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 .
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.
Formal Matters
The examiner for this office action has been changed to Gregory S. Emch, Supervisory Patent Examiner, Art Unit 1678.
The reply filed on 05 June 2025 has been received and entered in full. Claims 20-28 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05 June 2025 has been considered by the examiner.
Withdrawn Objection/Rejection
The objection to the specification is hereby withdrawn.
The rejection of claims 20-28 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-18 of U. S. Patent No. 10,401,371 has been withdrawn in response to the terminal disclaimer filed and approved on 05 June 2025.
Maintained Rejection
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 20-28 are rejected under 35 U.S.C. 103 as being unpatentable Fitzpatrick et al. (US 2003/0003501, IDS Reference) in view of Ohno-Iwashita et al. (Cholesterol binding and cholesterol transport proteins, Subcellular Biochemistry 51, 2010, chapter 22 pages 597-621).
The claims are drawn to a kit for measuring cholesterol level in blood comprising CDC (Cholesterol Dependent Cytolysin) as a cholesterol binding protein and an anti-apolipoprotein antibody, wherein the anti-apolipoprotein antibody is fixed on a solid support and the CDC is labelled with a detectable material.
Fitzpatrick et al. teach throughout the patent and especially in Abstract, reagents for the determination of lipoproteins shown to correlate with HDL and LDL, wherein the reagents are in kits (claims 12-19;[0005]) for the determination of HDL, LDL [0015] [0018] wherein the kit comprises anti-apolipoprotein antibodies including anti-apolipoprotein B-100 antibody i.e. anti LDL antibody [0031]-[0034], and -apolipoprotein A-1 antibody i.e. anti HDL antibody [0035]-[0038](instant claims 21-22). Fitzpatrick et al teach antibodies can be monoclonal or polyclonal and can be immobilized to a solid phase material for the detection of cholesterol HDL,LDL or respective apoproteins bound to the cholesterol molecules[0060], in sandwich immunoassays [0057]-[0059] in various formats as for example dipsticks or ELISA [0060] or immunoturbinometric sandwich assays wherein the solid support is for example nitrocellulose or microwells [0060] (instant claims 25-28).
Fitzpatrick et al. is silent regarding the kit comprising CDC (Cholesterol Dependent Cytolysin) as a probe for cholesterol.
Nevertheless, CDC’s are known as probes that have specificity for cholesterol as taught in Ohno-Iwashita et al.
In particular, Ohno-Iwashita et al. teach throughout the publication and especially in Abstract, cholesterol binding probes include antibodies and cholesterol-dependent cytolysins (CDC) as for example PFO (Perfringolysin O)(page 598;page 599 1st and 2nd paragraphs) ) (instant claims 23-24) wherein the cholesterol-dependent cytolysins is conjugated with fluorescent dyes (page 609, 1st paragraph; page 615, lest paragraph)
However, it would have been prima facie obvious, before the effective filing of the claimed invention, to include labeled cholesterol-dependent cytolysins (CDC) taught in Ohno-Iwashita et al. as binding probes for cholesterol in the kit comprising comprises anti-apolipoprotein antibodies of Fitzpatrick et al. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP § 2144.06. One of ordinary skill would have had the motivation to include probes for binding cholesterol comprising CDC and anti-apolipoprotein antibodies for the measurement of LDL or HDL cholesterol in a kit for a thorough evaluation and for comparison. It would have been with predictable expectation of success that CDC and antibodies for apoproteins would bind cholesterol wherein the anti-apolipoprotein antibody is fixed on a solid support and the CDC is labelled with a detectable material as Ohno-Iwashita et al. teach CDC probes specifically bind cholesterol to allow for measurement of cholesterol in sandwich assays for increased sensitivity and for comparison.
The claimed CDC appear to be the same as the prior art product absent a showing of unapparent differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA).
Response to Arguments
Applicant's arguments filed 05 June 2025 have been fully considered but they are not persuasive. Applicant asserts that the purpose of the claimed invention is to provide a kit for measuring cholesterol level in blood, not individual CDC or antibody. Applicant asserts that the Fitzpatrick method, by utilizing anti-apolipoprotein antibodies, measures not only cholesterol particles in the blood but also free apolipoproteins in the blood that do not contain cholesterol. Thus, applicant alleges that it cannot accurately quantify human blood cholesterol concentration and that Fitzpatrick provides no motivation to arrive at a kit for measuring blood cholesterol utilizing CDC in addition to anti-apolipoprotein antibodies.
This is not found persuasive as the claims do not exclude a kit that can also measure free apolipoproteins in the blood that do not contain cholesterol. The claims merely require a kit for measuring cholesterol level in blood comprising CDC (Cholesterol Dependent Cytolysin) as a cholesterol binding protein and an anti-apolipoprotein antibody, wherein the anti-apolipoprotein antibody is fixed on a solid support and the CDC is labelled with a detectable material.
The intended use “for measuring cholesterol level in blood” is recited in the preamble of the claimed kit. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim (see MPEP § 2111.02, II). According to the claims, a kit for measuring cholesterol level in blood merely requires CDC and any anti-apolipoprotein antibody fixed to a solid support. This reads on the anti-lipoprotein antibody of Fitzpatrick. There is nothing in the claims that requires that the anti-lipoprotein antibody does not bind to free apolipoproteins in the blood that do not contain cholesterol. Thus, the claimed antibody would similarly bind to free apolipoproteins in the blood that do not contain cholesterol. If applicant intends the antibody of the claims to function differently than Fitzpatrick’s antibody, the claims should be amended to require the structure necessary to distinguish the antibody of the claims from Fitzpatrick’s antibody. As currently drafted, the anti-apolipoprotein of the claims requires no more than what is taught in Fitzpatrick. As Fitzpatrick teaches an anti-apolipoprotein antibody and teaches that it can be used to quantify cholesterol levels in antibody-antigen binding techniques (see, e.g., [0059]), the assertion that Fitzpatrick provides no motivation whatsoever to arrive at the claimed kit cannot is incorrect.
Applicant asserts that the anti-cholesterol antibody of Ohno-Iwashita merely targets cholesterol and is different from the anti-apolipoprotein of the claims, which targets apolipoprotein (membrane protein) present in LDL, HDL, and the like. Applicant asserts that Ohno-Iwashita does not teach or suggest a method of measuring the cholesterol level in blood using an anti-apolipoprotein antibody. Applicant alleges that neither reference provides motivation to combine anti-apolipoprotein antibodies and CDC to determine the cholesterol level in human blood.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is not necessary that Ohno-Iwashita teach an anti-apolipoprotein antibody as Fitzpatrick provides this embodiment. Regarding the allegation that there is no motivation to combine the two references and arrive at the claimed invention, both of the references teach quantifying cholesterol with CDC and anti-apolipoprotein antibodies. As set forth above, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP § 2144.06. This same portion of the MPEP discusses substitution of equivalent elements, and states that an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In reFout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Applicant asserts that one of ordinary skill in the art would not have been motivated to arrive at the claimed invention based on common knowledge in the art. Applicant alleges that Reference 1 (Mallick et al.) and Reference 2 (Kim), both cited on the IDS filed 05 June 2025, support that conventional immunological methods previously attempted to target only apolipoproteins present in lipoprotein particles but that the apolipoprotein concentrations measured did not correlate well with HDL or LDL cholesterol concentrations, rendering them unsuitable for practical product use. See Reference 1, Figures 2 & 3; and Reference 2, Fig. 6.
Applicant’s assertions regarding Figures 2 & 3 of Reference 1 are inaccurate. Reference 1 explicitly states, “As expected our study showed significant relation between apolipoproteins and their corresponding lipoproteins (Figure 2 and 3)”. See p.380, para. under “RESULTS”. For each of these Figures, the correlation was highly significant with p<0.001. See p.382.
Similarly, in Reference 2 regarding Figure 6, it is stated, “Therefore, this result suggested that the fluorescence immunochromatographic assay system for LDL cholesterol (low density lipoprotein) gave a confident performance compared to other well-known assay system”. See p. 22, Fig. 6 legend. Thus, both Reference 1 and Reference 2 demonstrate the exact opposite of what applicant alleges.
Conclusion
No claim is allowed.
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 GREGORY S EMCH whose telephone number is (571)272-8149. The examiner can normally be reached Monday - Friday, 7:30 am - 3:30 pm PT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Mallari can be reached at (571)272-4729. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
/PATRICIA MALLARI/Director, Technology Center 1600