Doses as low as 10nM had direct and potent effects.
Kim does not teach an identical dosage regimen.
Alkon teaches treating multiple sclerosis by administering bryostatin-1. See prior art claims 1, 3, 6, and 7. Dosing includes administering the PKC activator once a week for three consecutive weeks. Administration includes oral and intravenous routes. See par. 33. Dosing regiments includes about 0.1 to 100 mg/m2 at least about 10-40 ug/m2. See par.’s 41, 55, and 56. In some embodiments, the administration can continue in alternating intervals. See par. 38. Claim 15 is directed to administration at a dosage of 25 ug/m2. This is a dose used in examples and shown to be efficacious. Dosing shown in Table 1 includes administration in alternating weeks, once per week for 3 weeks and followed by 3 weeks off. A second round of dosing can be administered. See Tables 1 and 2. Dosing was also started at 10 ug/m2, 15 ug/m2, and 25 ug/m2. See Tables 6 and 7. Injections were tested once per week, once every other week, and 3 weeks on and 3 weeks off regimens. See Table 1.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention in view of Alkon and Kim. One would be motivated to do so because the claimed agent is taught to be administered through oral and intravenous means to treat MS, including each type and severity of MS. Further, dosages for administration include those dosages claimed and also include weekly administrations for multiple cycles and administration multiple times weekly. Moreover, the potency of bryostatin-1 is recognized and is optimizable. Even further, Alkon2 teaches byrostatin doses were administered using 24 and 48 micrograms doses during first two weeks of protocols for 20 and 40 micrograms. These loading doses were thought to be beneficial. Loading doses were further discussed as being 20% higher than the assigned dose and administered one week apart. As such, a person of ordinary skill in the art while optimizing a dosage of bryostatin-1 would consider a loading dose and it may include a loading dose that is 20% higher than a maintenance dose. As such, there is a reasonable and predictable expectation of success in arriving at the claimed regimen in view of the cited prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Non-Provisional:
Claims 1-6, 13-32, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,173,140. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘140 patent is directing to treating MS with bryostatin-1 through intravenous administration of a dosing regimen that includes weekly administration of 20-50 ug/m2. The same API, subject, and dosing is presently claimed.
Claims 1-6, 13-32, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,045,447, in view of Mirage News, “Repairing synapses to combat multiple sclerosis,” Science January 26, 2021, https://www.miragenews.com/repairing-synapses-to-combat-multiple-sclerosis/- date accessed May 26, 2026.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘447 patent is directing to treating MS with bryostatin-1 through intravenous administration of a dosing regimen that includes a loading dose of two doses followed by slightly lower doses of 20 mcg. The same API, subject, and dosing is presently claimed.
Provisional:
Claims 1-6, 13-32, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 12, and 13 of copending Application No. 18/547,252. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘252 application are directed to treating optic nerve inflammation. However, this is associated with multiple sclerosis as shown in dependent claim 2. As such, the claims of the ‘252 application are directed to administration of a similar dose of the same API to a subject with a symptom caused by MS.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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