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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/14/26 has been entered.
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 4/14/26 are acknowledged. Any objection or rejection from the 1/14/26 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and the species as set forth in the reply filed on 11/14/24 were elected.
The claims were previously amended to remove the elected species (see 6/13/25). Claim 1 currently encompasses the elected species. Claims to the elected species are rejected as set forth below. Any relevant art that was previously uncovered during the search (for example when the elected species was excluded from the claims – see 6/13/25) is included herein in order to advance prosecution.
Claims 9-13 have been canceled.
Claims 1-8 are being examined.
Priority
The priority information is found in the filing receipt dated 9/10/24.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is a ‘new matter’ rejection. Section 2163 of the MPEP states: ‘While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure’.
Claim 1 has been amended to add a wherein clause as the last 3 lines of the claim. The amendment recites ‘at least 0.05 mg/ml’, ‘human neuronal cell line model’ and ‘at least 30%’. All of the dependent claims incorporate such claim language.
With respect to range recitations, MPEP 2163.05 III recites “A corresponding new claim limitation to "at least 35%" did not meet the description requirement because the phrase "at least" had no upper limit and caused the claim to read literally on embodiments outside the "25% to 60%" range”. In the instant case ‘at least 0.05 mg/ml’ has no upper limit and ‘at least 30%’ has no upper limit. One would not recognize 0.05 mg/ml (as used in example 5) as support for at least 0.05 mg/ml. One would not recognize 32% and 33% (as recited in figure 5) as support for ‘at least 30%’. Further, MPEP 2163.05 I A recognizes that “omission of a limitation can raise an issue regarding whether the inventor had possession of a broader, more generic invention”. In the instant case, ‘human neuronal cell line model’ is broader than SH-SY5Y (as used in example 5).
As such, there is no reason to conclude that claims 1-8 are supported in the specification through express, implicit, or inherent disclosure for at least the reasons discussed above.
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) 1-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cameron et al. (‘Polyarginines are potent furin inhibitors’ The Journal of Biological Chemistry 2000 v275(47) 2000, pages 36741-36749; ‘Cameron’).
Cameron teach identifying inhibitors using positional scanning amidated and acetylated synthetic hexapeptide libraries (abstract). Cameron teach that an L-amino acid library consisted of 120 peptide mixtures with amino-terminal acetylation and carboxyl-terminal amidation (first paragraph of experimental procedures on page 36742). Cameron teach that for each position, 20 mixtures were surveyed each of which was defined by 1 of the 20 natural amino acids and the other undefined positions were any of the amino acids except cysteine (first paragraph of experimental procedures on page 36742). Cameron teach that the libraries and individual compounds were synthesized using peptide synthesis (first paragraph of experimental procedures on page 36742). In figure 2, Cameron shows peptides of formula Ac-6-XXXXX-NH2 (where the numbered amino acid corresponds to the furin cleavage position – P6P5P4P3P2P1).
In relation to the peptide of claim 1, Cameron teach that an L-amino acid library consisted of 120 peptide mixtures with amino-terminal acetylation and carboxyl-terminal amidation (first paragraph of experimental procedures on page 36742). Cameron teach that for each position, 20 mixtures were surveyed each of which was defined by 1 of the 20 natural amino acids and the other undefined positions were any of the amino acids except cysteine first paragraph of experimental procedures on page 36742). Thus, the library of Cameron includes the peptide Ac-Arg-Trp-Gln-Lys-Asn-Gln-NH2 which is instant SEQ ID NO:1 where R1 is acetyl and R2 is NH2.
In relation to the functional language of claims 1-6, as discussed above the prior art suggest Ac-Arg-Trp-Gln-Lys-Asn-Gln-NH2 which meets the claim limitations as discussed above and specifically comprises SEQ ID NO:1. The claim language ‘when present in a concentration.. in a human neuronal cell line’ is interpreted as a conditional limitation (compare MPEP 2111.04 II). Since the peptide comprises SEQ ID NO:1, it is interpreted as having the recited function.
In relation to claim 8, Cameron teach identifying inhibitors using positional scanning amidated and acetylated synthetic hexapeptide libraries (abstract) where the library is a composition.
Claim Rejections - 35 USC § 103
The rejections below are based on previously cited art and are updated based on the claim amendments.
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) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Takahashi et al. (WO 2021/167107 08-21) in view of Adessi et al. (‘Converting a peptide into a drug: strategies to improve stability and bioavailability’ Current Medicinal Chemistry v9 2002 pages 963-978; ‘Adessi’).
Takahashi et al. is not in the English language. The English language equivalent (US 2023/0203098; ‘Takahashi’) will be referenced herein.
Takahashi teach a peptide with the function of passing through the blood brain barrier which has the sequence AVFVWNYYIISC or a modified sequence thereof (abstract and claim 1). Takahashi recites specific sequences including SEQ ID NO:249 (claims 16-17) where SEQ ID NO:249 is AVFVWNYYIKRRYYC (page 197). Takahashi recognizes that the 14th position can be meTyr or Tyr (section 0272). Takahashi suggest administration of the peptides (sections 0028 and 0424). Takahashi recognizes that the polypeptides are easily metabolized and suggest modifications to increase the residence time in the blood (section 0417). Takahashi teach compositions of the peptides (section 0416).
Takahashi does not teach a specific example with a peptide as claimed with a C-terminal amide.
Adessi teach strategies to improve stability and bioavailability of peptides (title and abstract). Adessi specifically teach that C-terminal amidation is a strategy that has been widely used to improve stability (page 967 section ‘N- and C-termini modifications’). In Table 1 (pages 964-965), Adessi include a large number of examples of peptides which include a C-terminal amidation.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Takahashi based on the express teachings and suggestions of Takahashi. Takahashi recites specific peptides including SEQ ID NO:249 (claims 16-17) and teach specific functions of the peptide (abstract) thus one would have been motivated to use for such purpose. Takahashi recognizes that the 14th position can be meTyr or Tyr (section 0272) so one would have been motivated to make SEQ ID NO:249 of sequence AVFVWNYYIKRRYYC (page 197). Since Takahashi suggest administration of the peptides (sections 0028 and 0424) and recognizes that the polypeptides are easily metabolized and suggest modifications to increase the residence time in the blood (section 0417) one would have been motivated to modify the peptide as taught by Adessi. Since Adessi teach that C-terminal amidation is a strategy that has been widely used to improve stability (page 967 section ‘N- and C-termini modifications’) one would have been motivated to C-terminally amidate the peptide of Takahashi to result in AVFVWNYYIKRRYYC-NH2. One would have had a reasonable expectation of success since methods of synthesis were known (see section 0411 of Takahashi).
In relation to the peptide of claims 1 and 7, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 where AVFVWNYYI is R5-CO (where CO is present due to the amide bond) and R5 is substituted C6-C30 aryl due to the phenyl group of phenylalanine (F). The generic recitation of R5-CO and substituted C6-C30 aryl does not require a specific point of attachment of the substituted group. R2 is NH2 and KRRYYC corresponds to SEQ ID NO:2.
In relation to the functional language of claims 1-6, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 which meets the claim limitations as discussed above and specifically comprises SEQ ID NO:2. The claim language ‘when present in a concentration.. in a human neuronal cell line’ is interpreted as a conditional limitation (compare MPEP 2111.04 II). Since the peptide comprises SEQ ID NO:2, it is interpreted as having the recited function.
In relation to claim 8, Takahashi teach compositions of the peptides (section 0416).
Claim(s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over by Patel et al. (US 10,176,292; ‘Patel’).
Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536). Patel teach that figure 2A discloses KDRVY as SEQ ID NO:2 (column 7 lines 1-5). Example 1 states that figure 2A relates to a bound ligand (column 68).
Patel does not teach a specific example where SEQ ID NO:102 includes a C-terminal amide.
Patel teach that an amino acid may be modified by amidation to alter the circulating half life of the polypeptide (column 15 lines 19-30) and specifically recognizes terminal amidation (column 24 lines 28-32). Patel specifically recognizes methods of making modulators and polypeptides (abstract and 3rd paragraph of column 3). Patel teach that the protein of interest is a central player in the innate immune response (column 3 first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Patel based on the express teachings and suggestions of Patel. Patel teach that the protein of interest is a central player in the innate immune response (column 3 first paragraph). Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536). Patel teach that figure 2A discloses KDRVY as SEQ ID NO:2 (column 7 lines 1-5). Example 1 states that figure 2A relates to a bound ligand (column 68). Since Patel teach a specific peptide, one would have been motivated to make and use such peptide. Patel teach that an amino acid may be modified by amidation to alter the circulating half life of the polypeptide (column 15 lines 19-30) and specifically recognizes terminal amidation (column 24 lines 28-32). Thus, one would have been motivated to modify the KDRVY peptide as suggested by Patel to include a C-terminal amidation. One would have had a reasonable expectation of success since methods of synthesis were known.
In relation to the peptide of claims 1 and 7, Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536) and suggest amidation as discussed above. When the C-terminal end is amidated the peptide is such that R1 is H and R2 is NH2.
In relation to the functional language of claims 1-6, Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536) which is the same core sequence recited for the 4th sequence recited in claim 1. The claim language ‘when present in a concentration.. in a human neuronal cell line’ is interpreted as a conditional limitation (compare MPEP 2111.04 II). Since the peptide has the same primary sequence, it is interpreted as having the recited function. Further, the peptide with R1 is H and R2 is NH2 is the elected species.
In relation to claim 8, Example 1 states that figure 2A relates to a bound ligand (column 68) so the peptide was in a composition. Patel specifically teach compositions (column 47).
Response to Arguments - 103
Applicant's arguments filed 4/14/26 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue that Takahashi teach for blood-brain barrier penetration not sodium channel signaling, MPEP 2144 IV expressly recognizes that the reason to modify a reference can be for a different purpose. Since Takahashi suggest administration of the peptides (sections 0028 and 0424) and recognizes that the polypeptides are easily metabolized and suggest modifications to increase the residence time in the blood (section 0417) one would have been motivated to modify the peptide as taught by Adessi. Since Adessi teach that C-terminal amidation is a strategy that has been widely used to improve stability (page 967 section ‘N- and C-termini modifications’) one would have been motivated to C-terminally amidate the peptide of Takahashi to result in AVFVWNYYIKRRYYC-NH2.
Although applicants argue about the teachings of Adessi and Takahashi alone, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue that Adessi does not teach acquiring sodium channel inhibitory activity, the instant claims are not drawn to methods of acquiring inhibitory activity.
Although applicants argue about the use of hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Although applicants argue about decreasing sodium channel activity, the instant claims are not drawn to methods of decreasing sodium channel activity. In relation to the functional language of claims 1-6, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 which meets the claim limitations as discussed above and specifically comprises SEQ ID NO:2. The claim language ‘when present in a concentration.. in a human neuronal cell line’ is interpreted as a conditional limitation (compare MPEP 2111.04 II). Since the peptide comprises SEQ ID NO:2, it is interpreted as having the recited function.
Although applicants argue that with respect to the rejection based on Patel that the claims have been amended, the amended claims are addressed above.
Although applicants argue about confirming a reproducible and concentration dependent biological effect, the instant claims are not methods of confirming. In relation to the functional language of claims 1-6, Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536) which is the same core sequence recited for the 4th sequence recited in claim 1. The claim language ‘when present in a concentration.. in a human neuronal cell line’ is interpreted as a conditional limitation (compare MPEP 2111.04 II). Since the peptide has the same primary sequence, it is interpreted as having the recited function. Further, the peptide with R1 is H and R2 is NH2 is the elected species.
Although applicants argue that Patel is directed to structural unrelated peptides, the rejection based on Patel is a 103 rejection. Further, Patel teach SEQ ID NO:102 which corresponds to Lys-Asp-Arg-Val-Tyr (columns 535-536) which is the same core sequence as instant SEQ ID NO:4.
Although applicants argue that “KDRVY (Patel) bears no structural or motif-based correspondence to the claimed sequences”, instant SEQ ID NO:4 as recited in claim 1 is R1-KDRVY-R2. Thus, applicants assertion is unfounded.
Although applicants argue that Patel does not teach modifying to result in sodium channel inhibition, the instant claims are not drawn to methods of modifying to result in sodium channel inhibition.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
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