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 invention I in the reply filed on 6/12/25 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Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6/12/2025.
Claims 1-7 are examined on the merits.
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.
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 1-7 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 testing the ability of a hepatitis B virus with a core protein that possesses mutations a positions 141, 143, 146 and 147 and how these mutations increase the amount of cccDNA inside a cell’s nucleus, does not reasonably provide enablement for testing for agents that inhibit HBV cccDNA and therefore HBV infections in an individual. 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.
Nature of the invention/Breadth of the claims. The claims are drawn to a method of testing for an agents ability to reduce HBV cccDNA in a non-human mammal or mammalian cells by introducing test agents in the mammal or cell that also comprises one or more polynucleotides that encode an HBV genome, wherein the genome comprises a segment encoding a mutated HBV core protein. The method does not require the presence of HBV. The core protein has mutations at positions 28, 30, 82, 84, 98, 100, 141, 143, 145, 146, 147, 148 or 149. Specific examples of amino acid mutations are R28A, L30A, R82A, L84A, R98A, L100A, S141A, S141D, S141R, S141T, L143A, L143I, E145D, T146A, T147A, V148I, and V149I; and R28A/R82A, R28A/R98A, R82A/R98A, R28A/R82A/R98A, R28A/L30A, R82A/L84A, R98A/L100A, T146A/T147A, and S141T/V148I/V149I.
State of the prior art/Predictability of the art. The state of the prior art teaches that in order to determine if an agent has anti-HBV properties (i.e., inhibits viral infection or replication), the virus would need to be present during a test of such an anti-HBV agent. Hu et al. (Antiviral Research, 2013, Vol. 99, pages 221-229) teaches that HBV inhibition can be detected by a decrease in cccDNA in the nucleus. Hu et al. reports that nucleos(t)ide therapy reduces cccDNA in the liver. [see page 221, right column] Hu et al. also teach that if cccDNA replenishment is reduced enough with anti-viral therapy, patients afflicted with HBV might be cured of the virus. [see page 222, left column]
Working examples. No working example is disclosed in the specification in which an agent is tested for its ability to reduce cccDNA of HBV inside a non-human mammal or mammalian cells. Applicants did discover that HBV with a core protein possessing the amino acid mutations S141A, L143I and T146A/T147A resulted in increased cccDNA in the cell exposed to the virus. [see working example 1] However, this working example did not just involve using a genome of HBV, but an intact hepatitis B virus.
Guidance in the specification. The specification provides guidance towards testing agents for cccDNA inhibition with HBV mutated core proteins present in a cell as claimed.
Amount of experimentation necessary. Additional research is required in order to determine how effective a method for screening for anti-HBV agents would be at reducing cccDNA in a non-human mammal or mammalian cell when the HBV core proteins are present, but not a hepatitis B virus. Furthermore, while applicants have revealed that 3 specific mutations to the core protein resulted in increased cccDNA in a cell, no test agents were looked according to the claimed method. Therefore, additional research is required to determine if these mutations would be susceptible to such a test agent.
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’s arguments have been considered, but they are not persuasive.
While applicants have amended the claimed method to require “cell that also comprises one or more polynucleotides that encode an HBV genome, wherein the genome comprises a segment encoding a mutated HBV core protein”, this limitation does not overcome the rejection. The method is intended to identify a test agent for use in reducing HBV in an individual by determining if the test agent reduces cccDNA of HBV. Applicants have not provided an example of what the test agent could be since they did not test any candidates. Identifying at least one specific agent capable of reducing HBV in an individual by only testing its ability to target the HBV genome would be not be sufficient since the virus possesses proteins/enzymes that are critical for viral infection and replication that would not be impacted by such a test agent. Also, the working example that applicants did provide in their specification showed that specific mutated Hepatitis B viruses exhibited increased cccDNA compared to a wildtype virus. Therefore, based on applicants working example, at least two hepatitis B viruses would be required to determine how much cccDNA was present in the mammalian cell. That being a mutated HBV and a wildtype HBV. Presently, the claim does not state a specific test agent or that the such viruses are used. With regard to applicant’s comments about US Patent 9657013 and the U.S. Patent application that this patent was issued from, each application is examined on its own merits.
Therefore, this rejection is maintained for reasons of record.
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.
(Prior Rejection Maintained) Claims 1-7 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.
Presently, claim 1, which are independent claims, are drawn to methods of testing agents for the inhibition of covalently closed circular DNA (cccDNA) of HBV inside cells, including inside of a non-human mammalian subject. In order for the detection of cccDNA of HBV inside a cell (in vitro or in vivo) to be monitored and compared to a control (thereby confirming inhibition), hepatitis B virus would also need to be present during the test. While applicants have amended the claims to recite: “cell that also comprises one or more polynucleotides that encode an HBV genome, wherein the genome comprises a segment encoding a mutated HBV core protein.” The claimed invention does not mention that a hepatitis B virus would be present during the method. Therefore, it is unclear how the method can achieve the identification of a test agent capable of reducing HBV in a cell or an individual without the involvement of hepatitis B virus, which would be providing the DNA that forms cccDNA. Therefore, these claims are viewed as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01.
Conclusion
No claims are 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 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