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 10/21/25 are acknowledged.
Any rejection or objection from the 5/21/25 office action not addressed below is withdrawn based on the amendments.
Previously, Group 1 and the species of SEQ ID NO: 169 were elected. SEQ ID NO:169 (the elected species) was previously deleted from claim 4 and the current claim has a proviso excluding SEQ ID NO: 169. The examination was then extended to the extent necessary to determine patentability (MPEP 803.02 III A). In the instant case, the search was extended to SEQ ID NO:181.
Although unclear, newly added claim 31 has been interpreted such that SEQ ID NO:181 is within the scope of the claim. Newly added claim 32 is included in the instant examination.
Claims 11, 18-19, 28 and 30 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/23/21.
Claims 1-3, 5-6, 8 and 22-26 have been canceled.
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are being examined.
Priority
The priority information is found in the filing receipt dated 9/24/24.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/21/25 has been considered by the examiner.
Claim Rejections - 35 USC § 112
This rejection is a new rejection necessitated by the addition of new claim 31.
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.
Claim 31 is 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 31 refers to various options for X1-X5. However, it is unclear if each or only one of the options is required. In the instant case, the 2nd to last line of the claim does not end in ‘or’ or ‘and’. Without such words the claim scope is unclear. For example, if the word ‘or’ at the end of the 2nd to last line of the claim is intended then the scope is broader than if the word ‘and’ is intended to be at the end of the 2nd to last line of the claim. Further, X1-X5 only appear in several of the sequences recited in claim 4. It is unclear if sequences with positions corresponding to X1-X5 are intended to fall within the scope of the claim. For example, SEQ ID NO:181 comprises CM where C corresponds to Cii and M corresponds to the X1 position. Although SEQ ID NO:181 does not specifically recited X1, it is unclear if SEQ ID NO:181 falls within the scope of claim 31. Since SEQ ID NO:181 contains M at a position that corresponds to X1, SEQ ID NO:181 has been interpreted as reading on claim 31.
Double Patenting
Claims were previously rejected under double patenting. The rejections are updated due to the addition of new claims 31-32. Further, since application 18424386 has matured to US 12435107 and application 18906616 has matured to US 12459974 the corresponding rejections are updated accordingly. In addition, the claims of application 17630747 have been amended so the corresponding rejection is updated accordingly.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 21-38 of copending Application No. 17663169 (reference application; ‘169’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
169 recites SEQ ID NO: 15 (claim 1) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). 169 recites pharmaceutically acceptable excipients (claim 26). 169 recognizes administration of the peptides (claim 27 for example).
169 does not recite a specific sequence that reads on the instant claims nor does 169 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27). Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 169 because 169 recites bicyclic peptides for particular uses (claim 27). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:15 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42). Further, in Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 169 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 169 expressly recites for Nectin-4 (claim 1).
In relation to claim 12, 169 recites specific salts including sodium (claim 33).
In relation to claim 29, 169 recites pharmaceutically acceptable excipients (claim 26).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-15, 18, 21-24 and 46 of copending Application No. 18271593 (reference application; ‘593’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
593 recites SEQ ID NO: 1 (claim 10) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). 593 recites methods of administering (claim 1).
593 does not recite a specific sequence that reads on the instant claims nor does 593 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 593 because 593 recites bicyclic peptides for particular uses (claim 1). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 593 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 593 expressly recites for Nectin-4 (claim 1).
In relation to claim 12, 593 recites salts (claim 8) and Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,435,107 (‘107’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
107 recites SEQ ID NO: 1 (claim 20) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 20).
107 does not recite a specific sequence that reads on the instant claims nor does 107 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 107 because 107 recites bicyclic peptides (claim 20). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 107 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 20). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. Since a structure as claimed is suggested, the structure would function as claimed.
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-38 of copending Application No. 18427414 (reference application; ‘414’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
414 recites SEQ ID NO: 1 (claim 21) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). 414 recites methods of administering (claim 37).
414 does not recite a specific sequence that reads on the instant claims nor does 414 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 414 because 414 recites bicyclic peptides for particular uses (claim 19). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 414 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 21). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 414 recites for Nectin-4 (claim 21).
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,912,792 (‘792’ as cited with IDS 7/31/24) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
792 recites SEQ ID NO: 1 (claim 1) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1).
792 does not recite a specific sequence that reads on the instant claims nor does 792 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 792 because 792 recites bicyclic peptides (claim 1). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 792 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. Since a structure as claimed is suggested, such structure would function as claimed.
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-43 of copending Application No. 18796898 (reference application; ‘898’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
898 recites BCY8245 (claim 30). BCY8245 structure is known (see pages 53-54 of the instant specification) and comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds. 898 recites methods of administering (claim 24).
898 does not recite a specific sequence that reads on the instant claims nor does 898 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 898 because 898 recites bicyclic peptides for particular uses (claim 30). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in BCY8245 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 898 recites BCY8245 (claim 30) which is a peptide that comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds. CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 898 recites for targeting Nectin-4.
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44 and 67-91 of copending Application No. 17630747 (‘747’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
747 recites SEQ ID NO: 1 (claim 79) where the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 44).
747 does not recite a specific sequence that reads on the instant claims nor does 747 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 747 because 747 recites bicyclic peptides (claims 44 and 79). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 747 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claims 44 and 79). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 747 recites for Nectin-4 (claim 67)
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-64 of copending Application No. 18802865 (‘865’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
865 recites BCY8245 (claim 50). BCY8245 structure is known (see pages 53-54 of the instant specification) and comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds.
865 does not recite a specific sequence that reads on the instant claims nor does 865 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27). Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 865 because 865 recites bicyclic peptides (claim 50). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in BCY8245 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 865 recites BCY8245 (claim 50) which comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds. CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 865 recites for Nectin-4 (claim 45)
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 17926454 (‘454’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
This is a provisional nonstatutory double patenting rejection.
454 recites BT8009 (claim 1) which is defined as comprising BCY8234 (page 5 of the specification).
454 does not recite a specific sequence that reads on the instant claims nor does 865 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27). Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 454 because 454 recites bicyclic peptides (claim 1). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in BT8009 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 454 recites BT8009 (claim 50) which comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds. CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. Since a structure as recited in the claims is suggested, it would function as claimed.
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,970,553 (‘553’ as cited with IDS 7/31/24) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
553 recites SEQ ID NO:1 (claim 1) and salts (claim 10) and pharmaceutical compositions (claim 21).
553 does not recite a specific sequence that reads on the instant claims nor does 792 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27). Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 553 because 553 recites bicyclic peptides (claim 1). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in SEQ ID NO:1 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 553 recites that the peptide comprises 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 1). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. 553 recites for binding Nectin-4 (claim 1).
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Claims 4, 7, 9-10, 12-17, 20-21, 27, 29 and 31-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,459,974 (‘974’) in view of Teufel et al. (WO 2016/067035; first cited 11/23/21; ‘Teufel’).
974 recites a particular sequence (claim 1).
974 does not recite a specific sequence that reads on the instant claims nor does 974 teach the additional groups of claims 14-17 and dependents.
Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] at the N-terminus to facilitate the conjugation of effector groups and retention of potency (claim 12 and first paragraph of page 12). Teufel teach linkers that can be cleaved to release the toxin (page 60 last complete paragraph) and specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61) where MMAE is monomethyl auristatin E (page 23). Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph). Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach bicyclic peptide ligands (title) and teach the pharmaceutically acceptable salt is sodium (claim 23). Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph). Teufel specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16). In Table 8, Teufel shows that the 1-Nal and 2-Nal substitutions had the best activity and actually enhanced activity (pages 53-54). Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 974 because 974 recites bicyclic peptides (claim 11). Since Teufel teach the inclusion of non-natural amino acids that are not recognized by proteases (page 12 3rd paragraph) and specifically recites that the non-natural amino acid can be 1-naphthylalanine (1-Nal) or 2-naphthylalanine (2-Nal) (page 12 last 2 paragraphs and claim 16) one would have been motivated to replace 1-Nal with 2-Nal in the sequence of claim 1 of 974 resulting in CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Teufel teach the capping of the N-terminus via acetylation (page 52 first paragraph and examples) so one would have been motivated to do such resulting in Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC. Since Teufel teach bicyclic peptide ligands (title) and teach the inclusion of a [B-Ala][Sar10] and specifically teach Val-Cit-PABC-MMAE (page 61) one would have been motivated to add such groups to the peptide. Since Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph) and teach a combination with one or more pharmaceutically acceptable excipients (claim 40) one would have been motivated to do such. One would have had a reasonable expectation of success since Teufel teach synthesis of compounds (pages 41-42).
In relation to the peptide of claims 4, 7, 9-10, 13 and 31, 974 recites sequences which comprise 3 cysteines separated by 2 loop sequences and a molecular scaffold which forms covalent bonds (claim 11). CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC as discussed above is instant SEQ ID NO:181 as recited in claim 4 and reads on SEQ ID NO:204 of claim 7. Ac-CP[2Nal][dD]CM[HArg]DWSTP[HyP]WC reads on BCY8175 of claims 9-10. Since a structure as recited in the claims is suggested, it would function as claimed.
In relation to claim 12, Teufel teach salts including sodium (claim 23).
In relation to claim 29, Teufel recites pharmaceutically acceptable excipients (claim 10).
In relation to claim 20, Teufel teach a combination with one or more pharmaceutically acceptable excipients (claim 40).
In relation to claim 21, Teufel teach the inclusion of further agents (page 22 last sentence of 3rd paragraph).
In relation to the conjugates of claims 14-17 and 27, Teufel specifically teach glutaryl-Val-Cit-PABC-MMAE (page 61).
In relation to claim 32, Teufel specifically teach the inclusion of a cytotoxic agent (claims 13 and 27).
Response to Arguments – double patenting
Applicant's arguments filed 10/21/25 have been fully considered but they are not persuasive.
Although applicants argue about a terminal disclaimer, the only terminal disclaimer of record is dated 7/12/22 and it does not address any of the instant rejections.
Although applicants argue about situations in which ‘allowable subject matter is identified’, such situation does not currently exist based on the rejections set forth above.
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.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
Prosecution Insights