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 .
Correction of the Record
In the restriction requirement mailed 3/14/2025, a typographical error appears. Specifically, ‘claim 1’ should be ‘claim 11’ for Group II (see excerpt below).
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Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 4/15/2022 wherein the specification was amended and claims 1-3, 5-7, 9, 10, and 12-14 were amended.
Note(s): Claims 1-15 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.
Claim Interpretation
Independent claim 1 is directed to a method for producing a radioactive metal-labeled antibody, comprising conducting a click reaction of a radioactive metal complex and a peptide-modified antibody wherein the click reaction is performed between a first atomic group of the radioactive metal complex and a second atomic group directly or indirectly linked to the peptide and wherein the second atomic group is an atomic group comprising an azide group or a trans-cyclooctene.
Independent claim 11 is directed to radioactive metal-labeled antibody site modified with a peptide wherein the radioactive metal complex is directly or indirectly linked to the peptide and a triazole skeleton-containing structure represented by Formula (10a) is present between the peptide and the radioactive metal complex OR a pyridazine skeleton-containing structure is present between the peptide and the radioactive metal complex:
Formula (10a)
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wherein RA is a binding site with a modified site or a chelate site, and RA is a binding site with a peptide.
Independent claim 13 is directed to a chelate linker comprising a chelate site coordinated to a radioactive metal, and a modified site to which a first atomic group capable of click reaction is bonded, wherein the first atomic group is an atomic group represented by the following formula (la) or (lb):
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wherein in formula (la), R1 is a binding site with a modified site or a chelate site, and in formula (1b), one of R3 and R4 is a binding site with a modified site or a chelate site and the other is a hydrogen atom, a methyl group, a phenyl group, or a pyridyl group.
Independent claim 14 is directed to peptide-modified antibody as set forth in detail therein.
Applicant’s Election
Applicant's election with traverse of Group II (claims 11 and 12) filed 5/13/2025 is acknowledged. Both the restriction requirement and the election of species requirement are being traversed. In summary, the traversal is on the grounds that the restriction is only proper the restricted groups are independent or patentably distinct and there is a serious burden placed on the Examiner if restriction is not required. This is found non-persuasive because for reasons on record and those found below.
According to MPEP 803.02, the Examiner may require and restriction and election of species. Specifically, according to MPEP 803.02.III.B, an election of species may be made at the Examiner’s discretion when multiple distinct species are present. The pending claims are directed to any peptide metal complex wherein the peptide may have any 13-17 amino acid residues as well as a second atomic peptide group (e.g., see claim 2). In addition, one may have a variety of structurally distinct chelates present (e.g., see claim 6) which are optionally present. Still, the claims read on various radionuclides (e.g., see claim 7) as well as groups comprising azide and trans-cyclooctene (e.g., see claim 1), structures having a triazole skeleton or any pyridazine containing structure (e.g., see claim 11), any chelate linker group comprising
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or
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(e.g., see claim 13), or complex comprising
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or
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(e.g., see claim 14). Thus, the pending invention encompasses a multitude of possible distinct structures/complexes.
Also, as indicated in the mailed restriction requirement, the invention has multiple distinct products with different special technical features and thus, lack unity of invention. Furthermore, as indicated by the cited prior art below, the invention has a ‘special technical feature’ that is well known in the prior art and it would be a burden on the Examiner to search the multitude of inventions/species encompassed by the pending claims. Hence, the restriction requirement is still deemed proper and is therefore 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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, is elected by default since it is 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. Claim 11 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 the species cited in the rejection below. The search was not further extended because prior art was found which could reject the claims.
Withdrawn Claims
Claims 1-10 and 12-15 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statement
The information disclosure statement filed 7/15/2022; 7/7/2024; 5/2/2024; 2/21/2024; 11/16/2023; 3/31/2025; 12/26/2024; 12/5/2024; 10/30/2024; & 8/15/2024 were considered.
Specification
The disclosure is objected to because of the following informalities: the structure appearing on page 51, paragraph [0143] of the specification is not readable. Applicant is respectfully requested to provide a readable copy of the structure.
Appropriate correction is required.
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.
Claim 11 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 11: The claim is ambiguous because it is the actual substance of Formula 10a is indefinite. ‘R1A is a binding site with a modified site or a chelate site’. ‘R2A is a binding site with a peptide’. Specifically, the definitions of the variables R1A and R2A are ambiguous. What is the modified site or specific binding site being referenced/claimed? Binding to what substance(s)? A chelate site? Similarly, R2A is a binding sites with a peptide. So, is it actually the peptide itself or a bond. In other words, the definitions given for R1A and R2A do not require that one have a substance bound at those position. The are binding site, but they could be opened (no substance(s) specifically bound to the structure). As a result, the metes and bounds of the claim are unclear.
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.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Mamat et al (Journal of Labelled Compounds and Radiopharmaceuticals, March 2018, Vol. 61, pages 165-178).
Independent claim 11 is directed to radioactive metal-labeled antibody site modified with a peptide wherein the radioactive metal complex is directly or indirectly linked to the peptide and a triazole skeleton-containing structure represented by Formula (10a) is present between the peptide and the radioactive metal complex OR a pyridazine skeleton-containing structure is present between the peptide and the radioactive metal complex:
Formula (10a)
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wherein RA is a binding site with a modified site or a chelate site, and RA is a binding site with a peptide.
Mamat et al is directed to radiolabeling applications for labeling compounds (peptides, proteins, and antibodies) (see entire document, especially, abstract). In Scheme 3 (see excerpt below), the ligation unit is between the building block and biologically active molecule (peptides, proteins, and antibodies, see abstract for definition). It should be noted the ligation unit is equivalent to Applicant’s Formula (10a) and the pyridazine skeleton that are disclosed in pending independent claim 11.
Scheme 3
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In Scheme 4 (see highlighted excerpt below), it is Applicant’s Formula 10a and a structure with a pyridazine skeleton are disclose as ligation units.
Scheme 4
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Mamat et al disclose that the chelator was radiolabeled and for pretargeting purposes, and an antibody was modified with azido functions in Scheme 18 and the paragraph appearing right before Scheme 18. Thus, it would have been obvious to a skilled artisan to substitute the highlighted ligation units from Scheme 4 into diagram of Scheme 3 and generate a radioactive metal labeled antibody modified with a peptide. Thus, the limitations of claim 11 are met.
Comments/Notes
For clarity of claim 11, one may want to delete ‘the following’ from claim 11, line 4.
The full scope of independent claim 11 was not searched.
Conclusion
Claim 11 is rejected and claims 1-10 and 12-15 are withdrawn.
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.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
July 26, 2025