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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/04/2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS), dated 08/19/2025, comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Status of the application
For reasons internal to the USPTO, this application has been reassigned. The present examiner regrets if this is inconvenience to applicant(s).
Examiner acknowledges applicants filed, on 01/03/2026, claim amendments and arguments.
In light of applicants claim amendments and arguments, previous 112(d) and 102 rejections are withdrawn. However, applicants’ arguments for the previous 103 rejection and nonstatutory double patenting rejections are found not persuasive. Accordingly, the previous rejections are maintained and updated/modified to address claim amendments.
In addition, for clarification purpose, the examiner would like to re-emphasize that previous elected group I (corresponds to claims 1-17 and 31-33) and elected species, viz., nerinetide as an active agent, are still maintained [see Restriction requirement and election of species in the non-final office action, mailed on 05/19/2025].
Since, the examination is limited to elected species in this office action, the pending 112(a) written description rejection is withdrawn at this time of prosecution. However, in case elected species is found allowable, search will be expanded and previous 112(a) written description may be reimposed.
So, in this office action, claims are examined on merits in light of elected species only, and non-elected subject matter is withdrawn.
Response to Arguments
Applicants main argument is that the cited Tymianski reference teaches away from rather than toward exclusion of human subjects in which a thrombolytic agent is administered less than 3 hours before or less than 10 minutes after administering the active agent that inhibits PSD-95 from a population of subjects receiving both PSD-95 and a thrombolytic agent.
Tymianski does not say that their method does not work for human subjects. It simply exemplified their method in rats. As explained in the modified 103 rejection, Tymianski provided enough guidance on a rat model, and it can be easily extrapolated to the human subjects. The reason is that in the drug discovery, first step is testing the drug in vitro, then in vivo and then in animal models, such as mouse or rat, monkey etc., before testing on humans in clinical trials, which is a common practice in the art. Therefore, this limitation is obvious over the teachings of Tymianski. Moreover, applicants failed to prove or at least failed to explain “why not the method of Tymianski cannot be extrapolated to human subjects?”
With regard to nonstatutory double patenting rejections, it appears that applicants failed to argue explicitly and so, it is not clear their remarks. The rejection over 17/800,883 is withdrawn, since this application is abandoned. However, at the time of allowance, rejections over the later filed applications will be withdrawn.
Claim Rejections - 35 USC § 103 [Maintained and modified]
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 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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-17 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Tymianski (EP 2723363 B1).
For claims 1-2:
Tymianski teaches a method for treating ischemic stroke, comprising administering a PSD-95 inhibitor to a subject having or at risk of ischemia, and performing reperfusion therapy [see 0002, 0007-0008, claims 1-4].
Tymianski teaches combinational therapy for ischemia, wherein the method comprising administering (i) Tat-NR2B9C (aka nerinetide) as an active agent that inhibits PSD-95 and cleavable by plasmin, and (ii) tPA, a thrombolytic agent; wherein the subjects include subjects administered with mechanical reperfusion.
Tymianski teaches that Tat-NR2B9c and tPA can be given at separate times to improve outcomes from stroke and with tPA initiated 15 minutes after the infusion of Tat-NR2B9c (see Example 4). Figure 11 further demonstrates that Tat-NR2B9c plus tPA is more effective than tPA alone when given either concurrently or when the Tat-NR2B9c dose precedes the tPA dose.
Tymianski also teaches that cleavage of Tat-NR2B9c by plasmin is expected to occur to a lesser extent in humans than rats because the dose of tPA (by weight) for activation of plasminogen is ten-fold less in humans than rats. Thus, these data provide evidence that in humans the contribution of tPA can combined with that of Tat-NR2B9c in reducing damaging effects of stroke or other ischemia to the CNS with greater effect than either agent alone.
Difference is that Tymianski does not exemplify their method on human subjects.
However, Tymianski provided enough guidance on a rat model, and it can be easily extrapolated to the human subjects. The reason is that in the drug discovery, first step is testing the drug in vitro, then in vivo and then in animal models, such as mouse or rat, monkey etc., before testing on humans in clinical trials, which is a common practice in the art. Therefore, this limitation is obvious over the teachings of Tymianski.
For claims 3-8:
Tymianski teaches that Tat-NR2B9c and tPA can be given at separate times to improve outcomes from stroke and also teaches that tPA is initiated 15 minutes after the infusion of Tat-NR2B9c (see Example 4).
Above teachings reads applicants claimed limitations, since it requires more than 10 min (15 min) in the teachings of art.
For claim 9:
Tymianski teaches that a PSD-95 inhibitor for use in treating a damaging effect of ischemia on the central nervous system in a human subject having or at risk of ischemia wherein reperfusion therapy is performed on the subject [see claim 1].
For claims 10-11:
Tymianski teaches that a PSD-95 inhibitor for use in treating a damaging effect of ischemia on the central nervous system in a human subject having or at risk of ischemia wherein reperfusion therapy is performed on the subject [see claim 1].
Tymianski further teaches an agent for use in reperfusion therapy in a human subject also receiving an agent that inhibits PSD-95 binding to NMDAR 2B, 2A or nNOS wherein the reperfusion therapy and the agent treat a damaging effect of the ischemia on the central nervous system, wherein the agent is a thrombolytic, vasodilator or hypertensive agent, wherein the PSD-95 inhibitor is administered before reperfusion therapy is performed [see 0009, 0053-0054 and claim 10].
For claim 12:
Tymianski teaches that PSD-95 can be administered within a period of 0.5-24 hours after the onset of ischemia [see 0069]. If PSD-95 is administered after 3 hours, then according to teachings of Tymianski, at least 15 min interval is required to administer thrombolytic agent [see Example 4], and so, it should be after 3 hr 15 min, which falls claimed range.
For claim 13:
Tymianski teaches that the administration can be parenteral, intravenous, nasal, oral, subcutaneous, intra-arterial, intracranial, intrathecal, intraperitoneal, topical, intranasal or intramuscular [see 0077].
For claim 14:
Tymianski teaches population of 10 [see example 4] and it worked and therefore, it is expected to work for higher number or less number of population. Claimed method is based on specific molecular mechanism and it is independent of population. The group size is useful in statistical analysis, not for treating a condition.
For claim 15:
Tymianski teaches 4-5 min intravenous infusion 1 hour after stroke. However, duration of administration is optimizable parameter, since a skilled person in the art would determine duration of administration through a routine experimentation, so, this limitation is obvious, absent evidence to the contrary. Once active agent is administered, the administration of thrombolytic agent requires at least 15 min interval, as explained above under For claims 1-2.
For claim 16:
Tymianski teaches sequences of active agent and Tat, and it does not mentioned about D-amino acids, and so, the amino acids are interpreted as natural amino acids.
For claims 17 and 32-33:
See above For claims 1-2.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual limitations in the claimed method and their advantages in treating ischemic stroke, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
Nonstatutory Double Patenting Rejections
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.
(i) Claims 1-8, 10, 14-17, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 8-12, 23, 25 of US 10967041 (‘041).
The instant claims are directed to:
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The dependent claims are limited to specific population set(s), administration regimen, specific peptides, e.g. nerinetide and specific thrombolytic agent, tPA.
‘041 reference claims are directed to:
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The dependent claims are limited to administration regimen, ischemia type, specific agent, e.g. nerinetide (claim 8), subject has a stroke (claim 5), thrombolytic agent is tPA (claim 11), types of reperfusion, e.g. thrombolytic, mechanical (claims 9, 14), wherein the interval between administering PSD-95 and reperfusion therapy is 30 min to 6 hr (claim 12), reperfusion therapy administration time, e.g. more than 3 h or less than 24 h after onset of ischemia, select PSD-95 inhibitors, and subject is human (claim 25).
A person skilled in the art would have found it obvious to arrive at the claimed method(s) from the reference claims because they claim treating damaging effect of ischemia in subjects, for e.g. in cerebral ischemia with the active agent, PSD-95 inhibitor, e.g. Tat-NR2B9c which is nerinetide, administered in combination with reperfusion therapy (e.g. thrombolytic agent, e.g. tPA) at an interval between 30 min to 6 h. The subject population of the reference claims include subjects being treated with PSD-95 inhibitor administered at least 30 mins before thrombolytic agent. A person skilled in the art would have found it obvious to treat subjects with ischemic stroke to alleviate the damage caused by ischemia. Thus claims 1, 2, 17, 33 would have been obvious over the reference claims. The subject population in the reference claims do not include the population as in claims 3-8, 10. As to claim 14, it is within the skill of an artisan to treat 100 or more subjects as the reference claims teach treating damaging effects of ischemia with Tat-NR2B9C peptide (nerinetide) and with reperfusion therapy in ischemic stroke subjects. As to claim 15, the reference teaches that the active agent is administered at least 10 minutes before thrombolytic therapy. It is within the skill of an artisan to start the thrombolytic agent therapy after 20 mins from the start of active agent administration and the dosage regimen adjustment is routine. As to claim 16, it is within the skill of an artisan to use the peptide with all L-amino acids or all D-amino acids or a mixture of D and L amino acids.
(ii) Claims 1-10, 14-17, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 11-16, 23, 24, 28 of US 10064910 (‘910).
The instantly claimed method(s) as discussed above.
‘910 reference claims are directed to:
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The dependent claims are limited to PSD-95 therapy before reperfusion (claim 2), wherein the primate has stroke (claim 6), PSD-95 inhibitor is a peptide, tat-NR2B9C (claims 11-12), reperfusion performed with thrombolytic agent (claim 13), interval between administering PSD-95 and reperfusion therapy is 30 min to 6 hr; the reperfusion therapy is mechanical reperfusion; wherein the reperfusion therapy is performed more than 4.5 hours and less than 24 hours after onset of ischemia; the subject present symptoms of stroke (clam 28).
A person skilled in the art would have found it obvious to arrive at the claimed method from the reference claims because they claim treating damaging effect of ischemia in subjects, for e.g. stroke with the active agent is PSD-95 inhibitor, e.g. Tat-NR2B9c (nerinetide), administered with reperfusion therapy (e.g. thrombolytic agent, e.g. tPA) at an interval between 30 min to 6 h. The subject population of the reference claims include subjects being treated with PSD-95 inhibitor administered at least 30 mins before thrombolytic agent. A person skilled in the art would have found it obvious to treat subjects with ischemic stroke to alleviate the damage caused by ischemia. Thus claims 1, 2, 17, 33 would have been obvious over the reference claims. The subject population in the reference claims do not include the population as in claims 3-8, 10. Claim 9 is addressed by the reference claim teaching of mechanical reperfusion in the combination therapy without thrombolytic agent. As to claim 14, it is within the skill of an artisan to treat 100 or more subjects as the reference claims teach treating damaging effects of ischemia with Tat-NR2B9C peptide (nerinetide) and with reperfusion therapy in ischemic stroke subjects. As to claim 15, the reference teaches that the active agent is administered at least 10 minutes before thrombolytic therapy. It is within the skill of an artisan to start the thrombolytic agent therapy after 20 mins from the start of active agent administration and the dosage regimen adjustment is routine. As to claim 16, it is within the skill of an artisan to use the peptide with all L-amino acids or all D-amino acids or a mixture of D and L amino acids.
(iii) Claims 1-10, 14-17, 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US 11878044 (‘044).
The instantly claimed method(s) as discussed above.
‘044 reference claims are directed to method of treating stroke, comprising administering a PSD-95 inhibitor comprising a peptide comprising SEQ ID NO:38 or SEQ ID NO:68 at its C-terminus, the peptide being linked to an internalization peptide to a human subject having or at risk of stroke, and performing reperfusion therapy on the subject, wherein the PSD-95 inhibitor and reperfusion therapy synergistically treat the stroke. Claim 18 is directed to method of treating a subject population of humans subjects presenting sign(s) and/or symptom(s) of stroke, comprising administering a PSD-95 inhibitor comprising a peptide comprising SEQ ID NO:38 or SEQ ID NO:68 at its C-terminus, with or without reperfusion therapy. The dependent claims are limited to PSD-95 inhibitor is administered before reperfusion therapy is performed; PSD-95-inhibitor is Tat-NR2B9c (SEQ ID NO:6); reperfusion is performed by administering a plasminogen activator; plasminogen activator is tPA; wherein the interval between administering PSD-95 and reperfusion therapy is 30 min to 6 hr; the reperfusion therapy is mechanical reperfusion; reperfusion therapy administration regimen.
A person skilled in the art would have found it obvious to arrive at the claimed method from the reference claims because they claim treating stroke with the active agent is PSD-95 inhibitor, e.g. Tat-NR2B9c (nerinetide), administered with reperfusion therapy (e.g. thrombolytic agent, e.g. tPA) at an interval between 30 min to 6 h. Ischemic stroke is a type of stroke and hence it would have been obvious to treat ischemic stroke with a PSD-95 inhibitor agent. The subject population of the reference claims include subjects being treated with PSD-95 inhibitor administered at least 30 mins before thrombolytic agent. A person skilled in the art would have found it obvious to treat subjects with ischemic stroke to alleviate the damage caused by ischemia. Thus claims 1, 2, 17, 33 would have been obvious over the reference claims. The subject population in the reference claims do not include the population as in claims 3-8, 10. Claim 9 is addressed by the reference claim teaching of mechanical reperfusion in the combination therapy without thrombolytic agent. As to claim 14, it is within the skill of an artisan to treat 100 or more subjects as the reference claims teach treating damaging effects of ischemic stroke with Tat-NR2B9C peptide (nerinetide) and with reperfusion therapy in ischemia subjects. As to claim 15, the reference teaches that the active agent is administered at least 10 minutes before thrombolytic therapy. It is within the skill of an artisan to start the thrombolytic agent therapy after 20 mins from the start of active agent administration and the dosage regimen adjustment is routine. As to claim 16, it is within the skill of an artisan to use the peptide with all L-amino acids or all D-amino acids or a mixture of D and L amino acids.
(iv) Claims 1-10, 12, 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 62, 1 of 18/271407 (‘407) or claims 23, 32, 33 of 17791711 (‘711) in view of Tymianski (EP 2723363)
The instantly claimed method(s) as discussed above.
‘407 reference claims are directed to:
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‘711 reference claims are directed to:
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Claim 1 is an to active agent comprising an internalization peptide linked to an inhibitor peptide, which inhibits PSD-95 binding to NOS and/or NMDAR2B. Claim 21 is to A co-formulation comprising the active agent of any preceding claim 1 and a thrombolytic agent.
The reference claims do not teach nerinetide as the PSD-95 inhibitor active agent or the specific set of subpopulation of the subjects to be treated for ischemia.
Tymianski teachings discussed as above.
From Tymianski a person skilled in the art would have found it obvious to treat subjects with ischemia with PSD-95 inhibitor active agent, nerinetide to the specific subset of population, wherein subjects are administered PSD-95 inhibitor at least 10 minutes before the thrombolytic agent, e.g. tPA is administered. The subject population of Tymianski do not include the subjects as claimed. A person skilled in the art would have found it obvious to treat ischemic stroke with PSD-95 inhibitor agent and reperfusion therapy in specific set of population as claimed from the reference claims and the prior art. Thus claims 1-8, 10, 12, 17, 33 would have been obvious over the combined reference claims and Tymianski. As to claim 9, from Tymianski a person skilled in the art would have added in combination therapy, mechanical reperfusion without a thrombolytic agent. As to claim 14, it is within the skill of an artisan to treat 100 or more subjects as Tymianski is explicit in teaching the benefits of Tat-NR2B9C peptide (nerinetide) therapy with reperfusion therapy in ischemic stroke subjects. As to claim 15, the reference teaches that the reperfusion therapy can be started after the active agent administration for e.g. can be between 15 minutes to 6h. It is within the skill of an artisan to start the thrombolytic agent therapy after 20 mins from the start of active agent administration and the dosage regimen adjustment is routine. As to claim 16, it is within the skill of an artisan to use the peptide with all L-amino acids or all D-amino acids or a mixture of D and L amino acids.
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 SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
Prosecution Insights