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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 12/22/2025 wherein claims 1-10 and 13-15 were canceled; the specification and claims 11 and 12 were amended; and claims 16-28 were added. In addition, the Examiner acknowledges receipt of the amendment filed 5/4/2026 wherein claims 1-10 and 13-15 were canceled and claims 11 and 16 were amended.
Note(s): Claims 11, 12, and 16-28 are pending.
Priority/Priority Document
This application is a 371 of PCT/JP2020/039076 filed 10/16/2020 which claims benefit to JAPAN JP2019-191561 filed 10/18/2019.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 USC 119 (a) – (d). The certified copy has been filed in the pending application] on 4/15/2022.
While a certified copy of the prior document was submitted, an English language translation is not of record. Should Applicant desire to obtain the benefit of foreign priority under 35 USC 119 (a) – (d) prior to declaration of an interference, a certified English language translation of the foreign application should be submitted. 37 CFR 41.154(b) and 41.202(e). Failure to prove the certified translation may result in no benefit being accorded for the non-English document.
Note(s): The earliest effective filing date is 10/16/2020. While the Japan document was provided, it was not accompanied by an English translation or English equivalent.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 12/22/2025 and 5/4/2026 to the rejection of claim 11 made by the Examiner under 35 USC 103 and/or 112 have been fully considered and deemed persuasive for the reasons set forth below. Therefore, the said rejections are hereby WITHDRAWN.
112 Second Paragraph Rejections
The outstanding 112 second paragraph rejections are WITHDRAWN because Applicant amended the claims to overcome the rejections.
103 Rejection
The 103 rejection over Mamat et al (Journal of Labelled Compounds and Radiopharmaceuticals, March 2018, Vol. 61, pages 165-178) is WITHDRAWN because Applicant amended the claims to overcome the rejection.
Claim Interpretation
Amended independent claim 11 is directed to a radioactive metal-labeled antibody comprising a peptide and a radioactive metal complex (directly or indirectly linked to the peptide) conjugated to a triazole skeleton-containing structure represented by Formula (10a) OR a pyridazine skeleton-containing structure wherein Formula (10a) or said pyridazine skeleton containing structure is between the peptide and the radioactive metal complex.
Independent claims 25 and 27 are directed to a specific radioactive metal labeled antibody species
Applicant’s Election
Once again, Applicant's election with traverse of Group II (pending claims 11, 12, and 16-28) filed 5/13/2025 is acknowledged. The restriction requirement was deemed proper made FINAL.
Applicant elected the following species for initial examination wherein: (1) the diagnostic radionuclide is 89Zr and the therapeutic radionuclide is 225Ac; (2) the antibody is trastuzumab; (3) the peptide is GPDCAYH(Xaa2)GELVWCTFH wherein Xaa2 is lysine (K); (4) click reaction moiety is DBCO-azide; and (5) chelate is DOTAGA.
Note(s): Independent claim 11 requires a radionuclide, peptide, antibody and a triazole skeleton of formula 10a (see claim 11) or one having a pyridazine skeleton. Since Applicant did not select a specific skeleton, triazole, Formula (10a)
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, was elected by default since it was the first appearing skeleton in the claim.
The components of the elected species applicable to independent claim 11 are as follows: (1) the radionuclide is 89Zr or 225Ac; (2) the antibody is trastuzumab; (3) the peptide is GPDCAYH(Xaa2)GELVWCTFH wherein Xaa2 is lysine (K); (4) a skeleton of Formula (10a)
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is present; and (5) chelate is DOTAGA. Pending claims 11 and 16-23 reads on the elected species. Initially, the elected species was searched. Since prior art was not found to reject the elected species, the search was extended to all the species listed in claim 21 and no prior art was found. Thus, the search was once again extended to the species cited in the 103 rejection below. The search was not further extended because prior art was found which could reject the claims.
Withdrawn Claims
Claims 12 and 24-28 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Note(s): Claim 24 is directed to active steps incorporated in a method claims. Active steps are generally reserved for process/method claims. Thus, they are not included as independent claim 16 is directed to a product and it is unclear if Applicant intended the claim to be a product or process/method claim.
Information Disclosure Statement
The information disclosure statements filed 10/14/2025; 9/12/2025; 5/11/2026; and 5/26/2026 were considered.
NEW GROUNDS OR REJECTIONS
Written Description Rejection
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 11, 16-20, 22, and 23 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to amino acid sequences having the formula “(Xa)-Xaa1-(Xb)-Xaa2-(Xc)-Xaa3-Xd)...” other than the sequences disclosed in pending claim 21. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
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 11 and 16-23 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.
Claims 11 and 16-23: Independent claim 11 is ambiguous for the following reasons. (1) The claim is directed to a radioactive metal labeled antibody, but does not disclose that radioactive metal even though a radioactive metal complex is required. (2) Did Applicant intend ‘via’ (line 2) to be ‘comprising’ as it is unclear what are the actual components that must be present in the radioactive metal labeled antibody site. (3) The phrase ‘derived from a second atomic group’ in lines 6-7 is ambiguous. Specifically, while a second atomic group is disclosed in lines 28, it is set forth that ‘the second atomic group is a group comprising a linker and a moiety served from an azide or a cyclooctene’. Thus, it is unclear what is the actual structure of the second atomic group. A group derived from another group is indefinite as it does not require any particular portion of the parent structure (azide or cyclooctene) to be present in the derivative. (4) The claim is ambiguous because of the peptide formula which goes on to infinity. In line 6, it is disclosed that the peptide comprises an amino acid sequence consisting of 13-17 amino acid residues and is represent by Formula (i), “(Xa)-Xaa1-(Xb)-Xaa2-(Xc)-Xaa3-Xd)...”. In addition, the phrases ‘Xa, Xb, Xc, and Xd are continuous X in the number of a, continuous X in the number b, continuous X in the number of c, and continue X in the number of d’ (see lines 11-13) are ambiguous. (5) The phrase ‘one is amino acid residue derived from an amino acid having a thiol group in the side chain and the other is an amino acid residue derived from an amino acid having a haloacetyl group in the sidechain’ is ambiguous. Specifically, it is unclear what are the actual structures of the groups attached in Formula (i). What portion of the parent structure remains in the structure that is ‘derived from’ the designated substituents? (6) In lines 30-31, it is disclosed that ‘the radioactive metal contains a chelate site and a group derived from a first atomic group’. Lines 46-59 disclose that ‘the group derived from the first atomic group comprises a triazole skeleton containing structure’ represented by Formula (10a) or a pyridazine skeleton containing structure. Thus, it is unclear if the actual structure that is required is that of Formula (10a) or a pyridazine containing structure or if one is claiming derivatives of Formula (10a) and derivatives of pyridazine containing structures. (7) The claim is ambiguous because of the phrase ‘R2A represents the binding site to the remaining portion of the second atomic group’. Specifically, it is unclear what portion of or the second atomic group Applicant is referencing that and what ‘remaining’ portion of the structure the second atomic structure. What else is bound at this position such that there is a remaining portion of the structure left?
Since claims 16-23 depend upon independent claim 11 for clarity, those claims are also vague and indefinite.
Claim 16: The claim recites the limitation "the following formula (10a)" in line 48. There is insufficient antecedent basis for this limitation in the claim.
Claim 18: The claim is ambiguous because of the phrase ‘radioactive metal complex is derived from DOTAGA’. Specifically, it is unclear what portion of the parent structure remains in the derivative.
Claim 21, line 22: In the phrase ‘(Xaa1) and (Xaa3) both show homocysteine residues’, did Applicant intend to write, ‘(Xaa1) and (Xaa3) are both homocysteine residues’?
Claims 11 and 16-23: Independent claim 11 is ambiguous for the following reasons. According to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under, in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed to an amino acid sequence represented by Formula (i), “(Xa)-Xaa1-(Xb)-Xaa2-(Xc)-Xaa3-Xd)...” wherein Xa, Xb, Xc, and Xd are continuous X in the number of a, b, c, and d, respectively. X is an amino acid residue having neither a thiol group nor a haloacetyl group in the sidechain; a, b, c, and d are independently any integer not less than one and not more than 5 which satisfy a+b+c+d≤14; Xaa1 and Xaa3 are each independent an amino acid derived from an amino acid having a thiol group in the sidechain OR one is an amino acid residue derived from an amino acid an amino acid having a haloacetyl group in the side chain; Xaa 2 is lysine, arginine, cysteine, aspartic acid, glutamic acid, 2-aminosuberic acid, or diamino propionic acid; the second atomic group comprising a linker and a moiety derived from an azide or a cyclooctene; and the first atomic group comprises a triazole skeleton containing structure represented by Formula (10a) or a pyridazine skeleton containing structure.
Thus, the claim encompasses antibody complex defined by multiple Markush groups and subgroups thereof. As a result, pending claim 11 encompasses a massive number of distinct alternative members such that one skilled in the art cannot determine the metes and bounds of the claim. Thus, due to an inability to envision all of the compounds defined by the Markush groups, the claim is deemed to be vague and indefinite.
103 Rejection
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11, 16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Ghosh et al (J. Nucl. Med., 2017, Vol. 58, No. 11, pages 1858-1864).
Amended independent claim 11 is directed to a radioactive metal-labeled antibody comprising a peptide and a radioactive metal complex (directly or indirectly linked to the peptide) conjugated to a triazole skeleton-containing structure represented by Formula (10a) OR a pyridazine skeleton-containing structure wherein Formula (10a) or said pyridazine skeleton containing structure is between the peptide and the radioactive metal complex (see claim for details of the variable definitions of the various components therein).
Claim 16 is directed to a radioactive metal labeled antibody wherein the triazole skeleton containing structure is
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.
Claim 18 is directed to the radioactive metal complex being derived from DOTAGA.
Ghosh et al is directed to a dual labeling scaffold that enables a somatostatin receptor substance to retain its targeting properties (see entire document, especially, abstract). In particular, Ghosh et al disclose MMC(IR800)-TOC and DA(IR800)-TOC, see excerpts below, from Figure 3,page 1860, which discloses structures comprising Formula 10a, a chelator, and a peptide sequence which are components required for Applicant’s radioactive metal labeling antibody structure.
Structures from Figure 3, page 1860
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The structures (MMC(IR800)-TOC and DA(IR800)-TOC) were radiolabeled with 64Cu (a radioactive isotope of the metal) (see page 1862, Figure 5; Figure 6; and Figure 7). The structures MMC(IR800)-TOC and DA(IR800)-TOC comprise a peptide, a DOTAGA derivative as well as a
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substituent. Thus, the limitations of claims 11, 16, and 18 are met.
Specification
The disclosure is objected to because of the following informalities: the sequences referenced throughout the specification (see page 36), and in the claims, lack the proper sequence identification references. The sequence are generally listed with “SEQ ID No: ___” adjacent to the sequence. Applicant is respectfully requested to review MPEP 2422.01.V.
Appropriate correction is required.
Comments/Notes
The full scope of independent claim 11 was not searched.
Applicant is respectfully requested to incorporate the sequence identification numbers into claim 21. For example, replace ‘any one of sequences (1) – (14)’ with ‘any one of SEQ ID NO: 1 through SEQ ID NO: 14’. Each sequence in claim 21 should be referenced in such manner (see MPEP 2422.01.V).
It is respectfully requested that Applicant thoroughly review the pending claims for clarity of the claimed invention.
Conclusion
Claim 11 and 16-23 are rejected and claims 12 and 24-28 are withdrawn.
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.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
July 15, 2026
Prosecution Insights