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 .
Election/Restrictions
Applicant's election with traverse of Group I (i.e., a peptide comprising SEQ ID NO: 1) in the reply filed on October 12, 2023, is acknowledged.
As stated in the Action mailed on December 7, 2023, the traversal is on the grounds that there is unity of invention as well as the compounds of claim 1 share a significant structural element. This is not found persuasive because the prior art applied does teach the compounds of the instant invention and there is no significant common structural element within the instant Markush of claim 1. Applicants state that WO2015/153402 does not teach the instant invention. However, this is incorrect as it is the inventors work and teaching of the Markush of the claims and the specification of the WO document does possess significant overlap with the Markush of instant claim 1.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of Species 1 (i.e., SEQ ID NO: 5 as a single and specific peptide) in the reply filed on October 12, 2023, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note that SEQ ID NOs: 5-6 are free of the prior art as there is no teaching or suggestion to arrive at the specific combination of amino acids at positions X1-X8.
Status of Claims
Claims 1-19 were originally filed on April 20, 2021.
The amendment received on April 20, 2021, amended claims 3-7, 9-10, and 12-19. The amendment received on May 6, 2024, canceled claim 14, 16, and 19; amended claims 1-3, 7, 9-10, 12-13, 15, and 17-18; and added new claims 20-23. The amendment received on November 25, 2024, canceled claims 13, 15, 17-18, and 20-21; amended claims 1-4, 7-12, and 22; and added new claims 24-29. The amendment received on January 17, 2025, amended claims 1-4, 7-12, and 22. The amendment received on May 1, 2025, amended claim 1. The amendment received on December 29, 2025, canceled claims 2, 4, and 24-29; amended claim 1.
Claims 1, 3, 5-12, and 22-23 are currently pending and claims 1-6 and 22-29 are under consideration as claims 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 12, 2023.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2019/065593 filed December 11, 2019, and claims priority under 119(e) to U.S. Provisional Application No. 62/778,411 filed on December 12, 2018.
Sequence Interpretation
For claim 1, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 1 with any N- and/or C-terminal additions up to where the total length of the peptide is 35 amino acids. However, it is noted that SEQ ID NO: 1 encompasses up to 3 residues that can be absent, i.e., X2 and X7 must be absent and X3 may or may not be absent. As such, the minimum number of total residues in the peptide is 8 residues.
For claims 3 and 22, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 5 or 6 with any N- and/or C-terminal additions.
Response to Arguments
Applicant’s arguments, see Response, filed 12/29/25, with respect to 112(d) rejection have been fully considered and are persuasive. The rejection of claims 4-5 as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends has been withdrawn.
Applicant’s arguments, see Response, filed 12/29/25, with respect to 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1, 4-6, and 24-29 as being anticipated by Cai et al. US Publication No. 2017/0210780 A1 published on July 27, 2017 (cited in the IDS received on 10/12/23) has been withdrawn.
Applicant’s arguments, see Response, filed 12/29/25, with respect to 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-2, 6, and 26 as being anticipated by EMBL Accession No. Q8KL38, 7 pages (2006) has been withdrawn.
New Rejections Necessitated by Amendment
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.
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 pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, 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).
Claims 1 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. US Publication No. 2017/0210780 A1 published on July 27, 2017 (cited in the IDS received on 10/12/23).
For claims 1 and 5, Cai et al. teaches peptide fragments comprising a core sequence represented by Formula 1B as follows:
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(See Cai, [0056]-[0057], [0128]; claim 3). As such, a peptide fragment comprising a core sequence of Formula 1B encompasses the sequence: C-[absent/AVLIPFMW]-[absent/DEGNQSTYC]-C-R-H-N-T-A-G. Thus, Cai’s peptide fragment encompasses the instant peptide where instant X1 is S or T (i.e., correlates to Cai’s X2 when Cai’s X1 is absent), instant X2 is absent, instant X3 is absent, instant X4 is R, instant X5 is H, instant X6 is N, instant X7 is absent, and instant X8 is Ala as recited in instant claim 1. Furthermore, Cai et al. teaches that the peptide fragments comprising a core sequence represented by Formula 1B can each be used in a method of stimulating, increasing, or enhancing nitric oxide production by endothelial cells; stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells; and/or treating, inhibiting, or reducing an injury to a tissue or organ having endothelial cells such as myocardial infarction or ischemia/reperfusion injury by stimulating, increasing, or enhancing nitric oxide production by endothelial cells and/or stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells (See Cai, [0010]). Thus, Cai suggests that each peptide fragment species of Formula 1B would be useful for the same purpose and exhibit the same properties.
Similarly, Cai’s peptide fragment comprising a core sequence of Formula 1B constitutes a peptide with a minimum length of 8 amino acids (i.e., when Cai’s X1 and X2 are absent), 9 amino acids (i.e., when Cai’s X1 or X2 are absent), or 10 amino acids (i.e., when Cai’s X1 and X2 are present). As such, Cai’s peptide fragments encompass a total length of 8-10 amino acids thereby constituting a peptide that is 8 amino acid residues long as recited in instant claim 5 (i.e., instant X2, X3 and X7 are absent).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to follow the teachings of Cai and utilize a peptide fragment comprising a core sequence of C-[absent/AVLIPFMW]-[absent/DEGNQSTYC]-C-R-H-N-T-A-G such that instant X1 is S or T, instant X2 is absent, instant X3 is absent, instant X4 is R, instant X5 is H, instant X6 is N, instant X7 is absent, and instant X8 is Ala in order to treat, inhibit, or reduce an injury to a tissue or organ having endothelial cells such as myocardial infarction or ischemia/reperfusion injury by stimulating, increasing, or enhancing nitric oxide production by endothelial cells and/or stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because peptide fragments comprising a core sequence of C-[absent/AVLIPFMW]-[absent/DEGNQSTYC]-C-R-H-N-T-A-G were known to be administered to a subject in order to treat, inhibit, or reduce an injury to a tissue or organ having endothelial cells such as myocardial infarction or ischemia/reperfusion injury by stimulating, increasing, or enhancing nitric oxide production by endothelial cells and/or stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells as taught by Cai et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the peptide fragment of Cai comprised the core sequence of C-[absent/AVLIPFMW]-[absent/DEGNQSTYC]-C-R-H-N-T-A-G, and therefore, utilizing a core sequence of C-S/T-C-R-H-N-T-A-G would support the treatment, inhibition, or reduction an injury to a tissue or organ having endothelial cells such as myocardial infarction or ischemia/reperfusion injury by stimulating, increasing, or enhancing nitric oxide production by endothelial cells and/or stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells by constituting simple substitution of one known element for another to obtain predictable results and/or Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
For claim 6, Cai et al. teaches compositions comprising one or more peptide fragments (See Cai, [0107], [0133]; claim 10). Additionally and/or alternatively, since the peptide of claim 1 is the only component required in the composition of claim 6, it would then follow that Cai’s disclosure of a peptide comprising a core sequence of Formula 1B also constitutes a composition comprising the peptide. Thus, the teachings of Cai et al. satisfies the claim limitations as recited in instant claim 6.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 12/29/25 have been fully considered but they are not persuasive for the following reasons.
Applicant argues = Cai does not teach each and every element of claim 1 given that Cai’s peptides require a N-terminal Cys residue whereas the instant N-terminal residue is Ser or Thr (See Applicant’s Response received on 12/29/25, pg. 6). Pursuant to MPEP 2111.03(I), states that “[t]he transitional term “comprising”, which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Here, although amended claim 1 limits the length of the peptide to a range of 8 to 35 amino acids by utilizing the transitional phrase “consisting of”, claim 1 recites the transitional phrase “comprising” with respect to the peptide sequence of SEQ ID NO: 1. As described in the “Sequence Interpretation”, the scope of the claimed peptide encompasses any N- and/or C-terminal additions as long as the total length of the peptide is not more than 35 amino acids. As such, Cai’s N-terminal Cys residue is encompassed by the instantly claimed peptide sequence of SEQ ID NO: 1 even though not expressly recited. Therefore, contrary to Applicant’s argument, the inclusion of a N-terminal Cys residue in the peptide sequence does not exclude Cai’s peptide fragment sequence from rendering the instant peptide obvious.
Maintained/Modified Rejections in light of Applicants’ Amendments
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.
Claims 1 and 5-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 10-17 of U.S. Patent No. 10,550,163 B2 (cited in the IDS received on 5/6/24). Please note that the rejection has been updated in light of Applicants’ amendments. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘163 claims:
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(‘163, claims 1 and 30 corresponding to issued claims 1 and 2, respectively). ‘163 also claims where the peptide is about 8-30, etc. amino acid residues long (See ‘163, claims 4 and 6), or is 8-11 amino acid residues long (See ‘163 claims 5 and 7). ‘163 claims a composition comprising a first and second peptide where each are represented by the peptide of claim 1 (See ‘163, claim 10). Furthermore, ‘163 claims methods of using the peptide of claim 1 (See ‘163, claims 11-17). As discussed in the 103(a) rejection over Cai et al. (note: Cai et al. cited supra is the published application of ‘163), a peptide comprising a core sequence of Formula 1B renders obvious instant claims 1 and 5. Thus, the ‘163 claimed invention is not patentably distinct from the instantly claimed invention.
Claims 1 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-19 of copending Application No. 17/286,851 (Cai et al. US 2021/0371463 A1) (cited in the IDS received on 10/12/23). Please note that the rejection has been updated in light of Applicants’ amendments. Although the claims at issue are not identical, they are not patentably distinct from each other because
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(‘851 claim 1). As such, ‘851’s peptide encompasses a peptide sequence where X2 is absent, instant, X3 is present and S or T thereby corresponding to instant X1, instant X2 is absent, instant X3 is absent, X4 can be R thereby corresponding to instant X4, X5 can be His thereby corresponding to instant X5, X6 can be N thereby corresponding to instant X6, instant X7 is absent, and X8 can be A thereby corresponding to instant X8. ‘851 also claims where the peptide is about 8-60, etc. amino acid residues long (See ‘851, claim 4), or is 8-11 amino acid residues long (See ‘851 claim 5). ‘851 claims a composition comprising the peptide of claim 1 (See ‘851, claim 6). Furthermore, ‘851 claims methods of using the peptide of claim 1 (See ‘851, claims 7-19) including methods of stimulating, increasing or enhancing nitric oxide production by endothelial cells; stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells; and/or treating, inhibiting, or reducing an injury to a tissue or organ having endothelial cells such as myocardial infarction or ischemia/reperfusion injury by stimulating, increasing, or enhancing nitric oxide production by endothelial cells and/or stimulating or inducing phosphorylation of ERK1/2 and/or eNOS in endothelial cells. Thus, the ‘851 claim invention renders obvious instant claims 1 and 5 for the same rationale utilized in the 103 rejection supra given that the species of 851’s SEQ ID NO: 1 are useful for the same purpose and exhibit the same properties. Therefore, ‘851’s claim invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5-6 and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-16 of copending Application No. 17/614,949 (Cai et al. US 2022/0226434 A1) (cited in the IDS received on 10/12/23) (cited in the IDS received on 6/6/23). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘949 claims:
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(See ‘949 claims 1, 3, and 14). As such, ‘949’s peptide encompasses a peptide sequence where X1 is S or T thereby corresponding to instant X1, X2 can be absent thereby corresponding to instant X2, X3 can be D thereby corresponding to instant X3, X4 can be R thereby corresponding to instant X4, X5 can be H thereby corresponding to instant X5, X6 can be N thereby corresponding to instant X6, X7 can be absent thereby corresponding to instant X7, and X8 can be A thereby corresponding to instant X8. Moreover, ‘949’s SEQ ID NO: 5 comprises instant SEQ ID NO: 5. ‘949 also claims where the peptide is about 8-60, etc. amino acid residues long (See ‘949, claim 3). Furthermore, ‘949 claims 6-13 further limit the method of using the peptide (See ‘949, claims 6-13). Thus, the ‘949 claim invention anticipates instant claims 1, 3, 5-6 and 22-23. Therefore, ‘949’s claim invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 12/29/25 have been fully considered but they are not persuasive. It is noted that Applicants’ arguments regarding the obviousness-type double patenting rejections over the ‘163 patent and ‘851 pending application are similar to the arguments to the prior art rejection addressed supra. The “Response to Arguments” section supra is incorporated herewith. Additionally it is noted that Applicants did not provide a response for the obviousness-type double patenting rejection over the ‘949 pending application. Thus, the obviousness-type double patenting rejections are maintained.
Conclusion
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 THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654