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 .
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 12/24/25 are acknowledged. Any objection or rejection from the 9/24/25 office action that is not addressed below is withdrawn based on the amendments.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). The most recent amendment has expanded the scope of claim 1 to once again encompass 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 § 103
The claims were previously amended to remove the elected species (see 6/13/25). The most recent amendment has expanded the scope of claim 1 to once again encompass 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.
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) 1-8 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 R1 which corresponds to substituted non-cyclic aliphatic (which comprises -C(CH(CH3)CH2CH3)C(O)- at the terminal end where the substituted groups include AVFVWNYY and 2 oxygens on the terminal carbonyl), 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. 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. 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 12/24/25 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue that claim 1 requires a six amino acid peptide optionally bearing a defined R1 and R2 (page 6 2nd paragraph of 12/24/25 reply), such statement is factually incorrect for numerous reasons. SEQ ID NO:3 and SEQ ID NO:4 can contain a 5 amino acid core. Further, R1 and R2 are not optional. In addition, due to the broad language such as ‘substituted or unsubstituted non-cyclic aliphatic’ the peptide is not limited as to the number, type or size of substitution. Claim 1 is much broader than asserted by the applicant as evidenced by the claim language itself.
Although applicants argue about the use of hindsight to extract KRRYYC, the rejection is not based on extracting KRRYYC. In relation to the peptide of claims 1 and 7, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 where AVFVWNYYI is R1 which corresponds to substituted non-cyclic aliphatic (which comprises -C(CH(CH3)CH2CH3)C(O)- at the terminal end where the substituted groups include AVFVWNYY and 2 oxygens on the terminal carbonyl), R2 is NH2 and KRRYYC corresponds to SEQ ID NO:2. Claim mapping is not extracting a fragment.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue about functional limitations, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 which meets the claim limitations as discussed above and specifically comprises SEQ ID NO:2. Since the peptide comprises SEQ ID NO:2, it is interpreted as having the recited function.
Although applicants argue about truncating to KRRYYC, the rejection is not based on truncating to KRRYYC. In relation to the peptide of claims 1 and 7, as discussed above the prior art suggest AVFVWNYYIKRRYYC-NH2 where AVFVWNYYI is R1 which corresponds to substituted non-cyclic aliphatic (which comprises -C(CH(CH3)CH2CH3)C(O)- at the terminal end where the substituted groups include AVFVWNYY and 2 oxygens on the terminal carbonyl), R2 is NH2 and KRRYYC corresponds to SEQ ID NO:2. Claim mapping is not extracting a fragment.
Although applicants argue about a lack of motivation, 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 that Patel does not anticipate the claims, the instant rejection is a 103 rejection.
Although applicants argue about functional limitations, 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. 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. As discussed in detail above, the prior art suggest the elected species. Since a chemical and its properties are inseparable (see MPEP 2112.01 II) the peptide would have the recited function.
Although applicants argue about a lack of motivation, 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.
Although applicants argue that Patel does not provide guidance on the location of the terminal amidation and Patel provides a general disclosure that is well known not a suggestion, Patel specifically recognizes terminal amidation (column 24 lines 28-32). Since there are 2 terminal ends (N-terminus and C-terminus) there a finite number of terminal ends.
Although applicants argue that the sequence of Patel is not explained in detail, 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). Thus, Patel provides specifics about the peptide.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue about a lack of reasonable expectation of success, one would have had a reasonable expectation of success since methods of synthesis were known. The instant claims are product claims not methods of treating.
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 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