DETAILED ACTION
Election/Restrictions
Applicant’s election of Group II, claims 5-8, in the reply filed on March 18, 2026 is acknowledged. Because Applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Priority
Acknowledgment is made of applicant's claim for foreign priority based on applications CN2022100273107, CN202111212401, and CN2021106138706, all filed in China on June 2, 2021. It is noted, however, that Applicant has not filed a certified copy of CN2022100273107 or CN202111212401 as required by 37 CFR 1.55.
Claims Summary
Claim 5 is directed to a method for detecting immune capture molecules which are complete HBV virus particles. The method comprises:
Antibody-magnetic bead coupling, wherein the antibody is a PreS1 antibody or an HBc antibody;
HBV virus particle capture; and
Real-time fluorescence qPCR
Claims 5 and 6 outline the steps for antibody-magnetic bead coupling, including mixing the following in a buffer to activate the beads: carboxy magnetic beads, and equal amounts of an NHS solution and an EDC. Then, mixing and reacting the activated beads with an antibody to be coupled in a coupling buffer, thus obtaining an antibody-magnetic bead coupling reaction product. More detailed steps are outlined in claim 6.
Claim 7 outlines the steps of the HBV particle capture process, comprising magnetic separation to discard a supernatant of the antibody-coupled magnetic bead preservation solution, washing, mixing with a diluted cell supernatant or serum of an HBV patient, wherein the antibody-coupled magnetic beads capture the HBV particles in the diluted patient sample. More details are outlined in claim 7. Claim 8 outlines the steps of the RT-qPCR.
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 6-8 are 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.
The term “vigorously” and “quickly” in claim 6, and thus dependent claims 7-8, are relative terms which render the claims indefinite. The terms are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 8 recites “required reagents” and “standards A-D” without identifying what the reagents are or what they are for exactly. The specification does not provide any further detail.
Claim 8 recites the limitation "per person", which appears to be referencing “a hepatitis B patient” in claim 7. However, consistent terminology should be used if that is the case. There is insufficient antecedent basis for this limitation in the claim.
The metes and bounds of the claims cannot be determined without further clarification.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for detecting complete HBV particles when using a PreS1 antibody, does not reasonably provide enablement for a method for detecting complete HBV particles when using an HBc antibody. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The breadth of the claims encompasses the detection of whole virions (complete HBV) using a method involving antibodies to PreS1, or antibodies to HBc. The nature of the invention is the detection of whole HBV (as stated in claim 5) by capturing whole HBV and performing RT-qPCR to confirm the presence of HBV. Notably, the instant specification at paragraph [0086] of the published application (US 2024/0018611) teaches that PreS1 is a unique structure to HBV Dane (or complete HBV particles), thus antibodies to PreS1 will bind to whole virions. Antibodies that bind to HBc are not binding to whole virions since core antigen is inside the outer surface antigen structure. This understanding is confirmed in paragraph [0086] which discusses differential detection with antibodies that bind PreS1 and antibodies that bind HBc.
Therefore, in view of the breadth of the claims, the nature of the invention, the explicit teachings of the specification, and the low level of predictability of binding whole HBV with anti-HBc antibodies, it would require undue experimentation to practice the claimed method. Amendment of the claims to require the use of the PreS1 antibody (as opposed to its recitation as an alternative in claim 5) would overcome this 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.
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 5 is rejected under 35 U.S.C. 103 as being unpatentable over Gandhi et al. (Transfusion, August 2000, 40:910-916, “Gandhi”) in view of Gu et al. (CN 104914243 A, published 9/16/2015, English translation provided, 15 pages, “Gu”) and Grace Adams (Biochem (Lond), June 15, 2020, 42(3):48-53, “Adams”).
Gandhi’s teachings are directed to HBV virion isolation using antibodies to pre-S1 (see title). Gandhi discloses isolation of HBV DNA from viremic plasma using immunoaffinity capture of intact HBV using streptavidin-coated magnetic beads coupled to biotinylated pre-S1 antibodies, and subsequent heminested PCR analysis (see page 910, left column, “Study Design and Methods” section).
Gandhi does not disclose carboxy magnetic beads, however, it would have been an obvious alternative to Gandhi’s streptavidin-coated beads. Gu discloses magnetic beads having carboxyl groups for attaching HBV pre-S1 antibodies in a method of detecting pre-S1 antigen (see abstract). The antibody-magnetic beads are prepared by mixing the beads with equal parts of NHS and EDC in a buffer, and then mixing with pre-S1 antibody in a coupling buffer solution (see pages 3 and 5 of Gu). Since Gandhi’s streptavidin-coated beads and Gu’s carboxy beads both bind pre-S1 antibodies, they are art-recognized equivalents for the same purpose: complexes of antibody-magnetic beads that bind to HBV pre-S1.
Gandhi’s method uses heminested PCR, not suggest real-time fluorescent qPCR. However, it would have been obvious to have used real-time fluorescent qPCR with a reasonable expectation of success, motivated by advantages over PCR such as visualization of reactions in real time, and copy numbers of detected sequences (see Adams, page 48, right column, “Overview of qPCR and RT-qPCR”).
Conclusion
No claim is allowed.
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/STACY B CHEN/Primary Examiner, Art Unit 1672
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