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
Applicant’s election without traverse of the compound of claim 37 in the reply filed on September 16, 2025, is acknowledged.
The elected species was searched. Dependent claim 37 limited to this species is free of the prior art. The full scope of the amended claims has been searched and is free of the prior art.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located throughout the specification including in claims 22 and 37, pages 37-114 and 165, Examples 2-28, and Tables 9 and 12. The requirement applies to sequences depicted as chemical formulas as well as with three-letter and single-letter coded amino acids. In addition, the CRF contains numerous errors. For example, SEQ ID NO: 47 lists acetyl in position 1 and Met in position 2. However, acetyl is not an amino acid. The peptide contains methionine modified with an acetyl at the N-terminus at position 1. The CRF should be consistent with the structure of the peptide. This type of error appears throughout the CRF.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 5 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application Nos. PCT/EP2020/069308, EP19198810.4, and EP19000325.1 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Amended claims 1 and 2 and each of their dependent claims 5, 8, 11-15, 22-25, 29, 31, 33-36, and 38 are not supported for the same reasons given in the rejection under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph below.
Therefore, the earliest effective filing date of claims 1-2, 5, 8, 11-15, 22-25, 29, 31, 33-36, and 38 is the filing date of the instant application, January 6, 2022.
The prior-filed applications, Application Nos. PCT/EP2020/069308, EP19198810.4, and EP19000325, disclose the species in claim 37. Therefore, the earliest effective filing date of claim 37, which is limited in scope to the single species, is the filing date of EP19000325.1, July 8, 2019.
Claim Rejections - 35 USC § 112(a)
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, 2, 5, 8, 11-15, 22-25, 29, 31, 33-36, and 38 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.
Independent claims 1 and 2 have each been amended to narrow the scope of formula I to a subgenus wherein Xaa1 is formula (II); Xaa2 is formula (III); Xaa3 is formula (V) wherein X3 is CH2, p is 1, and R3a is H; Xaa4 is formula (VI) wherein R4a is OH, q is 1 wherein one or two hydrogens of the CH2 group may be substituted with methyl, ethyl, (C5-C6)aryl or (C5-C6)heteroaryl; Xaa5 is formula (VII) wherein R5 is OH and r is 2; Xaa6 is an aromatic L-amino acid; Xaa7 is formula (IX) wherein t is 1; Yc is formula (X) wherein substitution is meta, Y1 is CH and Y2 is CH; n is 0; t is 1; and wherein an amino acid Aaa is attached to Xaa1 at the N-terminus. In claim 1, R7a is -CO-, which allows for the peptide to terminate at Xaa7 or extend. In claim 2, R7a is -CO-XXX wherein XXX is an amino acid or a peptide, wherein the amino acid or peptide are optionally substituted by Z, wherein Z is a chelator with an optional linker.
Claims 11-15, 22-23, 25, 29, 31, and 33-36 depend from claim 1. Claims 11-12 limit the scope of the Aaa at the N-terminus but leaves all other positions as defined in claim 1. Claims 13-14 limit Xaa1 and Xaa2, respectively, but leaves all other positions as defined in claim 1. Claim 15 limits Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7 but leaves Aaa and R7a as defined in claim 1. Claims 22-23 and 25 limit R7a but leave all other positions as defined in claim 1. Claims 29 and 33-36 require that the cyclic peptide of claim 1 further comprises a radionuclide. Claim 31 recites a composition comprising the cyclic peptide of claim 1.
Claims 5, 8, 24, and 38 depend from claim 2. Claims 5 and 24 require the chelator but leave all other groups as defined in claim 2. Claim 8 limits the scope of the Aaa at the N-terminus but leaves all other positions as defined in claim 2. Claim 38 recites a composition comprising the cyclic peptide of claim 1.
Neither the subgenus set forth in amended claims 1 nor 2, or their dependent claims, literally appear in the originally-filed disclosure. Therefore, the amendment to claims 1 and 2, and by extension to their dependent claims, is not expressly supported in the specification.
Three species of the amended subgenera are disclosed in the original specification:
Ac-Met-[Cys(3MeBn)-Aib-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3204, SEQ ID NO: 42); Ac-Met-[Cys(3MeBn)-Gly-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3214, SEQ ID NO: 47); and Ac-Met-[Cys(3MeBn)-ala-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3215, SEQ ID NO: 48). All three species contain Ac-Met-[Cys(3MeBn)-Xaa2-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2. In the subgenera, the N-terminal amino acid can be any structure but is limited to Ac-Met in all three species. In the subgenera, Xaa4 maybe be modified at the CH2 of formula (VI) but Xaa4 is limited to Thr wherein CH2 is unmodified in all three species. In the subgenera, Xaa6 maybe any aromatic L-amino acid but is limited to Phe in all three species. In the subgenera, R7a may be any amino acid or peptide with or without a chelator but is limited to the single peptide Asp-His-Phe-Arg-Asp-NH2 without a chelator in all three species. Therefore, these species, which are limited in scope and variation, are not representative of the full scope of the amended subgenera.
In addition, the specification fails to provide any description or guidance that would reasonably lead one of ordinary skill in the art to the particular subgenus recited in claims 1 and 2. Therefore, the amendment to claims 1 and 2 is not implicitly or inherently supported in the specification.
Accordingly, only new claim 37 meets the written description requirements of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 14, which depends from claim 1, permits Xaa3 to be a Pro derivative, Xaa4 to be a Thr derivative, and Xaa5 to be a Glu derivative. Table 6 of the specification states that Pro derivatives include Aze, Pip, Hyp, Tfp, Cfp, Dmp, Tap, H3p, 4Ap, Cpp, Hym, Chy, and Dfp. Table 6 of the specification states that Thr derivatives include Ser, Homoserine, and allo-Thr. Table 6 of the specification states that Glu derivatives include Asp, Asn, Gn, Cya, homoGlu, and gamma-hydroxy Glu. However, claim 1 limits Xaa3 to Pro, Xaa4 for formula (VI) and Xaa5 to Glu. Therefore, claim 14 does not include all the limitations of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Citation of Pertinent Art
The earliest effective filing date of claims 1-2, 5, 8, 11-15, 22-25, 29, 31, 33-36, and 38 is the filing date of the instant application, January 6, 2022. WO 2021/005131 is not prior art under 35 U.S.C. 102(a)(1) over these claims because it was published within one year of the earliest effective filing date on January 14, 2021, and has the same identical inventive entity. WO 2021/005131 is not prior art under 35 U.S.C. 102(a)(2) over these claims because it was filed prior to the effective filing date but has the same identical inventive entity. EP3763726 is not prior art under 35 U.S.C. 102(a)(1) over these claims because it was published within one year of the earliest effective filing date on January 13, 2021, and has the same identical inventive entity.
Allowable Subject Matter
Claim 37 would be allowable if rewritten to overcome the objection for sequence compliance, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
WO 2019/083990 A2 (cited by Applicant) discloses imaging and radiotherapeutic agents targeting fibroblast-activation protein-a that are structurally unrelated to the instantly claimed compounds (abstract).
WO 2004/07706 (cited by Applicant) discloses macrocyclic structures that are cyclized by a moiety identical to instant Yc (Figure 2). However, the reference nowhere teaches nor suggests the peptide sequences recited in the instant claims.
The following claims drafted by the examiner and considered to distinguish patentably over the art of record in this application, are presented to applicant for consideration:
Delete claim 1 and insert --A compound comprising a cyclic peptide selected from the group consisting of:
Ac-Met-[Cys(3MeBn)-Aib-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (SEQ ID NO: 42);
Ac-Met-[Cys(3MeBn)-Gly-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (SEQ ID NO: 47); and
Ac-Met-[Cys(3MeBn)-ala-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (SEQ ID NO: 48);
wherein Aib is 2-amino-isolutyric acid, ala is D-alanine, and Cys(3MeBn) is
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264
245
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, and wherein the squiggly line indicates the linkage to the cysteine at position 8 via a thioether bond; and wherein the cyclic peptide is optionally covalently attached to a chelator.--
Cancel claims 2, 5, 8, 11-15, 22, and 38.
Delete claim 23 and insert --The compound of claim 1 wherein the cyclic peptide is covalently attached to a chelator via a linker at the Asp at position 13 of the cyclic peptide.--
Delete claim 24 and insert --The compound of claim 1 wherein the cyclic peptide is covalently attached to a chelator via a linker at the Met at position 1 of the cyclic peptide.--
Delete claim 25 and insert --The compound of claim 1 wherein the cyclic peptide is covalently attached to a chelator via a linker at the Cys(3MeBn) at position 3 of the peptide.--
In claim 29, delete “claim 1” and insert --claim 23-- therefor.
In claim 29, line 2, insert --further—prior to comprises.
Allow claims 31 and 33-36 as previously presented.
In claim 37, insert --(SEQ ID NO: 47)-- after the structure.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654