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
In response to the restriction requirement dated 4th June 2026, Applicant elects, without traverse: Group I, nuclide-labeled inhibitory peptide. Applicant’s election in the reply filed on 17th July 2026 is acknowledged.
Claim 1 is hereby examined on the merits. Claims 2-20 are withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
This application filed 11/16/2023 is a Continuation of PCT/CN2023/081067 , filed 03/13/2023
claims foreign priority to 202210578560.X, filed 05/26/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/23/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
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 1 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 1 recites the limitation ‘prepared by’ and is interpreted by the Examiner as a product-by-process claim. Here, it is unclear what the limitation ‘by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)’ means. In the way the claim is currently phrased, ‘by DOTA’ indicates that DOTA is used only to label ASF1a peptide with the nuclide and is not part of the nuclide-labeled inhibitory peptide. However, embodiments of the specification disclose DOTA coordinated to the nuclide and is part of the ASF1a peptide (see Fig 1). Since there is ambiguity in the claimed structure, the claim needs to be corrected to represent the structure that is claimed. For prior art purposes, Examiner interprets the structure to incorporate DOTA.
Claim 1 is directed to ‘an ASF1a peptide…DOTA’. The claim also recites ‘wherein an amino acid sequence of the ASF1a peptide…SEQ ID NO: 1’. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation ‘ASF1a peptide’, and the claim also recites ‘an amino acid sequence’ in lines 2 and 3. Here, it is unclear whether the claim is directed to a genus of ASF1a peptides or to any one of several ASF1a peptides, wherein one of the peptides is SEQ ID NO: 1 -which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For prior art purpose, Examiner interprets the ASIF1a peptide to be SEQ ID NO:1.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over May Bakail et al., hereinafter Bakail (May Bakail et al., Cell Chemical Biology 26, 2019, 1573–1585) in view of Sara Ahlgren et al., hereinafter Ahlgren (Sara Ahlgren et al., Bioconjugate Chem. 2008, 19, 235–243) in view of Ashok Chauhan et al., hereinafter Chauhan (Chauhan et al., J Control Release. 2007 February 12; 117(2): 148–162) evidenced by Frencesco Carderelli et al., hereinafter Carderelli (Francesco Carderelli et al., J Biol Chem. 2011 Feb 14;286(14):12292–12299).
Regarding claim 1, this is a product-by process claim. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP 2113 (I).
Bakail teaches peptides that inhibit the ASF1-histone interaction (see Summary, line 5). Specifically, Bakail teaches the peptide ip4 (see Supplementary Table S1) and peptide for cell penetration using the disclosed ip4 sequence (represented below from Bakail).
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Bakail teaches that to test biological activity of the ASF1 peptide inhibitors transduced in U2OS cell lines, the peptides are lengthened at their N terminus with a cell penetrating peptide sequence (CPP) (Figure 5A and Table S1) -the repeat tag sequence ‘‘RRPRRPRRPRRPRRP’’. Chauhan teaches CPPs for introducing recombinant proteins into the cells, e.g., Tat PTD (protein transduction domain) (see page 2, section 2, lines 1-2). Specifically, in Section 3, Chauhan teaches that analysis of Tat protein identifies a PTD of 9-11 aa residues, a basic domain that can transduce itself, as well as the bigger proteins fused with it, into the cells: as evidenced by Carderelli.
Bakail and Chauhan do not teach nuclide labelling by DOTA.
Ahlgren teaches radionuclide targeting of affibody molecules, and the introduction of a single thiol group engineered into the protein by introduction of one cysteine (see Abstract line 4). Ahlgren discloses that MMA-DOTA for 111In-labelling of anti-HER2 affibody molecules comprising introducing a Cys residue (see Abstract). Notably, Ahlgren discloses the clinical utility of the tracer in SPECT and PET, following labelling with 111In or 68Ga respectively (see page 236, last line of paragraph 1). The absence of cysteines in the Affibody molecule provides the possibility to obtain a unique attachment site by introduction of a single cysteine, e.g., as a C-terminal residue. The use of a bifunctional chelator, linker molecule, or other reporter with a thiol-reactive moiety, e.g., maleimide or iodoacetamide, enables directed conjugation with this particular cysteine. This has been used previously for coupling of, e.g., Oregon Green 488 or horseradish peroxidase (HRP) to the dimeric Affibody molecule (ZHER2:477)2-Cys (15) for in vitro detection of HER2 (page 236, 2nd paragraph). Ahlgren discloses that advantage of a DOTA-containing conjugate has the potential for labeling with positron-emitting generator-produced 68Ga (T1/2 ) 68 min) (see page 242, Col1 last few lines).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re
Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ip4 cell penetrating peptide of Bakail and substitute the CPP with the HIV TAT peptide as suggested in Chauhan. Since DOTA labelling of 68Ga as disclosed in Ahlgren for site-specific labelling requires a single C-terminal Cysteine residue, it is reasonable to introduce a Cysteine residue, at the end of the HIV TAT peptide.
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Instantly claimed peptide is shown below:
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One motivated to do so would have a reasonable expectation of success as the ip4 sequence linked to a CPP is disclosed in Bakail and 68Ga nuclide labeling of proteins using DOTA by introducing a C-terminal Cysteine is disclosed in Ahlgren. Thus, one would have recognized that applying the teaching of Bakail, Chauhan and Ahlgren, would have yielded predictable results in generating an ASF1-histone interaction inhibitory peptide, labelled with 68Ga nuclide using DOTA, for radiopharmaceutical distribution and imaging (See MPEP § 2143 l(A)(D)).
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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