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 .
Applicant’s response filed 09/24/2025 has been received and considered entered. This is a response to amendments and arguments filed 09/24/2025.
Election/Restrictions
Claim 20 was withdrawn from further consideration 07/01/2025 pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/20/2024.
Claims Status
Claims 9, 18-19, 21-30, 36, and 50 is/are cancelled. Claims 59-60 are new. Claims 1-8, 10-17, 20, 31-35, 37-49, and 51-60 is/are currently pending with claim 20 withdrawn. Claims 1-8, 10-17, 31-35, 37-49, and 51-60 is/are under examination.
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
112(a):
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.
Claim 51-53 is 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 the claimed method in vitro and ex vivo, does not reasonably provide enablement for in vivo methods. 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.
This rejection is maintained.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
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, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims:
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed method is that it encompasses a method of successfully editing a target nucleic acid in vivo. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The amount of direction provided by the inventor and the level of predictability in the art:
The specification teaches methods of transforming cells in vitro and ex vivo (pages 83-84), in addition to methods of delivering compositions to cells (pages 86-87); however, the specification does not disclose methods that would facilitate specifically in vivo methods of introducing compositions into cells. The art at the time of filing taught that Cas12i has the potential for use in in vivo methods, but had not at the time been used successfully in vivo (see Yan, 2019, page 490). The specification as filed does not provide guidance that overcomes this unpredictability within the art.
The existence of working examples:
What is enabled by the working examples is narrow in comparison to the breadth of the claims: The specification discloses in vitro methods of using a Cas12i fusion protein for editing of a nucleic acid, but does not disclose in vivo methods of nucleic acid editing (Figs. 1-10).
The quantity of experimentation needed to make or use the invention:
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given that the nature of the invention encompasses in vitro, ex vivo, and in vivo methods of nucleic acid editing, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials or in animals in vivo, in order to demonstrate the invention could be used in vivo with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully treating any CNS disorder or neurodegenerative disease. Therefore, Claims 51-53 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
Claims 1-8, 10-17, 31-35, 37-49, and 51-60 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 rejection is maintained and modified in response to the amendments and arguments filed 09/24/2025.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
Claim 1 broadly recites that the fusion protein comprises a deaminase domain. Claims 33-35, dependent on claim 1, recite “a variant” of SEQ ID NOs:28-29, creating an enormous genus of sequences.
The specification does not define the term “variant”, and merely provides a number of species of variant deaminase domains and possible embodiments (page 43 line 2-page 45 line 10). This does not adequately define the genus created by the claim limitations.
As discussed above, the claims and specification do not recite representative numbers of species, nor do they recite or disclose sufficient structural, sequence, or functional elements that further define or limit the genera created by the claim limitations, beyond the structural and functional elements which define all species (e.g., that deaminase proteins are capable of deaminating nucleic acids), as discussed above.
According to the MPEP § 2163, "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 (see i)(A) above), reduction to drawings (see i)(B) above), 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 i)(C) above). 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. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
The claims create enormous genus of deaminase polypeptide sequences, but neither the claims nor the specification recite or disclose sufficient definitions or limitations to this genus, nor do they provide representative numbers of species for the genus. Claims 2-8, 10-17, 31-32, 37-49, and 51-60 read on the breadth of claim 1, encompassing the “variant” deaminase sequences of claims 33-35. As such, claims 1-8, 10-17, 31-35, 37-49, and 51-60 lack adequate written description for the full breadth of the claimed invention. Removal of the limitation “or a variant thereof” from claims 33-35 would obviate this rejection.
Response to Arguments
Applicant's arguments filed 09/24/2025 have been fully considered but they are not persuasive.
Applicant argued on page 13 of arguments that “clinical trial data is not required to meet the enablement standard for chemical or biological applications”; that claim 51 is adequately enabled because the “instant specification clearly demonstrates that Cas12i fusion proteins falling within the scope of the claims are able to introduce a substitution in a target sequence of a target nucleic acid in a cell”; and that US 10808245 B2, incorporated by reference, “provides extensive description of delivery of CRISPR systems in vivo”. While clinical trial data is not required to meet the enablement requirement, the prior art at the time of filing did not teach that Cas12i proteins had been introduced to cells in vivo, and the disclosure does not provide evidence of in vivo or ex vivo methods (the specification only discloses in vitro methods of using a Cas12i fusion protein for editing of a nucleic acid, not in vivo methods of nucleic acid editing, Figs. 1-10); as such, neither the prior art nor the disclosure provide sufficient evidence enabling the full scope of the methods of claims 51-53. As claim 51 encompasses ex vivo and in vivo introduction of the claimed Cas12i fusion proteins, and claims 52-53 recite that the cell is in vivo or ex vivo, claim 51 is not limited to in vitro methods, while the disclosure is only enabling of in vitro methods. Patent ~245 teaches in vivo methods of introducing Cas12i proteins in bacteria; as such, ~245 does not provide an enabling disclosure for in vivo methods of introducing Cas12i in multicellular organisms, including multicellular eukaryotes such as rodents and humans. As such, Applicant’s arguments are not considered persuasive, and the rejection of pending claims 51-53 under 35 USC 112(a) for scope of enablement is maintained.
Applicant argued on page 14 of arguments that amendment of “claims 33-35 to no longer recite ‘functional fragment’” renders the written description rejection moot. However, the claim limitation rejected for lack of written description was “a functional fragment or variant”. However, this amendment only addresses the lack of written description of “functional fragments” of deaminase domains, not of “variants” of deaminase domains. The applicant does not further address deaminase domain variants in arguments. As described in the rejection above, the disclosure does not provide a sufficient description or representative number of species of the claimed genus of deaminase domain “variants”. As such, the rejection of pending claims 1-8, 10-17, 31-35, 37-49, and 51-60 for lack of sufficient written description is maintained.
Conclusion
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.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635