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 with traverse of invention I in the reply filed on 7/15/25 is acknowledged. The traversal is on the ground(s) that there would not be an undue burden on examining both inventions. This is not found persuasive because undue burden is not factor considered in a lack of unity analysis.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9 and 10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/15/25.
Claims 1-8 and 11-17 are examined on the merits. Claims 11-17 are newly presented.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Amendment
The declaration under 37 CFR 1.132 filed 1/29/26 is insufficient to overcome the rejection of claims 1-8 based upon 35 USC 112(a) written description and scope of enablement as set forth in the last Office action because: the declaration provides detailed information related to monoclonal antibody technology. For example, co-inventor Ohue discusses how two hydridomas (HB124 and HB135 were generated and discussed in instant application. These hybridomas were capable of producing monoclonal antibodies that were capable of binding to a core antigen of an HBV genotype D virus. In this declaration, 5 additional hybridomas are also discussed (HB2-122, HB2-126, HB2-128, HB2-131 and HB2-132), which were created by applicant prior to the filing date of the instant application, but were not studied until after the filing date. The monoclonal antibodies produced by hybridomas HB2-122 and HB2-128 were identified to be similarly reactive to monoclonal antibody HB124 and HB135 with the core antigen of HBV genotype D at the epitope of amino acid residues 31 to 48 of SEQ ID NO: 3.
However, the rejections raised focus on whether applicants have described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, the inventor(s), at the time the application was filed, had possession of the claimed invention [Lacking Written Description]; and whether the specification enables 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 [Lacking Enablement]. At the time of filing instant application discloses two monoclonal antibodies (hybridomas HB124 and HB135) that applicants reduced to practice which bound to amino acid positions 31 to 48 of SEQ ID NO: 3. Therefore, the antibodies produced by hybridomas HB2-122, HB2-126, HB2-128, HB2-131 and HB2-132, which applicants did not disclose when the instant application was originally filed are interpreted to constituted information that would be new matter to the instant application. Therefore, information related to these antibodies is not persuasive to overcome the pending rejections herein. In summary, this disclosure does not establish that applicants have described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, the inventor(s), at the time the application was filed, had possession of the claimed invention [Lacking Written Description]; and whether the specification enables 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 [Lacking Enablement].
Claim Rejections - 35 USC § 112
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.
(Prior Rejection Maintained) Claims 1-8 and 11-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1-8 and 11-17 are rejected as lacking adequate descriptive support for a possession of a method of immunoassay of hepatitis B virus core antigen, the method comprising using, a monoclonal antibody that specifically binds to at least one kind of core antigen of hepatitis B virus genotype D or C or E or F, or an antigen-binding fragment thereof, wherein an epitope of the monoclonal antibody or the antigen-binding fragment thereof is a region included in the amino acid sequence from position 31 to 48 of SEQ ID NO:3.
The method also comprises determining if said monoclonal antibody specifically binds to said region included in the amino acid sequence from position 31 to 48 of SEQ ID NO:3. The antibody is produced by a hybridoma by recovering antibody producing cells of mice and fusing them with cell lines of a different animal, the monoclonal antibody is an IgG antibody, such as IgG2b, k or IgG2a, k.
In support of the claimed genus of an “using a monoclonal antibody that specifically binds to at least one kind of core antigen of hepatitis B virus genotype D or C or E or F, or an antigen-binding fragment thereof, wherein an epitope of the monoclonal antibody or the antigen-binding fragment thereof is a region included in the amino acid sequence from position 31 to 48 of SEQ ID NO:3.” The specification discloses two monoclonal antibodies specific for hepatitis B virus Core antigen of a genotype D. These antibodies are produced by hybridomas HB124 and HB135. No additional antibodies, derivatives or variants or mutants thereof are disclosed that can achieve the claimed ability to binding of a core antigen of a hepatitis B virus genotype D or C or E or F. Thus, other than the monoclonal antibodies produced by hybridomas HB44 and HB124, the application fails to provide a representative number of species within the claimed genus.
Moreover, the decision arrived at in Amgen v. Sanofi, 598 US 594 (2023) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed method using a generic monoclonal antibody or antigen binding fragment thereof that specifically binds to at least one kind of a core antigen of a HBV genotype D or C or E or F. The epitope of the monoclonal antibody or antigen binding fragment thereof is a region included in the amino acid sequence from positions 31 to 48 of SEQ ID NO: 3. Therefore, the monoclonal antibody or antigen binding fragment thereof is only defined by functional properties but no specific structure is recited by the claims. In view of the fact patterns detailed in Amgen v. Sanofi, applicants are in possession of a method of using the monoclonal antibodies that are produced by the hybridomas HB124 and HB135, which specifically bind to the core protein of HBV genotype D.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
(Prior Rejection Maintained and extended to new claims 11-17) Claims 1-8 and 11-17 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 using antibodies produced by hybridomas HB124 and HB135 to detect hepatitis B virus Core protein of genotype D by binding the epitope within the amino acid range of positions 31 to 48 of SEQ ID NO: 3, does not reasonably provide enablement for using antibodies or antigen binding fragments thereof that bind to a kind of core antigen of hepatitis B virus Core protein of genotype D. 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 legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to a method of immunoassay of hepatitis B virus core antigen, the method comprising using, a monoclonal antibody that specifically binds to at least one kind of core antigen of hepatitis B virus genotype D, or an antigen-binding fragment thereof, wherein an epitope of the monoclonal antibody or the antigen-binding fragment thereof is a region included in the amino acid sequence from position 31 to 48 of SEQ ID NO:3. The claimed region of positions 31 to 48 of SEQ ID NO: 3 is found in the core protein of HBV.
Working examples. A working example was provided in which a monoclonal antibody produced by hybridomas HB124 and HB135 were able to detect HBV core antigen of a genotype D virus. Another working example utilizing monoclonal antibodies produced by hybridomas HB44, HB61, HB114, HB124 and HB135 were also tested for detecting HBV Core protein, HBV E protein and pp22crAg.
Amount of experimentation necessary. Additional research is required in order to determine how effective how a generic monoclonal antibody or antigen binding fragment thereof can be used to specifically bind to a kind of core antigen or a HBV of genotype D, wherein the epitope that is bound is found within positions 31 to 48 of SEQ ID NO: 3.
Furthermore, in light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Applicants state that no undue experimentation would be necessary to arrive at the instant invention, which is supported by recent PTAB cases decided after the Amgen I and Amgen II decisions. In addition, the technology or arriving at therapeutic antibodies has not been studied for nearly as long as that if diagnostic antibodies, which the instant invention is drawn to. Therefore, diagnostics are more enabled than therapeutic antibodies, appears to be the argument that applicants are raising.
In response, the decisions from Amgen I and Amgen II make no distinction between a diagnostic antibody being more enabled than a therapeutic antibody. The focus of these decisions was to whether the patentee has enabled one of ordinary skill in the art to make or use an antibody and if the patentee was in possession of an antibody by only claiming what it can bind. Amgen provided examples of individual antibodies, but they were not representative of the larger genus. In comparison, applicants have reduced to practice 2 antibodies that can bind to the core antigen at an epitope formed by amino acids 31-48 of SEQ ID NO: 3 of a HBV genotype D virus, which isn’t representative of the claimed genus. In addition, the prior art does not teach antibodies capable of binding to this epitope. As stated above and in the previous Office action, in Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. With only two antibodies provided by applicants, the scope of this range of antibodies is not enabled and applicants are not in possession of the claimed genus of antibodies.
As stated above, the rejections raised focus on whether applicants have described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, the inventor(s), at the time the application was filed, had possession of the claimed invention [Lacking Written Description]; and whether the specification enables 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 [Lacking Enablement]. The 37 CFR 1.132 Declaration filed on 1/29/26 has failed to overcome these rejections. At the time of filing instant application discloses two monoclonal antibodies (hybridomas HB124 and HB135) that applicants reduced to practice which bound to amino acid positions 31 to 48 of SEQ ID NO: 3. Therefore, the antibodies produced by hybridomas HB2-122, HB2-126, HB2-128, HB2-131 and HB2-132, which applicants did not disclose when the instant application was originally filed are interpreted to constituted information that would be new matter to the instant application. Therefore, information related to these antibodies is not persuasive to overcome the pending rejections herein.
The rejections are maintained for reasons of record and as stated above.
(New Rejection Necessitated by Amendments) Claims 13 and 15 and 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 13 recites the limitation "antibody producing cells" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "said animal" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 13 recites the limitation "said cell line" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "antibody producing cells" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said animal" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 recites the limitation "said cell line" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/ Primary Examiner, Art Unit 1671