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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 1, 2026 has been entered with the RCE filed on June 15, 2026.
Status of the Claims
Claims 1-105 were originally filed February 21, 2023.
The amendment received June 23, 2023 cancelled claims 1-105 and added new claims 106-125.
The amendment received November 21, 2025 amended claim 106.
The amendment received March 23, 2026 amended claim 106 and canceled claims 107-115 and 117-125.
The amendment received June 1, 2026 and entered with the RCE filed June 15, 2026 amended claim 106 and added new claims 126-135.
Claims 106, 116, and 126-135 are currently pending.
Claim 106, 126, and 129-131 is currently under consideration.
Please note: one of skill in the art would presume that C (see X1 in independent claim 106) is cysteine. The originally filed specification does not define C as carbamidomethylcysteine (i.e. a specific definition section comprising defining C as carbamidomethylcysteine). Therefore, the limitation in withdrawn claim 107 is indefinite and fails to further limit independent claim 106 because it goes against the art recognized definition of C. Please note: this is a reminder to applicant regarding past limitations in the claims.
Please note: not all of the peptides would have a lysine at residue 14. In fact, most of the peptides would be 12mers. Therefore, withdrawn claim 114 requires clarification. Please note: this is a reminder to applicant regarding past limitations in the claims.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 106-116) in the reply filed on November 21, 2025 is acknowledged. Claims 117-125 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method (incorrectly designated as a composition on page 4 of the response received November 21, 2025 – see line 12), there being no allowable generic or linking claim.
Applicants elected, without traverse, of GWLAYPDSVPYRPK as the first subunit (the N-terminal G was elected for X1 as “a first spacer”; X2 is a combination of R and P-K), AWLAYPDSVPYRPK (X1 is A; X2 is a combination of R and P-K), and Q-Q and G-G as the additional components in the reply filed on November 21, 2025 is acknowledged.
Applicants elected QQGWLAYPDSVPYRPKGGAWLAYPDSVPYRPK as “the species of A, B and C collectively.”
Please note: It is presumed that the peptides of SEQ ID NO: 9 are written in N-terminus to C-terminus order. Therefore, the elected species is linked via the C-terminus of the first subunit (N-terminus-QQGWLAYPDSVPYRPK-C-terminus) to the N-terminus of the second subunit (N-terminus-AWLAYPDSVPYRPK-C-terminus) with an intervening GG linker. Therefore, the N-terminus to C-terminus or N-terminus to N-terminus linkage of present independent claim 106 does not read on the elected species. This is believed to be in error and the claim has still been examined. See the new matter rejection below.
Claims 107-116, 127, 128, and 132-135 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 21, 2025.
Please note: claim 116 is withdrawn because applicants did not elect a pharmaceutically acceptable excipient for species C. Applicants can not traverse a species election after an election without traverse and/or change the species election (election by original presentation). See page 5 “Claim 116 in Relation to the Restriction Requirement” section of the response received June 1, 2026.
Please note: claim 127 is withdrawn because the elected species is not configured in an N-terminus to C-terminus order (see above and the new matter rejection below).
Please note: claim 128 is withdrawn because the elected species is not configured in an N-terminus to N-terminus order (see above and the new matter rejection below).
Please note: claim 132 is withdrawn because only alanine was elected and not a biotinylated alanine (X1 is alanine for the second subunit).
Please note: claim 133 is withdrawn because SEQ ID NO: 23 (AWLAYPDSVPYRPK) was elected as the second subunit (i.e. not the first subunit as claimed).
Please note: claim 134 is withdrawn because SEQ ID NO: 6 (GAWLAYPDSVPYRPK) was not elected.
Please note: claim 135 is withdrawn because SEQ ID NO: 6 (GAWLAYPDSVPYRPK) was not elected. GWLAYPDSVPYRPK was elected as the first subunit (i.e. not part of the originally filed sequence listing or the new sequence listing filed June 1, 2026). Please note: GWLAYPDSVPYRPK does read on the variable sequence of SEQ ID NO: 9.
Please note: typically, applicants should supply a SEQ ID NO: for any sequences being discussed during prosecution. However, since GWLAYPDSVPYRPK is not part of the present sequence listing, this would be impossible. AWLAYPDSVPYRPK is present SEQ ID NO: 23. GWLAYPDSVPYRPK and AWLAYPDSVPYRPK (SEQ ID NO: 23) while being members of the Markush Group for independent claim 106, are not specifically claimed species per se. Thus, GWLAYPDSVPYRPK and AWLAYPDSVPYRPK (SEQ ID NO: 23) are not required for any rejection of record.
Please note: QQ is not part of the Markush Group for X1 and is not part of the present claims. Therefore, QQ is not required for any rejection of record. QQ is also not disclosed in the originally filed specification and would be considered new matter if added to the claims.
Please note: GG, as elected would be a combination of R, P-K, and “a second spacer” for X2 of the first subunit.
The examiner of record has provided a comprehensive analysis regarding the elected species (see pages 4-5 of the response received March 23, 2026; see above). The elected species is not part of the present claims and includes new matter. Therefore, the elected species of QQGWLAYPDSVPYRPKGGAWLAYPDSVPYRPK was not searched.
Potential Rejoinder
Applicant elected claims directed to a product. If a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all the criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to a rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Priority
The present application is a CON of PCT/US2021/050294 filed September 14, 2021 which claims the benefit of 63/078,241 filed September 14, 2020.
Withdrawn Objections
The objection to the disclosure regarding Table 5 appears to be missing is withdrawn in view of the amendment received June 1, 2026 renaming Table 6 as Table 5.
New Objections Necessitated by Amendment
Specification
The amendment filed June 1, 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: withdrawn claims 127 and 128 are considered new matter (i.e. an N-terminal to C-terminal configuration or an N-terminal to N-terminal configuration are not taught in the originally filed specification).
Applicant is required to cancel the new matter in the reply to this Office Action.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 106 is objected to because of the following informalities: “(N to C)” and “(N to N)” should be written as N-terminus and C-terminus to avoid confusion with the N/Asn and C/Cys amino acids. Appropriate correction is required.
Claim 106 is objected to because of the following informalities: “C terminus” should read “C-terminus” (see line 8). Appropriate correction is required.
Claim 106 is objected to because of the following informalities: “a N-terminus” should read “an N-terminus” (see line 10). Appropriate correction is required.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3. Any claim requiring a specific percent identity, necessarily requires at least the recited percent identity.
Withdrawn Rejections
The rejection of claim 106 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 (new matter regarding the first spacer being G) is withdrawn in view of the disclosure in originally filed paragraph 5 (i.e. X1 can be any amino acid in Table 1 – pages 13 and 14 - including G). While not disclosed as a linker, the amino acid may be present.
New Rejections Necessitated by Amendment
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 106, 126, and 129-131 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The originally filed specification does not provide support for “wherein the first subunit and second subunit are configured in the peptide: (i) in an N-terminus to C terminus (N to C) order, wherein the N-terminus of the first or second subunit is linked to the C-terminus of the second or first subunit; or (ii) in a N-terminus to N-terminus (N to N) order, wherein the N-terminus of the first subunit is linked to the N-terminus of the second subunit via a linker”.
The above would presumably result in the following structures which are not taught in the originally filed specification.
C-terminus-first subunit-N-terminus-C-terminus-second subunit-N-terminus (i.e. both peptides in the reverse order)
C-terminus-second subunit-N-terminus-C-terminus-first subunit-N-terminus (i.e. both peptides in the reverse order)
C-terminus-first subunit-N-terminus-linker-N-terminus-second subunit-C-terminus (i.e. first subunit in the reverse order)
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 106, 126, 129, 130, and 131 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. One of skill in the art would not be able to determine the scope of the present claims. For example, see the “Sequence Interpretation” section above. It is unclear what percent identity is required for present SEQ ID NO: 9.
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.
Claim 106, 126, 129, 130, and 131 are rejected under 35 U.S.C. 103 as being unpatentable over Gomez-Soler et al., May 31, 2019, Engineering nanomolar peptide ligands that differentially modulate EphA2 receptor signaling, J Biol Chem, 294(22): 8791-8805 (provided in the IDS; a clearer version of the NPL was provided with the Non-Final Office Action); Duggineni et al., 2013, Design and Synthesis of Potent Bivalent Peptide Agonists Targeting the EphA2 Receptor, ACS Medical Chemistry Letters, 4: 344-348 (provided in the IDS; a clearer version of the NPL was provided with the Non-Final Office Action); and Chen et al., 2013, Fusion protein linkers: Property, design and functionality, Advanced Drug Delivery Reviews, 65: 1357-1369.
For present claims 106, 126, 129, 130, and 131, Gomez-Soler et al. teach EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, G is a linker, X2 is RPK, EphA2 ligand binding domains with different C-terminus amino acids (i.e. different) (please refer to the entire reference particularly the abstract; Table 1 – Identifier numbers 9-22; Figures 2, 4, 6).
However, Gomez-Soler et al. do not teach dimers.
For present claims 106, 126, 129, 130, and 131, Duggineni et al. teach dimers of EphA2 ligand binding domains comprising SWLAYPGAVSYR (bold and underlined are the same as present SEQ ID NO: 9) and disulfide linkage (please refer to the entire reference particularly the abstract; Figures 1-3).
For present claims 106, 126, 129, 130, and 131, Chen et al. teach glycine linkers (G)n and disulfide linkages (please refer to the entire specification particularly sections 3.1, 5.1, 5.2, 5.3; Tables 2 and 3).
All the claimed elements were known (e.g. EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, Gn is a linker, X2 is RPK; dimers of EphA2 ligand binding domains) in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. binding to EphA2 receptors) and the combination would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because the substitution of one known element (i.e. monomer) for another (i.e. dimer) would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making dimers in any orientation) was recognized as part of the ordinary capabilities of one skilled in the art. The claim would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Maintained and/or Modified* Rejections
*wherein the modification is due to 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.
Claim 106, 126, 129, 130, and 131 are rejected under 35 U.S.C. 103 as being unpatentable over Gomez-Soler et al., May 31, 2019, Engineering nanomolar peptide ligands that differentially modulate EphA2 receptor signaling, J Biol Chem, 294(22): 8791-8805 (provided in the IDS; a clearer version of the NPL was provided with the Non-Final Office Action) and Duggineni et al., 2013, Design and Synthesis of Potent Bivalent Peptide Agonists Targeting the EphA2 Receptor, ACS Medical Chemistry Letters, 4: 344-348 (provided in the IDS; a clearer version of the NPL was provided with the Non-Final Office Action).
For present claims 106, 126, 129, 130, and 131, Gomez-Soler et al. teach EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, G is a linker, X2 is RPK, EphA2 ligand binding domains with different C-terminus amino acids (i.e. different) (please refer to the entire reference particularly the abstract; Table 1 – Identifier numbers 9-22; Figures 2, 4, 6).
However, Gomez-Soler et al. do not teach dimers.
For present claims 106, 126, 129, 130, and 131, Duggineni et al. teach dimers of EphA2 ligand binding domains comprising SWLAYPGAVSYR (bold and underlined are the same as present SEQ ID NO: 9) and disulfide linkage (please refer to the entire reference particularly the abstract; Figures 1-3).
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups; G linker verses GG linker) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); and Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
All the claimed elements were known (e.g. EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, G is a linker, X2 is RPK; dimers of EphA2 ligand binding domains) in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. binding to EphA2 receptors) and the combination would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because the substitution of one known element (i.e. monomer) for another (i.e. dimer) would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making dimers in any orientation) was recognized as part of the ordinary capabilities of one skilled in the art. The claim would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Gomez-Soler et al. and Duggineni et al. for claim 106 were considered but are not persuasive for the following reasons.
Applicants contend that Gomez-Soler et al. and/or Duggineni et al. do not teach the presently claimed linkage. Applicants appear to argue unexpected results of increased potency.
Applicants’ arguments are not convincing since the teachings of Gomez-Soler et al. and Duggineni et al. render the composition of the instant claims prima facie obvious.
The claim would have been obvious because a particular known technique (i.e. making dimers in any orientation) was recognized as part of the ordinary capabilities of one skilled in the art. The claim would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Duggineni et al. teach that dimerization alone increases potency by 13 fold (please refer to the entire reference particularly the abstract; i.e. dimerization is expected to provide increased potency).
Gomez-Soler et al. teach that making a S1A mutation increased potency by approximately two fold (please refer to the entire specification particularly Table 1; page 8795 first full paragraph; i.e. mutations are known to increase potency).
In response to applicant's arguments against the references individually, 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).
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 106, 126, and 129-131 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,398,179 in view of Gomez-Soler et al., May 31, 2019, Engineering nanomolar peptide ligands that differentially modulate EphA2 receptor signaling, J Biol Chem, 294(22): 8791-8805 (provided in the IDS; a clearer version of the NPL was provided with the Non-Final Office Action); Duggineni et al., 2013, Design and Synthesis of Potent Bivalent Peptide Agonists Targeting the EphA2 Receptor, ACS Medical Chemistry Letters, 4: 344-348 (provided in the IDS; a cleaner version of the NPL was provided with the Non-Final Office Action); and Chen et al., 2013, Fusion protein linkers: Property, design and functionality, Advanced Drug Delivery Reviews, 65: 1357-1369.
U.S. Patent No. 12,398,179 claims (bA/present X1)(WL/X1)-AYPDSVP- (YK/YSK/YGSK/YGSGK/YR/X2) – present X2 wherein G and S are linkers (i.e. EphA2 ligand binding domains).
Gomez-Soler et al. teach EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, G is a linker, X2 is RPK, EphA2 ligand binding domains with different C-terminus amino acids (i.e. different) (please refer to the entire reference particularly the abstract; Table 1 – Identifier numbers 9-22; Figures 2, 4, 6).
Duggineni et al. teach dimers of EphA2 ligand binding domains comprising SWLAYPGAVSYR (bold and underlined are the same as present SEQ ID NO: 9) and disulfide linkage (please refer to the entire reference particularly the abstract; Figures 1-3).
Chen et al. teach glycine linkers (G)n and disulfide linkages (please refer to the entire specification particularly sections 3.1, 5.1, 5.2, 5.3; Tables 2 and 3).
All the claimed elements were known (e.g. EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, Gn is a linker, X2 is RPK; dimers of EphA2 ligand binding domains) in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. binding to EphA2 receptors) and the combination would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because the substitution of one known element (i.e. monomer) for another (i.e. dimer) would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making dimers in any orientation) was recognized as part of the ordinary capabilities of one skilled in the art. The claim would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 12,398,179 in view of Gomez-Soler et al. and Duggineni et al. for claim 106 were considered but are not persuasive for the following reasons.
Applicants contend that the amendments received June 1, 2026 and entered with the RCE filed June 15, 2026 negates the rejection.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 12,398,179 in view of Gomez-Soler et al., Duggineni et al., and Chen et al. renders obvious the composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
U.S. Patent No. 12,398,179 claims (bA/present X1)(WL/X1)-AYPDSVP- (YK/YSK/YGSK/YGSGK/YR/X2) – present X2 wherein G and S are linkers (i.e. EphA2 ligand binding domains).
Gomez-Soler et al. teach EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, G is a linker, X2 is RPK, EphA2 ligand binding domains with different C-terminus amino acids (i.e. different) (please refer to the entire reference particularly the abstract; Table 1 – Identifier numbers 9-22; Figures 2, 4, 6).
Duggineni et al. teach dimers of EphA2 ligand binding domains comprising SWLAYPGAVSYR (bold and underlined are the same as present SEQ ID NO: 9) and disulfide linkage (please refer to the entire reference particularly the abstract; Figures 1-3).
Chen et al. teach glycine linkers (G)n and disulfide linkages (please refer to the entire specification particularly sections 3.1, 5.1, 5.2, 5.3; Tables 2 and 3).
All the claimed elements were known (e.g. EphA2 ligand binding domains comprising AWLAYPDSVPY(R/RPK) wherein X1 is A, Gn is a linker, X2 is RPK; dimers of EphA2 ligand binding domains) in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. binding to EphA2 receptors) and the combination would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because the substitution of one known element (i.e. monomer) for another (i.e. dimer) would have yielded predictable results (i.e. higher binding affinity) to one of ordinary skill in the art at the time of the invention. The claim would have been obvious because a particular known technique (i.e. making dimers in any orientation) was recognized as part of the ordinary capabilities of one skilled in the art. The claim would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
In response to applicant's arguments against the references individually, 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).
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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