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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/EP2021/080219 filed 10/29/2021, which claims the benefit of the priority of European Patent Application No. EP 20204915.1 filed 10/30/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 09/08/2023 have been considered by the examiner.
Election/Restrictions
Claims 3, 4-5, 8, 10-11, and 13 are withdrawn from further consideration pursuant to 37 CFR1.142(b) as being drawn to a nonelected Group II and III or based on the elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/12/2026. Applicant’s election without traverse of Group I drawn to a method for site-selective modification, in the reply filed on 01/12/2026 is acknowledged.
Applicant further elects the species of acylation tag HHHKHHHHHH, the acylating reagent
4-methoxylphenyl-2-azidoacetate. As a result, claims 3, 4-5, 8 are withdrawn.
Claim Status
Claims 1-11, 13 and 13 are pending. Claims 3, 4-5, 8, 10-11, and 13 are withdrawn. Claims 1-2, 6-7, and 9 are being examined on the merits in this office action.
Claim Objections
Claim 1 is objected to because of the following informalities: claim recites a. and b. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995); See also MPEP § 608.01(m).
Claim 9 recites formula (VI) or (V). the claim should me amended to recite “…formula (IV) or (V)...” because the instant specification discloses that the two compounds are formula (IV) or (V).
Applicant can amend the claim to recite a) and b). Appropriate correction is required.
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.
Claims 7 and 9 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 7 depends on claim 6 and recites the limitation “….analytical agent (B)…” in line 2. There is insufficient antecedent basis for this limitation in the claim. Its unclear if (B) represents the analytical agent or not. It is also unclear whether the limitations in the parenthesis are a required part of the claimed invention.
Regarding claim 9, the phrase "for example" or “e.g.” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The claim also contain a parenthesis. It is unclear whether the limitations in the parenthesis are a required part of the claimed invention.
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.
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 1-2, 6-7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Usera et al. (WO2015200080A1 – hereinafter “Usera”), in view of Tavare et al. (J. of Inorg. Biochem. 114 (2012) 24–27) and Maldonado et al. (Nat. Commun. 2018, 7; 9(1):3307).
Usera teaches a method for modifying a target protein or a target peptide comprising contacting the protein with an acylating compound, wherein the compound comprises histidine (Pages 1-3, 18). Usera teaches that the histidine tag comprises 1 to 10 histidine (page 19, 1st paragraph).
Usera does not teach that the acylation tag has a single lysine or that the acylation tag is HHHKHHHHHH, and that the acylating reagent is 4-methoxylphenyl-2-azidoacetate.
Examiner notes that the use of acylation tags that comprises lysine and at least three histidine residues is known in the art and the use acylating reagents such as 4-methoxylphenyl-2-azidoacetate is known in the art as taught by Tavare and Maldonado.
Tavare teaches site specific modification using a histidine tag, wherein the histidine tag is located in the C-terminus of the protein (Abstract), wherein the histidine tag includes peptides such as CKLAAALEHHHHHH (Abstract). Examiner notes that the tag of Tavare comprises a single lysine and at least 3 histidine residues.
Regarding the acylation reagent, Maldonado teaches a method of selective acylation of proteins or peptides and that the acylation tag had a Lys was placed C-terminal of the GHHHHHH and that the modification is at the neighboring Lys Nε-amine (Page 4, left col., line 1-7). Maldonado teaches the use of acylating reagent 4-methoxyphenyl 2-azidoacetate (18), and that the reagent is stable and could introduce with high selectivity an azido moiety at 4 °C which was particularly attractive feature (Page 8, right col., line 1-5, Page 9, right col., 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Usera with the teachings of Tavare and Maldonado and use the acylating tag taught by Tavare and Maldonado since Maldonado teaches that the tag with a lysine residue gave slightly elevated level of acylation (Page 4, left col. Line 1-4), and that the acylating reagent 4-methoxyphenyl 2-azidoacetate is stable and could introduce with high selectivity an azido moiety at 4 °C which was particularly attractive feature (Page 8, right col., line 1-5, Page 9, right col., 2nd paragraph). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the acylating tag and reagent taught by Tavare and Maldonado since Maldonado teaches using the acylating reagent 4-methoxyphenyl 2-azidoacetate introduces high selectivity azido moiety at 4 °C which was particularly attractive feature (Page 8, right col., line 1-5, Page 9, right col., 2nd paragraph). Examiner notes that the disclosures render obvious claim 1.
Regarding claim 2, Maldonado teaches a method of selective acylation of proteins or peptides and that the acylation tag had a Lys was placed C-terminal of the GHHHHHH and that the modification is at the neighboring Lys Nε-amine (Page 4, left col., line 1-7) which is less than 25 amino acids. Further, Tavare teaches wherein the histidine tag includes peptides such as CKLAAALEHHHHHH (Abstract). It would have been obvious to one of ordinary skill in the art to modify the method taught by Usera with the teachings of Tavare and Maldonado and use the acylating tag taught by Tavare and Maldonado since Maldonado teaches that the tag with a lysine residue gave slightly elevated level of acylation (Page 4, left col. Line 1-4),
Regarding claims 6-7, Maldonado teaches that the method comprises introducing biotin or fluorophore to aid in identification and characterization (Abstract; Page 4, left col., 2nd paragraph; Page 5, left col., last line). It would have been obvious to attach a bio interactive agent such as biotin and fluorophore to aid in identification and characterization of the protein.
Regarding claim 9, Maldonado teaches the use of acylating reagent 4-methoxyphenyl 2-azidoacetate (18), and that the reagent is stable and could introduce with high selectivity an azido moiety at 4 °C which was particularly attractive feature (Page 8, right col., line 1-5, Page 9, right col., 2nd paragraph). Maldonado teaches that the acylating reagent 4-methoxyphenyl 2-azidoacetate (18), has the structure
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which reads on claim 9, wherein R2 is methoxy, and E2 is an azide. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the acylating tag and reagent taught by Maldonado since Maldonado teaches using the acylating reagent 4-methoxyphenyl 2-azidoacetate introduces high selectivity azido moiety at 4 °C which was particularly attractive feature (Page 8, right col., line 1-5, Page 9, right col., 2nd paragraph).
EXAMINER’S COMMENT
Examiner notes that the instant method wherein the acylation tag is HHHKHHHHHH is free of prior art. The search was expanded to the genus and the rejection is disclosed above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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/MERCY H SABILA/Examiner, Art Unit 1654