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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Election filed May 8, 2026.
Claims 8-19 have been canceled. Claim 1 has been amended.
Claims 1-7, 24, 39, 78, 97, 106, 108, 116, 123 and 124 are pending in the instant application.
Election/Restrictions
Applicant’s election of Group IV in the reply filed on May 8, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 39, 78, 97, 106, 108, 116, 123 and 124 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1-7 and 24 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statements (IDS) filed May 8, 2026 (14), (18), (16), (18), (10), (14), and (5) pages are acknowledged. The submissions are in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statements, and signed copies are enclosed herewith.
Applicant’s IDS filed June 25, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 8, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s information disclosure statements (IDS) filed February 29, 2024 (13) and (7) pages are acknowledged. The submissions are in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statements, and signed copies are enclosed herewith.
Applicant’s IDS filed September 13, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed May 3, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s information disclosure statements (IDS) filed June 13, 2022 (6), (17), and (8) pages are acknowledged. The submissions are in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statements, and signed copies are enclosed herewith.
Applicant’s IDS filed November 9, 2021 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed November 9, 2021 are acknowledged and have been accepted by the Examiner.
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.
Claim 4 is 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 pre-AIA the applicant regards as the invention.
Claim 4 is rejected because the claim recites the phrase, “wherein the cell is in vivo or ex vivo”. The claim is rejected for a lack of antecedent basis because claim 1 from which claim 4 depends never makes reference to a cell. Appropriate correction is required.
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 1-7 and 24 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. This is a written description rejection.
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 requirement 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 Eli 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 disclosure must provide written 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 and that applicant was in possession of the claimed genus.
The instant claims are drawn to a method of editing a nucleobase of a hepatitis B virus (HBV) genome, the method comprising contacting the HBV genome with one or more guide RNAs and a base editor comprising a polynucleotide programmable DNA binding domain and an adenosine deaminase or cytidine deaminase domain, wherein said guide RNA targets said base editor to effect an alteration of the nucleobase of the HBV genome, and wherein the alteration of the nucleobase results in an R87* or W120* termination in an HBV X protein. As discussed below, there is insufficient written description for the guide RNA encompassed by the claims.
The instant Specification provides examples of in silico analysis of the amino acid substitutions resulting from base editing with a particular guide RNA selected for targeting conserved regions of the HBV genome. See Table 20. More specifically, Table 20 discloses guide sequence, SEQ ID NO:354 produced a premature termination codon introducing a R87STOP and SEQ ID NO:493 produced a premature termination codon introducing a W120STOP in the HBV genome.
The art teaches gRNAs exhibiting high target site conservation across HBV isolate sequences in the HBVdb database23 that, in combination with the cytosine base editor, were predicted to introduce missense mutations in HBV genes. See Smekalova et al. (Molecular Therapy: Nucleic Acids Vol. 35 March 2024, pages 1-13, plus Supplementary Information). See Table 20. NOTE: Smekalova et al. teach the sequence represented by SEQ ID NO:354 of the present invention as a gRNA which introduces a Stop-codon in the HBV X gene. See Smekalova et al. EMSbeam95.
There is insufficient written description for the guide RNAs encompassed by the claims because the application does not adequately describe or represent the entire genus of guide RNAs which carry out the functionality of the present invention. Namely, guide RNA in combination with a base editor to effect an alteration of the nucleobase of the HBV genome, wherein the alteration of the nucleobase results in an R87* or W120* termination in an HBV X protein. Only SEQ ID NO:354, resulting in R87STOP and SEQ ID NO:493, resulting in W120STOP have been described and reduced to practice.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350. However, written description requirement for claims that required a guide RNA in combination with a base editor to effect an alteration of the nucleobase of the HBV genome, and wherein the alteration of the nucleobase results in an R87* or W120* termination in an HBV X protein is not met.
The entire genus of guide RNAs that function as claimed does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of guide RNAs nor any structure/function correlation that would enable one of skill to immediately envision the genus of guide RNAs in combination with a base editor that alter the nucleobase resulting in an R87* or W120* in an HBV X protein required to practice the full scope of the invention. Only the single species, SEQ ID NO:354 for R87STOP and the single species SEQ ID NO:493 for W120STOP have been exemplified.
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of guide RNAs embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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