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 .
Application Status
Applicant’s remarks and amendments to the claims filed February 18, 2026 are acknowledged. Claims 1, 15, 38, 85, 87, 89, and 98 were amended. Claims 1-3, 5, 7, 11, 13, 15-18, 20, 25, 27-29, 33, 38, 43-44, 48-50, 55, 62-63, 85-103 are pending.
Withdrawn Rejections
Applicant’s amendments to the claims resolve the claim objections raised in the prior action. These objections are withdrawn. The amendments to claim 15 also resolve the § 112(d) rejections raised in the prior action. This rejection is withdrawn, accordingly.
Claim 1 recites “said adenosine deaminase protein or catalytic domain thereof comprises a modification to reduce off-target effects relative to a wild-type adenosine deaminase, wherein the modification comprises mutations at positions V351, S486, T375, S370, P462, N597, and S495 relative to human adenosine deaminase that act on RNA 2 (hADAR2)….” MPEP 2111.03(I) states that the phrase “comprising” “means that the named elements are essential, but other elements may be added….” Accordingly, the adenosine deaminase protein or catalytic domain thereof is understood to require, at least, mutations at each of the recited positions relative to hADAR2. This amendment is sufficient to overcome the § 103 rejections raised in the prior action over primary references Liu and Koonin, and the non-statutory double patenting rejection over Patent No. 11,180,751 (i.e., Koonin). These rejections are withdrawn, accordingly. The non-statutory double patenting rejections over co-pending Application No. 16/772,269 have also been considered with respect to the subject matter of the instant claims. This rejection is withdrawn, at least because the instant claims and co-pending claims are directed to distinct nucleic acid targets (i.e., DNA vs. RNA).
Applicant’s remarks and amendments to the claims have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Restriction/Election
Applicant has requested a “specific explanation as to how claim 102 is alleged to be beyond the scope of the election set forth in the response to the Restriction Requirement.” Applicant argues that claim 102 “further limits the adenosine deaminase recited in the elected method.” Applicant elected an “adenosine deaminase” in the response filed September 11, 2024. Claim 102 depends from claim 49, which recites that “the [modified] nucleotide comprises Cytosine.” Claims 49-50 were withdrawn in each of the prior actions as being drawn to a non-elected species: a cytidine deaminase protein, i.e., a deaminase which deaminates cytosine. Claims 49 and 102, therefore, are not directed to the elected species, because they require a cytidine deaminase protein, i.e., a deaminase which deaminates cytosine, not an adenosine deaminase, i.e., a deaminase which deaminates adenosine.
Accordingly, claims 28, 49-50, 55, 62-63, 95-99, and 102-103 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species. Claims 1-3, 5, 7, 11, 13, 15-18, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101 are under examination below.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/610,041 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 62/610,041 does not disclose an adenosine deaminase or catalytic domain thereof with an “S370” mutation relative to hADAR2. The first disclosure of an “S370” mutation is in PCT/US2018/067207 ([0351]). Accordingly, all claims under examination have an effective filing date of December 21, 2018.
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 92 and 101 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. The rejections that follow are maintained from the prior action.
Claim 92 recites “wherein when the one or more polynucleotide molecules are comprised within one or more vectors.” It is not clear what is required when the one or more polynucleotides are comprised within one or more vectors because this phrase is incomplete, and therefore, the scope of the claim is unclear.
Claim 101 recites an adenosine deaminase protein which is “a mutated hADAR1d” comprising “corresponding mutations” to mutations “T375G/S, N473D, or both” in hADAR2d. It is not clear based on the claim or specification what defines a “corresponding mutation” in hADAR1d, to the recited mutations in hADAR2d. The specification generally describes the recited positions in adenosine deaminase, and generally describes various adenosine deaminases (see at least [0301]-[0363]). The specification provides corresponding mutations in hADAR1d to two hADAR2d mutations, i.e., G487 and E488 ([0308]). However, these unrelated examples and general guidance do not define the “corresponding mutations” in hADAR1d to mutations “T375G/S, N473D, or both” in hADAR2d.
Even should the positions of the “corresponding mutations” be clear and determinable, it is not clear what would constitute a “mutation” at the corresponding position. For example, consider that the amino acid at the corresponding position in hADAR1d to “T375” of hADAR2d was not threonine, but serine. It is not clear whether the serine would need to be changed to a different amino acid to be considered a “mutation,” or whether, because serine is not threonine, it is already considered a “mutation.” Furthermore, it is not clear in the former case, whether changing the serine to a threonine would be considered a “mutation,” because, while this would be a mutation relative to the corresponding position in hADAR1d, it is the recited amino acid at position 375 of hADAR2.
Response to Remarks – 35 USC § 112(b)
Applicant submits that the amendments to the claims overcome the § 112(b) rejections raised in the prior action. However, no amendments were made to claims 92 or 101, over which the rejections above are maintained, accordingly.
Notice to Joint Inventors
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim Rejections - 35 USC § 103 – Zhang in view of Jones
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5, 7, 11, 13, 15-18, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101 are rejected under 35 U.S.C. 103 as being obvious over Zhang (Zhang et al., US 2021/0009972 A1, effectively filed 4 October 2018 for the subject matter relied upon herein) in view of Jones (Jones et al., US 2021/0163944 A1, effectively filed 26 October 2018 for the subject matter relied upon herein). The rejections that follow are new and necessitated by Applicant’s amendments to require an adenosine deaminase or catalytic domain thereof comprising mutations at each of the recited positions in claim 1.
The applied references, Zhang and Jones, have a common applicant and common inventors with the instant application. Based upon the earlier effectively filed date of the references, they constitute prior art under 35 U.S.C. 102(a)(2). The following rejections under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the references was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Zhang teaches a method of modifying an adenine in a target locus, comprising delivering to said locus: (a) a catalytically inactive (dead) Cas or Cas nickase protein; (b) a guide molecule which comprises a guide sequence linked to a direct repeat sequence; and (c) an adenosine deaminase protein or catalytic domain thereof; wherein said adenosine deaminase protein or catalytic domain thereof is covalently or non- covalently linked to said dead Cas or Cas nickase protein or said guide molecule, or is adapted to link thereto after delivery, wherein said guide molecule forms a complex with said dead Cas or Cas nickase protein and directs said complex to bind a first DNA strand at said target locus, resulting in a mismatch in a heteroduplex formed by the guide sequence and the target locus ([0034]; [0145]). Zhang teaches the adenosine deaminase protein or catalytic domain thereof comprises a modification to reduce off-target effects relative to a wild-type adenosine deaminase, wherein the modification comprises mutations at positions V351, S486, T375, S370, P462, N597, and S495 relative to human adenosine deaminase that act on RNA 2 (hADAR2)([0040]; [0171]-[0248]).
Zhang suggests that their invention can be “extended” to use of other Cas proteins, including C2c1 ([0337]; [0393]), but does not teach a catalytically inactive C2c1 or C2c1 nickase protein.
However, Jones teaches a catalytically inactive C2c1 or C2c1 nickase protein covalently or non-covalently linked to an adenosine deaminase protein or catalytic domain thereof comprising one or more mutations, for the same purposes as described by Zhang (“an engineered system for site directed base editing comprising a targeting domain and an adenosine deaminase… or catalytic domain thereof, wherein the targeting domain comprises a Cas12b effector protein, or a fragment thereof… the Cas12b effector protein is catalytically inactive… the Cas12b effector protein is selected from Table 1 or Table 2… the Cas12b effector protein originates from… Alicyclobacillus kakegawensis,” [0024]-[0025]; [0545]-[0558]; [0591]-[0706]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the catalytically inactive (dead) Cas or Cas nickase protein of Zhang, for a catalytically inactive (dead) C2c1 or C2c1 nickase protein taught by Jones. It would have amounted to a simple substitution of two known Cas proteins covalently or non-covalently linked to adenosine deaminase or catalytic domain thereof, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in substituting the Cas proteins because Zhang and Jones are directed to substantially identical subject matter (i.e., Cas protein-adenosine deaminase fusions), and as evidenced by Zhang and Jones, linking a Cas protein to an adenosine deaminase comprising one or more mutations was well within the purview of the skilled artisan. Zhang teaches that their invention may be “extended based on aspects of CRISPR-Cas development and use” as described in the prior art, “particularly as it relates to delivery of a CRISPR protein complex and uses of an RNA guided endonuclease in cells and organisms ([0337]). Zhang cites prior art which describes C2c1 proteins with differing properties from the Cas proteins taught by Zhang ([0393]). The skilled artisan would have been motivated to substitute the Cas proteins in an effort to “extend” Zhang’s invention using Cas proteins with differing properties, which could be beneficial in different investigative and therapeutic applications.
Regarding claim 2, Zhang teaches the adenosine deaminase or catalytic domain thereof is fused to the N- or C-terminus of the Cas protein ([0012]).
Regarding claims 3 and 87, Zhang teaches the adenosine deaminase or catalytic domain thereof is fused to the Cas protein by a linker, wherein the linker comprises “(GGGGS)3” ([0012]).
Regarding claims 5 and 88, Zhang teaches the adenosine deaminase or catalytic domain thereof may be linked to an adaptor protein, and the guide molecule or the Cas protein comprises an aptamer sequence capable of binding to the adaptor protein ([0013]). Zhang teaches the adaptor protein may be BZ13 ([0013]).
Regarding claim 7, Zhang teaches that the adenosine deaminase protein or catalytic domain thereof is inserted in an internal loop of the Cas protein ([0014]).
Regarding claim 11, Zhang teaches the guide molecule binds to the Cas protein and is capable of forming a heteroduplex of about 20nts with the target sequence, or of more than 20nts with the target sequence (Figs. 1-2; [0256]-[0257]).
Regarding claims 13 and 16, Zhang teaches the adenosine deaminase or catalytic domain thereof comprises an E488Q mutation ([0009]), which as evidenced by Zhang, fulfills the functional limitations of the claims ([0986]).
Regarding claim 15, Zhang teaches the Cas protein comprises one or more heterologous NLSs ([0020]).
Regarding claim 17, Jones teaches a C2c1 protein comprising a polypeptide with the sequence SEQ ID NO: 518 (Table 14), which is at least 80% identical to instant SEQ ID NO: 64 (i.e., 99.8% identical). See attached alignment in Appendix I.
Regarding claim 18, Jones teaches an AacC2c1 protein, which recognizes the PAM sequence of “TTN,” wherein “N is A/C/G or T” ([0167]).
Regarding claims 20 and 90, Zhang teaches the target locus is within a cell, wherein the cell is a eukaryotic cell ([0159]).
Regarding claim 25, Zhang teaches the target locus is within an animal or within a plant ([0159]).
Regarding claim 27, Zhang teaches the target locus is comprised in a DNA molecule in vitro ([0161]).
Regarding claims 29 and 33, Zhang teaches that the components (a), (b), and (c) are delivered to a cell as one or more polynucleotide molecules ([0024]; [0800]).
Regarding claim 38 and 85, Zhang teaches the method reverts a G[Wingdings font/0xE0] A point mutation caused by a disease or a pathogenic SNP ([0026]), wherein the disease is “cancer” ([0160]).
Regarding claim 43, the nucleotide in the method rendered obvious above comprises adenine ([0034]).
Regarding claim 44, the guide sequence in the method rendered obvious above comprises a non-pairing cytosine at a position corresponding to an adenine, so that an A-C mismatch is present in the heteroduplex formed between the guide sequence and target sequence ([0034]).
Regarding claim 48, Zhang teaches a human adenosine deaminase or catalytic domain thereof ([0173]).
Regarding claim 86, Regarding claim 86, MPEP 2112.01 states that "when the structure recited in the reference is substantially identical to that of the claims, claim properties or functions are presumed to be inherent." In the instant case, the claim recites that the "C2c1 nickase protein nicks a second DNA strand at said target locus displaced by formation of said heteroduplex." The structure rendered obvious for use in the method above, and the claimed structure are substantially identical, i.e., they are both C2c1 nickase proteins, having a mutation in one of the residues recited in the specification at [0152]). See paragraphs [0545]-[0558] of Jones. Thus, the function of the C2c1 nickase protein recited in claim 86 is inferred as inherent to the obvious process comprising a substantially identical structure.
Regarding claim 89, Zhang teaches the adenosine deaminase or catalytic domain thereof may comprise one or more heterologous NLSs ([0020]).
Regarding claim 91, Zhang teaches polynucleotide molecules which are mRNA molecules encoding components (a) and/or (c) ([0024]).
Regarding claims 92-94, Zhang teaches one or more vectors comprising the one or more polynucleotide molecules, wherein the one or more polynucleotide molecules comprise one or more regulatory elements, wherein the regulatory elements comprise inducible promoters ([0024]).
Regarding claim 100, Zhang teaches the adenosine deaminase or catalytic domain thereof is a hADAR2 comprising an E488Q mutation ([0017]-[0018]).
Regarding claim 101, Zhang teaches that the adenosine deaminase protein or catalytic domain thereof is a mutated hADAR2d comprising the mutation T375G/S, N473D, or both, or a mutated hADAR1d comprising corresponding mutations ([0193]; [0207]; [0216]).
Response to Remarks - 35 USC § 103
Applicant’s remarks regarding the § 103 rejections raised in the prior action have been reviewed. Applicant’s remarks are moot, because the new grounds of rejection herein do not rely on any reference applied in the prior rejections of record for any teaching or matter specifically challenged in the remarks.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Application No. 17/265,910
Claims 1, and 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 59 of co-pending Application No. 17/265,910. Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. The rejection that follows is new and necessitated by Applicant’s amendments to the claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending claim 59 recites “A method of modifying an adenine or cytosine in a target oligonucleotide, comprising delivering to said target oligonucleotide: (a) the engineered composition of claim 49; (b) a guide molecule which comprises a guide sequence linked to a direct repeat; and (c) an adenosine deaminase protein or catalytic domain thereof or a cytidine deaminase protein or catalytic domain thereof; wherein said adenosine deaminase protein or catalytic domain thereof or the cytidine deaminase protein or catalytic domain thereof is covalently or non-covalently linked to said Cas12b effector protein or said guide molecule is adapted to or linked thereto after delivery; wherein said guide molecule forms a complex with said Cas 12b effector protein and directs said complex to bind said target oligonucleotide, wherein said guide sequence is capable of hybridizing with a target sequence within said target oligonucleotide to form an oligonucleotide duplex, optionally wherein: (A) said Cytosine is outside said target sequence that forms said oligonucleotide duplex, wherein said cytidine deaminase protein or catalytic domain thereof deaminates said Cytosine outside said oligonucleotide duplex, or (B) said Cytosine is within said target sequence that forms said oligonucleotide duplex, wherein said guide sequence comprises a non-pairing Adenine or Uracil at a position corresponding to said Cytosine resulting in a C-A or C-U mismatch in said oligonucleotide duplex, and wherein the cytidine deaminase protein or catalytic domain thereof deaminates the Cytosine in the oligonucleotide duplex opposite to the non-pairing Adenine or Uracil, optionally wherein said adenosine deaminase protein or catalytic domain thereof deaminates said Adenine or Cytosine in the oligonucleotide duplex.”
The engineered composition of claim 49 is “An engineered composition for site directed base editing comprising: (a) a targeting domain and (b) an adenosine deaminase, cytidine deaminase, or catalytic domain thereof, and (c) a guide molecule, wherein the targeting domain comprises a Cas12b effector protein or a polynucleotide encoding the Cas12b effector protein, wherein the Cas12b effector protein is at least 95% identical to SEQ ID NO: 519, wherein the Cas12b effector protein comprises one or more mutations at amino acid positions selected from K846, S893, E837, or any combination thereof relative to SEQ ID NO: 519, and wherein said adenosine or cytidine deaminase protein or catalytic domain thereof is covalently or non-covalently linked to said Cas12b effector protein,” “wherein the Cas12b effector protein is catalytically inactive.”
It is noted that co-pending SEQ ID NO: 519 meets the limitations of instant claims 17-18.
Regarding instant claims 1, and 17-18, the co-pending claim does not recite that the nucleotide deaminase is an adenosine deaminase comprising one or more of the mutations recited in instant claim 1. However, the co-pending claims are also directed to a C2c1 protein linked to an adenosine deaminase, which comprises the mutations recited in instant claim 1. See co-pending claims 8 and 86.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used an adenosine deaminase or catalytic domain thereof in the co-pending method which is mutated at the positions recited in the co-pending claim, to arrive at instant claim 1, and 17-18. It would have amounted to modifying a known adenosine deaminase or catalytic domain thereof used in a known method, with known mutations, by known means to yield predictable results. The skilled artisan would have been motivated to use an adenosine deaminase or catalytic domain thereof with the mutations recited in the co-pending claims, to arrive at the instant claims, with a reasonable expectation of success, because the co-pending claims clearly establish that an adenosine deaminase or catalytic domain thereof mutated at the recited positions is compatible with a C2c1 protein, and therefore, could be used in the co-pending methods requiring a C2c1 protein linked to an adenosine deaminase protein.
Claims 2-3, 5, 7, 11, 13, 15-16, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 59 of co-pending Application No. 17/265,910 in view of Zhang (Zhang et al., US 2021/000972 A1, effectively filed 4 October 2018 for the subject matter relied upon herein). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. The rejection that follows is new and necessitated by Applicant’s amendments to the claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 2-3, 5, 7, 11, 13, 15-16, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101, the teachings of Zhang are described above and applied hereinafter.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the teachings of Zhang to the method rendered obvious above, to arrive at the methods of instant claims 2-3, 5, 7, 11, 13, 15-16, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101. It would have amounted to applying known methods of configuring and using C2c1 protein-adenosine deaminase fusion proteins and guide molecules, by known means, to yield predictable results. The skilled artisan would have been motivated to apply Zhang’s teachings to the obvious methods, with a reasonable expectation of success, because Zhang and the co-pending claims teach substantially identical methods of using catalytically inactive Cas proteins or Cas nickases linked to a mutated adenosine deaminase protein, and methods of preparing and using systems comprising such proteins were known in the art as evidenced by Zhang.
Application No. 16/773,000
Claims 1-3, 5, 7, 11, 13, 15-16, 18, 20, 25, 27, 29, 33, 38, 43-44, 48, 85-94, and 100-101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 232 of co-pending Application No. 16/773,000 in view of Zhang (Zhang et al., US 2021/000972 A1, effectively filed 4 October 2018 for the subject matter relied upon herein). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. The rejection that follows is new and necessitated by Applicant’s amendments to the claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending claim 232 recites “A method of treating alpha-1 antitrypsin deficiency (AATD), comprising: administering, to a subject in need thereof, an engineered composition for modifying a target locus comprising: (a) a Type V-B Cas protein, or a polynucleotide encoding the Type V-B Cas protein, wherein the Type V-B Cas protein is catalytically inactive (dCas); and (b) a guide molecule, or a polynucleotide encoding the guide molecule, wherein the guide molecule comprises a scaffold and a guide sequence and is capable of forming a complex with the Type V-B dCas protein and directing sequence-specific binding of the complex to a target sequence in a target polynucleotide, wherein the target sequence is a SERPINA1 gene; and (c) one or more heterologous functional domains covalently linked to the Type V-B dCas protein, wherein at least one heterologous functional domain is an adenosine deaminase or cytidine deaminase,” and wherein the Type V-B Cas protein is a C2c1 protein originating from “Bacillus hisashii strain C4.”
It is noted that the limitation “Bacillus hisashii strain C4” meets the limitations of instant claim 18.
The co-pending claim does not recite the mutations required of the adenosine deaminase, or the limitations regarding the mismatch in the heteroduplex. The teachings of Zhang are described above and applied hereinafter. The obviousness of modifying the co-pending method with the teachings of Zhang, to arrive at the methods of instant claims 1 and 18 is described in paragraph 43 above, and applied hereinafter.
Co-pending claims 234-242 teach the limitations of co-pending claims 29, 33, and 92-93. These claims are also obvious over Zhang.
Regarding claims 2-3, 5, 7, 11, 13, 15-16, 20, 25, 27, 38, 43-44, 48, 85-91, 94, and 100-101, the teachings of Zhang are described above and applied hereinafter. The obviousness of modifying the obvious method with the teachings of Zhang, to arrive at the methods of instant claims 2-3, 5, 7, 11, 13, 15-16, 20, 25, 27, 38, 43-44, 48, 85-91, 94, and 100-101 is described in paragraph 43 above, and applied hereinafter.
Claim 17 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 232 of co-pending Application No. 16/773,000 in view of Zhang (Zhang et al., US 2021/000972 A1, effectively filed 4 October 2018 for the subject matter relied upon herein) and Jones (Jones et al., US 2021/0163944 A1, effectively filed 26 October 2018 for the subject matter relied upon herein). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. The rejection that follows is new and necessitated by Applicant’s amendments to the claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 17, the co-pending claims do not set forth SEQ ID NOs for the encompassed C2c1 proteins. The teachings of Jones are described above and applied hereinafter. The obviousness of substituting the generic C2c1 proteins of the co-pending claims, with a specific sequence taught by Jones corresponding to the C2c1 proteins, is described in paragraph 14 above and applied herein with respect to instant claim 17.
Response to Remarks – Nonstatutory Double Patenting
Applicant’s remarks regarding the nonstatutory double patenting rejections raised in the prior action have been reviewed. Regarding the co-pending applications, the nonstatutory double patenting rejections are not the only remaining rejections, and as described above, overlap remains between the co-pending and instant claims. No terminal disclaimers have been filed. The rejections remain outstanding.
Conclusion
No claims are allowed.
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 JENNA L PERSONS whose telephone number is (703)756-1334. The examiner can normally be reached M-F: 9-5pm.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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