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 .
DETAILED ACTION
The amendment filed 11/06/2025 has been entered. Claims 1-11 are pending. Claims 5-11 are withdrawn. Claims 1-4 are pending and under examination.
Response to Arguments
Applicant's arguments filed 11/06/2025 have been fully considered but they are not persuasive. Applicant argues that Wagner and Stoffel fail to teach a binding domain of a first alpha-helical protein and at least a portion of a second alpha-helical protein.
However, Stoffel teaches a fusion protein comprising apolipoprotein A1 and apolipoprotein M (Page 8, lines 4-9), which are amphipathic alpha-helical proteins. Stoffel teaches that SEQ ID NO:1 represents the amino acid sequence of human apoM lacking the N-terminal 27 amino acids while SEQ ID NO:7 represents the amino acid sequence of human apoM lacking the N-terminal 19 amino acids (p. 5, lines 30-32). Stoffel teaches that the apoM/apoA1 fusion protein may comprise the amino acids of SEQ ID NO:1 or 7 and the N-terminal 26 or 25 amino acids of apoA1 (p 8, lines 4-6). Sphingosine-1-phosphate binds apoM at residues 98, 100, 116, 136, 102, 143, as evidenced by Zhang (p. 2, para. 2). Therefore, the fusion protein of Stoffel is considered to contain a binding domain of apoprotein M and a portion of apolipoprotein A. The rejection under 35 U.S.C. 103 is maintained.
Claim Rejections - 35 USC § 103
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 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Wagner et al. (WO 2018/017442 A1), previously cited, in view of Stoffel (WO 2009/056330 A1), previously cited, as evidenced by Zhang et al., (Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening. SCIENTIFIC REPORTS. 2016. 6:30655).
Regarding claim 1, Wagner teaches nanodisc embodiments and/or structures (para. [00140]). Wagner teaches that the term “conventional nanodisc” refers to a discoidal phospholipid bilayer encompassed by a membrane scaffold protein (MSP) e.g., two molecules of an amphipathic alpha-helical protein wrapped around the perimeter of the disc in an anti-parallel fashion (para. [00143]). Wagner teaches that the membrane scaffold protein may be an apolipoprotein (para. [00143]).
Wagner does not teach that the amphipathic alpha-helical proteins comprise a binding domain of a first alpha-helical protein and at least a portion of a second alpha-helical protein, i.e., Wagner does not teach that the amphipathic alpha-helical proteins are fusion proteins.
However, Stoffel teaches a chimeric polypeptide comprising two different apolipoproteins: apolipoprotein A1 and apolipoprotein M (Page 8, lines 4-9), which are amphipathic alpha-helical proteins. Stoffel teaches that SEQ ID NO:1 represents the amino acid sequence of human apoM lacking the N-terminal 27 amino acids while SEQ ID NO:7 represents the amino acid sequence of human apoM lacking the N-terminal 19 amino acids (p. 5, lines 30-32). Stoffel teaches that the apoM/apoA1 fusion protein comprises the amino acids of SEQ ID NO:1 or 7 and the N-terminal 26 or 25 amino acids of apoA1 (p 8, lines 4-6). Sphingosine-1-phosphate binds apoM at residues 98, 100, 116, 136, 102, 143, as evidenced by Zhang (p. 2, para. 2). Therefore, the fusion protein of Stoffel is considered to contain a binding domain of apoprotein M and a portion of apolipoprotein A.
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have substituted the apoA1/apoM fusion protein taught by Stoffel for the apolipoproteins in the membrane scaffold protein of Wagner. One of ordinary skill in the art would have been motivated to do so because Wagner teaches that the membrane scaffold protein may be an apolipoprotein (para. [00143]). One of ordinary skill in the art would have had a reasonable expectation of success because Wagner and Stoffel are in the same field of endeavor of apolipoprotein therapeutics.
Regarding claims 2 and 3, Stoffel teaches a chimeric protein comprising portions of both apoA1 and apoM (Page 8, lines 4-9).
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Regarding claim 4, because of the term “an amino acid sequence”, any amino acid sequence that shares at least 3 contiguous amino acids with SEQ ID NO:1 is considered to read on the claim. Stoffel teaches a fusion protein comprising portions of apoA1 and apoM (Page 8, lines 4-9), which has an amino acid sequence shown in SEQ ID NO:3 (Page 8, lines 18-22). SEQ ID NO:3 of Stoffel shares 51.8% sequence identity with a portion or variant of the instant SEQ ID NO:1 (see alignment below).
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657