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 .
Claim Status
Applicant’s amendments and remarks, filed 12/23/2025, are acknowledged.
Claims 1-2, 5, 9, 12, 18-19, and 25-27 are canceled.
Claims 3, 6, 8, 10, and 21-22 are amended.
Claims 3-4, 6-8, 10-11, 13-17, and 20-24 are pending.
Claims 3-4, 6-8, 10-11, 17, and 21-22 are allowable. Claims 13-16, 20, and 23-24, previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement among inventions I-III, as set forth in the Office action mailed on 01/07/2025, is hereby withdrawn and claims 13-16, 20, and 23-24 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
As such, claims 3-4, 6-8, 10-11, 13-17, and 20-24 pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/23/2025 has been entered.
Withdrawn Objections
The claim objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the claims filed on 12/23/2025.
Withdrawn Rejections
Applicant’s arguments, see page 12, filed 12/23/2025, with respect to claim 6 rejected under 35 USC 112(d) as allegedly being of improper dependent form has been fully considered and are persuasive. The issue regarding improper dependent subject matter have been sufficiently addressed through amendments to the claim(s). As such, the rejection under 35 USC 112(d) is withdrawn.
Applicant’s arguments, see page 16, filed 12/23/2025, with respect to claim 21 rejected under 35 USC 112(b) as allegedly being indefinite has been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see page 16, filed 12/23/2025, with respect to claim 21 rejected under 35 USC 112(a) as allegedly lacking written description has been fully considered and are persuasive. The issue regarding the specification failing to disclose Applicant’s possession of antigen-binding fragments comprising only VH FRs or VL FRs have been sufficiently addressed through amendments to the claims. As such, the rejection under 35 USC 112(a) is withdrawn.
Applicant’s remarks, see page 16, filed 12/23/2025, with respect to claim 21 rejected under 35 USC 102 as allegedly anticipated by Luo et al (CA3001231 A1; publication date: 04/13/2017) has been fully considered and are persuasive. Further, Examiner acknowledges that claim 21 was amended to depend from claim 3 which comprises VH and VL CDR sequences which are not disclosed by the art. As such, the rejection of claim 21 under 35 USC 102 is withdrawn.
Applicant’s remarks, see page 16, filed 12/23/2025, with respect to claim 21 rejected under the non-statutory judicially-created doctrine of obviousness double patenting over claims 1-7, 9-10, and 15-17 of US Patent No. 10,689,434 has been fully considered and are persuasive. As such, the double patenting rejection is withdrawn.
Claim Interpretation
Examiner acknowledges that the term “prevention/preventing” refers to a method that is carried out in order to suppress or delay the occurrence of a disease, a disorder or a symptom (such as HBV infection or a disease associated with HBV infection) in a subject (see page 29).
Further, Examiner acknowledges that the term “treatment/treating” refers to a method that is carried out in order to obtain a beneficial or desired clinical outcome (see page 29).
Claim Rejections - 35 USC § 112(b)
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 20 and 23-24 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.
Claim 20 recites an “HBV infection-associated disease”. This renders the claim indefinite because the term “HBV infection-associated disease” is not defined by the claim, 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. One would not be apprised as to what is encompassed by the term and it is unclear if “associated” means directly linked to HBV infection, or indirectly occurred due to an HBV infection. As such claim 20 and its dependent claims are rejected.
Claim Rejections - 35 USC § 112(a) Scope of Enablement
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 20 and 23-24 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 treating HBV infection, does not reasonably provide enablement for treating any HBV infection-associated disease, or preventing an HBV infection or HBV infection-associated disease. 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 claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement
requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S.
261, 270 (1916) which postured the question: is the experimentation needed to practice the
invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858
F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does
not use the term "undue experimentation," it has been interpreted to require that the claimed
invention be enabled so that any person skilled in the art can make and use the invention without
undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence
to support a determination that a disclosure does not satisfy the enablement requirement and whether
any necessary experimentation is "undue." These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content
of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors most relevant for this rejection are: (A) the breadth of the claims; (B) the nature of the invention; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In regard to Wands factors (A) and (B), the breadth of the claims needed to enable the invention
is determined by whether the scope of enablement provided to one skilled in the art by the disclosure is
commensurate with the scope of protection sought in the claims. AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). The propriety of a rejection based upon the scope of a claim relative to the scope of the enablement concerns (1) how broad the claim is with respect to the disclosure and (2) whether one
skilled in the art could make and use the entire scope of the claimed invention without undue
experimentation.
The nature of the invention is a method for preventing or treating a hepatitis B virus (HBV) infection or HBV infection-associated disease in a subject, comprising: administering an effective amount of the antibody or antigen-binding fragment thereof according to claim 3 or a pharmaceutical composition comprising the antibody or antigen- binding fragment thereof, to the subject in need thereof. Therefore, the nature of the invention is a biochemical case, where there is natural unpredictability in performance of certain species other than those specifically enumerated; see MPEP § 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the functionality of the claimed method, with a reasonable expectation of success, because it would not be predictable from the disclosure of any one particular species may or may not work; see MPEP § 2164.03.
In regard to Wands factors (C), (D), and (E), the state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains and provides evidence for the degree of predictability in the art; see MPEP § 2164.05(a). The claims encompass treating any HBV associated infection-associated disease, including chronic HBV infection in a subject comprising administering the claimed antibody or antigen-binding fragment thereof.
The art teaches the unpredictability of antibody-based HBV immunotherapies. Gao et al (HUMAN VACCINES & IMMUNOTHERAPEUTICS 2017, VOL. 13, NO. 8, 1768–1773) teach that HBV is difficult to eliminate by available therapeutics as only a small fraction of patients (<10%) achieve HBsAg clearance (see pg. 1768). The two major reasons for this is due to the persistence of the intracellular HBV replication intermediate which resides in HBV-infected cells and cannot be suppressed by current treatments and the exhausted host anti-HBV immune response included in the functional exhaustion of either cellular or humoral antiviral immunity (see pg. 1768). Gao et al teach immunotherapy with HBsAg-specific antibodies has shown some direct HBsAg suppression effects in several preclinical and clinical trial studies; however, most described previously HBsAg-specific antibodies only had very short-term HBsAg suppression effects in chronic HBV infection (CHB) patients and animal models mimicking persistent HBV infection (see Abstract).
Further, Bertolitti and Le Bert (Gut and Liver, Vol. 12, No. 5, September 2018, pp. 497-507) disclose of the limitations of immunotherapies for CHB. In CHB patients, the quantity of circulating and intrahepatic HBV-specific T cells is not proportional to the level of biochemical activity (see pg. 503, left col.). Young CHB patients considered “immune tolerant” (low alanine aminotransferase (ALI) and very high levels of HBV DNA) have a repertoire and function of HBV-specific T cells that is similar to the one of the patients with chronic active hepatitis (high ALI levels and high HBV DNA); thus, the difference between chronic HBV patients with either low or high levels of ALI is their level of intrahepatic inflammatory cells (inflammatory monocytes, non HBV-specific T cells, NK cells) and not their level of HBV-specific immunity (see pg. 503, right col.). Importantly, basic immunological studies comparing immune profiles of humans at different ages have shown that pro-inflammatory responses increase proportionally with age (see pg. 503, right col.).
As such, the art discloses that there are several factors that impact the efficacy of immunotherapies when treating chronic HBV infection, and given the unpredictability of treating CHB using antibody therapy one of skill in the art could not predictably treat or prevent CHB comprising administering the claimed antibodies.
In regard to Wands factors (F), (G) and (H), the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech
Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The claims are drawn to a method for preventing or treating a hepatitis B virus (HBV) infection or HBV infection-associated disease in a subject, comprising: administering an effective amount of the antibody or antigen-binding fragment thereof according to claim 3 or a pharmaceutical composition comprising the antibody or antigen- binding fragment thereof, to the subject in need thereof.
The working examples provided by Applicant do not demonstrate a method of preventing or treating chronic HBV infection or any HBV infection-associated disease comprising administering the claimed antibody. Example 4 disclose of injecting HBV transgenic mice with the claimed antibodies to detect the concentrations of HBsAg , antibody and HBV DNA in serum, the antigen clearance rate and antibody half-life of the antibodies in vivo (see pgs. 46 and 47). The specification discloses that the antibody C26, comprising SEQ ID Nos: 3 and 4, had an antibody clearance ability stronger more than one order of magnitude than that of the positive (see FIG. 11B). Additionally, the specification teach that the antigen clearance ability of D3 (comprising SEQ ID Nos: 8 and 9), D4 (comprising SEQ ID Nos: 59 and 10), and D5 (comprising SEQ ID NOs: 59 and 9) was equivalent to that of C26, and the duration time was longer than that of C26 indicating that D3, D4, and D5 had a better function of circularly and reciprocally binding antigen (see FIG. 11C; pg. 48).
Because the specification only studied mouse models of HBV infection, one cannot assume that the method of treating or preventing a vast variety of HBV infection-associated diseases or chronic HBV infection will work similarly to the mouse models provided in the specification. In the absence of empirical determination, one skilled in the art would be subjected to undue experimentation to determine if the claimed method of treating or preventing any other type of HBV infection would result in therapeutic response as recited in the claims. Applicant is reminded that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. See Genentech, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. 112 first paragraph.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 15 and 16 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). Claims 15 and 16 recite the term “host cell”. The specification cites that the term refers to a cell into which a vector can be introduced, which includes, but is not limited to, prokaryotic cell such as Escherichia coli or Bacillus subtilis, fungal cell such as yeast cell or Aspergillus, insect cell such as S2 Drosophila cell or Sf9, or animal cell such as fibroblast, CHO cell, COS cell, NSO cell, HeLa cell, BHK cell, HEK 293 cell or human cell (see page 28). Because human cells are encompassed within the term, and the claims nor specification require that the host cell be isolated from the host, claims 15 and 16 are rejected as the claims encompass a human organism.
Allowable Subject Matter
The combination of CDR sequences as recited in claim 3 appear to be free of the art. The closest prior art is Luo et al (WO 2017/059813 A1; publication date: 04/13/2017) which disclose of an antibody, in particular a humanized antibody, to HBsAg (see Abstract). Specifically, Luo et al disclose of SEQ ID NO: 13 which shares 83.7% identity with instant SEQ ID Nos: 17, 12, and 13, and SEQ ID NO: 191 which shares 82% identity with instant SEQ ID Nos: 25, 15, and 23 (see alignments below).
SEQ ID NO: 13 Alignment
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262
698
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Greyscale
SEQ ID NO: 191 Alignment
PNG
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242
700
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Greyscale
Conclusion
Claims 3-4, 6-8, 10-11, 13-14, 17, and 21-22 are allowed.
Claims 15, 16, 20 and 23-24 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANAYA L MIDDLETON whose telephone number is (571)270-5479. The examiner can normally be reached M-F 9:30AM - 6PM with flex.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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