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
Applicant’s election without traverse of claims 1-11 in the reply filed on 12/10/2025 is acknowledged.
Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/10/2025.
Claims 1-11 have been examined on the merits herein.
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.
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(s) 1-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over each of Kakino et al. (J. Ather. Thromb., vol. 26, p. 947-958, 2019, IDS), Kakino et al. (P1.008, 2018, IDS), JP6231307 (IDS) in view of Kakino et al. (Circ. J. vol. 80, p. 2541-2549, 2016, IDS) and Ye et al. (Biochim. Biophys, 2013) supported by Sawamura et al. (US20170015744, IDS).
Kakino (2019) teach a method for quantifying modified HDL comprising binding a modified HDL to a modified HDL-binding protein, i.e. a chimeric fusion protein comprising recombinant LOX-1 and anti-apoA1 antibody (p. 948, whole 2nd col.-p. 949, whole page, Generation of Chimeric fusion protein section, Fig. 1B, p. 951, Results section-p. 952, A chimeric protein standard section, Fig. 4).
Regarding claim 6, the binding protein is recombinant, i.e. recombinant LOX-1 and anti-apoA1 antibody (p. 948, Mat. & Meth. Section, Sandwich ELISA section).
Regarding claims 7-9, the quantification is performed by forming a complex of modified HDL and binding protein (LOX-1 and anti-apoA1) and quantified by ELISA immunoassay (p. 948, Mat. & Meth. Section, Sandwich ELISA section-p.949, whole page, Generation of chimeric fusion protein, Fig. 1).
Regarding claims 10 and 11, serum was used as the sample for quantification to which the binding protein is added (p. 950, Blood chem. Section, p. 952, A chimeric protein standard section).
Kakino teaches that both modified/dysfunctional LDL and HDL have proatherogenic properties which are mediated by LOX-1. Kakino teaches the quantification of both modified LDL and HDL by quantifying its LOX-1 binding activity using LOX-1 with anti-apoB (for LDL-termed LAB) and LOX-1 with apoA1 (for HDL-termed LAA) (p. 948, whole 2nd col.-p. 949, whole page, Fig. 1B). Kakino teach that the LAA method involves recognition epitopes of modified HDL by LOX-1 and allows the measurement of the activity of modified HDL’s via LOX-1 (p. 955, Advantages of the LAA methodology).
Kakino (2018) teach a method for quantifying modified HDL comprising binding a modified HDL to a modified HDL-binding protein, i.e. recombinant LOX-1 and anti-apoA1 antibody.
Regarding claim 6, the binding protein is recombinant, i.e. recombinant LOX-1 and anti-apoB antibody (see entire poster).
Regarding claims 7-9, the quantification is performed by forming a complex of modified HDL and binding protein (LOX-1 and anti-apoA1) and quantified by ELISA immunoassay (see entire poster).
Regarding claims 10 and 11, serum was used as the sample for quantification to which the binding protein is added (see entire poster).
JP6231307 teaches a method for quantifying modified/dysfunctional HDL in a sample and comprising binding modified HDL to a modified HDL binding protein, i.e. LOX-1 (0001, 0006-0008, 0015, 0016, 0018, 0059).
Regarding claim 6, the binding protein is recombinant, i.e. recombinant LOX-1 and anti-apoA1 antibody (0019, 0024, 0062).
Regarding claims 7-9, the quantification is performed by forming a complex of modified HDL and binding protein (LOX-1 and anti-apoA1) and quantified by ELISA immunoassay (0028, 0029, 0032, 0066, 0067).
Regarding claims 10 and 11, serum or plasma can be used as the sample for quantification to which the binding protein is added (0063).
The above references do not teach the modified HDL-binding protein to comprise a protein having a sequence of an L chain region of Factor V according to claims 1-5.
However, applicants disclosure teaches that in vivo modified HDL binds to LOX-1 via Factor V, specifically through its phoshatidylserine recognition site (0027). Additional support is provided by Sawamura et al. (US20170015744) who teach that LOX-1 binds to Factor V to form a complex (0018, 0034, for example).
Therefore, before the effective filing date of the claimed invention, LOX-1 intrinsically comprises a phospholipid recognition site of Factor V; however, it would be obvious to add an HDL modified binding protein having a sequence of Factor V or its phospholipid recognition site to the quantification methods of Kakino and JP307, with a reasonable expectation of successfully quantifying modified HDL because it was known before the effective filing date that modified HDL binds to LOX-1 via a phosphatidylserine recognition site of Factor V. Further, variants such as MFG-E8 having homology to C2 domains of Factor V and Factor VIII were known (see Ye et al., previously cited) and Del-1 having the phospholipid recognition site of Factor V was known and used by Kakino (2016, see intro., p. 2542, 1st full parag.) in lipoprotein quantification methods of Kakino (2019), specifically the LAB quantification method, where Del-1 is added to method (and binds to modified lipoproteins, p. 2547, Discussion section) and modified lipoproteins are quantified using ELISA (see Kakino 2016, p. 2542, Cell-free binding assay).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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/TIFFANY M GOUGH/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651