DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/12/25 has been entered.
Election/Restrictions and Claim Status
Applicants amendments and arguments filed 9/12/25 are acknowledged. Any objection or rejection from the 3/14/25 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and SEQ ID NO:8 were elected.
Claims 23-24 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/6/23.
Claims 2-22, 25-52, 54-56 and 58-68 have been canceled.
Since SEQ ID NO:8 was elected, newly added claims 69-78 and 80-85 are drawn to a non-elected species. Specifically, the elected species is SEQ ID NO:8 not a substituted version as in claims 71-78 and 80-85. Further, SEQ ID NO:8 does not necessarily include the components as recited in claims 69-70.
Claims 69-78 and 80-85 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/6/23.
Claims 1, 53, 57 and 79 are being examined.
Priority
The priority information is found in the filing receipt dated 4/19/22.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/12/25 has been considered by the examiner.
Claim Rejections - 35 USC § 112
The rejections below are new rejections necessitated by amendment.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 53, 57 and 79 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 as amended recites ‘SEQ ID NO:8’. Dependent claim 57 recites that the N-terminus is acetylated. The sequence listing for SEQ ID NO:8 recites that position 1 is acetylated. As such, the claims and the sequence listing appear to provide contradictory information. It is unclear if claim 1 requires the N-terminus to be acetylated and it is unclear if claim 57 is a proper dependent claim. None of the dependent claims clarify the claim scope.
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, 57 and 79 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
(1) Scope of the invention/Partial structure/disclosure of drawings:
Claim 1 recites ‘2 or 3 amino acid substitutions’ and specifically recites ‘is a VPAC2 selective agonist’. Claims 57 and 79 incorporate such limitations.
When 3 positions are substituted to any of the 20 standard amino acids there are at least 203 (8000) different possible sequences. Further, the substitutions are not limited to the 20 standard amino acids and the substitutions encompass many different possible combinations of locations (i.e. positions 1, 2, and 3; 1, 2 and 31; 1, 10 and 20, etc.).
The specification recites numerous sequences (Table 2 page 135-136 of the 4/15/22 specification). First, it is not clear if Table 2 is actual data or prophetic since page 137 of the 4/15/22 specification refers to prophetic binding assays. Although the table is labeled VPAC2 selective analogs, such conclusion does not seem to be consistent with the data. Although the statistical significance is not reported, SEQ ID NO:1 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. SEQ ID NO:19 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. Without knowing the statistical significance it is unclear which of the other sequences are VPAC2 selective.
(2) Level of skill and knowledge in the art/predictability in the art:
The level of skill in the art is high.
The specification recites numerous sequences (Table 2 page 135-136 of the 4/15/22 specification). First, it is not clear if Table 2 is actual data or prophetic since page 137 of the 4/15/22 specification refers to prophetic binding assays. Although the table is labeled VPAC2 selective analogs, such conclusion does not seem to be consistent with the data. Although the statistical significance is not reported, SEQ ID NO:1 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. SEQ ID NO:19 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. Without knowing the statistical significance it is unclear which of the other sequences are VPAC2 selective.
Pearson W (‘An introduction to sequence similarity (“Homology”) searching’ Curr Protoc Bioinformatics June 2013 printed as pages 1-9; previously cited) teach that homologous sequences do not always share significant sequence similarity and there are thousands of homologous protein alignments that are not significant (page 2 2nd complete paragraph).
(3) Physical and/or chemical properties and (4) Functional characteristics:
Claim 1 recites ‘is a VPAC2 selective agonist’. Claims 57 and 79 incorporate such limitation.
Claim 1 recites ‘2, or 3 amino acid substitutions’. Claims 57 and 79 incorporate such limitation.
When 3 positions are substituted to any of the 20 standard amino acids there are at least 203 (i.e. 8000) different possible sequences. Further, the substitutions are not limited to the 20 standard amino acids and the substitutions encompass many different possible combinations of locations (i.e. positions 1, 2, and 3; 1, 2 and 31; 1, 10 and 20, etc.).
The specification recites numerous sequences (Table 2 page 135-136 of the 4/15/22 specification). First, it is not clear if Table 2 is actual data or prophetic since page 137 of the 4/15/22 specification refers to prophetic binding assays. Although the table is labeled VPAC2 selective analogs, such conclusion does not seem to be consistent with the data. Although the statistical significance is not reported, SEQ ID NO:1 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. SEQ ID NO:19 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. Without knowing the statistical significance it is unclear which of the other sequences are VPAC2 selective.
If sequences that are in a Table (see Table 2) that is alleged to be ‘VPAC2 selective’ but the data shows otherwise then it is would surely be unpredictable which 2 or 3 substitutions would result in VPAC2 selective compounds as claimed.
As discussed above there are many possible analogs but it is not evident which of those have the required activity. As recognized by Pearson cited above, many of the homologous sequences may not be significant.
There is no adequate specific disclosed correlation between structure and function particularly related to what sequences are adequate to result in VPAC2 selective agonists. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus and that there is a lack of the predictability in the art thus that the applicant was not in possession of the claimed genus.
(5) Method of making the claimed invention/actual reduction to practice:
The specification recites various sequences (see Table 1). However, the functional information related to such sequences is not adequately disclosed.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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, 53, 57 and 79 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 recite ‘2 or 3 amino acid substitutions’ and specifically recites ‘is a VPAC2 selective agonist’. Claims 57 and 79 incorporate such limitations. Claim 53 has been amended to recite specific configurations of the x and z residue.
Applicants do not appear to provide information about where support for the amendments can be found. Claim 1 does require ‘VPAC2 selective agonist’. The specification recites numerous sequences (Table 2 page 135-136 of the 4/15/22 specification). First, it is not clear if Table 2 is actual data or prophetic since page 137 of the 4/15/22 specification refers to prophetic binding assays. Although the table is labeled VPAC2 selective analogs, such conclusion does not seem to be consistent with the data. Although the statistical significance is not reported, SEQ ID NO:1 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. SEQ ID NO:19 would not seem to be VPAC2 selective since the EC50 is lower for VPAC1. Without knowing the statistical significance it is unclear which of the other sequences are VPAC2 selective. Although the specification uses the phrase ‘VPAC2 selective’ such phrase alone is not adequate support for 2 or 3 amino acid substitutions with such function.
With respect to claim 53, the phrase ‘3R, 4S’ could not be located in the instant specification.
The courts have stated (Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1326, 56 USPQ2d 1481, 1486 (Fed. Cir. 2000)) that with respect to In re Ruschig 379 F.2d 990, 154 USPQ 118 (CCPA 1967) that “Ruschig makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say “here is my invention”. In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure. In the instant case, the mere insertion of phrases found in the specification is not adequate support for the instant claims which require specific functionality.
As such, there is no reason to conclude that claims 1, 53, 57 and 79 are supported in the specification through express, implicit, or inherent disclosure for at least the reasons discussed above.
Double Patenting
Claims were previously rejected under double patenting. Since the claims have been amended, rejections have been updated as set forth below.
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, 57 and 79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,278,595 (595; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each.
595 recites a composition comprising SEQ ID NO:18 (claim 1).
In relation to the composition of the instant claims 1 and 79, 595 expressly recites a composition with a carrier (claim 1).
In relation to the sequence of claim 1, SEQ ID NO:18 of 595 comprises instant SEQ ID NO:8 with 3 substitutions (at positions 9, 10 and 16). Since the structural limitations are met, the functional limitations have been interpreted as being met.
In relation to claim 57, SEQ ID NO:18 of 595 is acetylated at the N-terminus (per the sequence listing).
Claims 1, 57 and 79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,543,255 (255; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each.
255 recites SEQ ID NO:17 (claim 1) and a composition with a carrier (claim 6).
In relation to the composition of the instant claims 1 and 79, 255 expressly recites a composition with a carrier (claim 5).
In relation to the sequence of claim 1, SEQ ID NO:17 of 255 comprises instant SEQ ID NO:8 with 3 substitutions (at positions 9, 10 and 17). Since the structural limitations are met, the functional limitations have been interpreted as being met.
In relation to claim 57, SEQ ID NO:17 of 255 is acetylated at the N-terminus (per the sequence listing).
Claims 1, 57 and 79 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9789164 (164 as cited with IDS 12/21/22). Although the claims at issue are not identical, they are not patentably distinct from each.
164 recites SEQ ID NO:18 (claim 1) and a composition with a carrier (claim 4).
In relation to the composition of the instant claims 1 and 79, 164 expressly recites a composition with a carrier (claim 4).
In relation to the sequence of claim 1, SEQ ID NO:18 of 164 comprises instant SEQ ID NO:8 with 3 substitutions (at positions 9, 10 and 16). Since the structural limitations are met, the functional limitations have been interpreted as being met.
In relation to claim 57, SEQ ID NO:18 of 164 is acetylated at the N-terminus (per the sequence listing).
Response to Arguments – double patenting
Applicant's arguments filed 9/12/25 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants refer to the recitation of SEQ ID NO:8, a close reading of claim 1 reveals that it allows for ‘3 amino acid substitutions’. Thus, claim 1 is not limited to SEQ ID NO:8. The claim limitations are met for the reasons set forth above.
Conclusion
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658