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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08 April 2026 has been entered.
Status of Application
The response filed on 08 April 2026 is acknowledged and has been considered in its entire. Claims 26 and 33-37 remain pending and subject to examination.
Information Disclosure Statement
The information disclosure statements (IDS) submitted 08 April 2026 has been considered, see initialed and signed PTO/SB08.
Terminal Disclaimer
The terminal disclaimer filed on 24 September 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 10760064 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Maintained Rejection(s)
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.
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 22-27 of U.S. Patent No. 9512446. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘446 patent anticipate and/or render obvious the instant claims.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘446 patent in their broadest are drawn to an isolated Streptococcus pyogenes Cas9 (SpCas9) protein with mutations at one or both of Q695 and Q926 in SEQ ID NO: 1, and optionally wherein the SpCas9 protein is fused to one or more of a nuclear localization sequence, cell penetrating peptide sequence, and/or affinity tag (claim 1); with dependent claims 6-7 reciting the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent claim 8-10 recites the fusion protein further comprises an activation domain, selected from VP64 or NF-kB p65. Dependent claims 22-24 recites the fusion protein is encoded by nucleic acid within a vector and expressed in a host cell. While the ‘446 patent claims do not recite what type of host cell comprises the fusion protein(s), consistent with MPEP 804(II)(B)(1), upon construing the scope of the claims and specifically the scope of “host cell” consistent with specification of the ‘446 patent, it is clear that the host cells encompass mammalian and human host cells (See Examples utilizing human cells and See Col. 5, lines 48-53).
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 23-30 of U.S. Patent No. 10093910. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘910 patent anticipate and/or render obvious the instant claims.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘910 patent in their broadest are drawn to an isolated Streptococcus pyogenes Cas9 (SpCas9) protein that has at least 95% sequence identity to SEQ ID NO: 1, with mutations at one or both of Q695 and Q926, and wherein the protein retains the ability to interact with a guide RNA and target DNA (claim 1), with dependent claim 2 reciting the protein is further fused to a NLS sequence, etc.; dependent claims 7-8 recites the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent claim 9-11 recites SpCas9 is in a fusion protein that further comprises an activation domain, selected from VP64 or NF-kB p65. Dependent claims 23-25 recites the fusion protein is encoded by nucleic acid within a vector and expressed in a host cell. While the ‘910 patent claims do not recite what type of host cell comprises the fusion protein(s), consistent with MPEP 804(II)(B)(1), upon construing the scope of the claims and specifically the scope of “host cell” consistent with specification of the ‘910 patent, it is clear that the host cells encompass mammalian and human host cells (See Examples utilizing human cells and See Col. 5, lines 45-51).
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 23-27 of U.S. Patent No. 10633642. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘642 patent anticipate and/or render obvious the instant claims.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘642 patent in their broadest are drawn to a Streptococcus pyogenes Cas9 (SpCas9):single guide RNA (sgRNA) complex comprising a SpCas9 protein with mutations at one or both of Q695 and Q926 in SEQ ID NO: 1, and a sgRNA (claim 1), with dependent claim 2 reciting the protein is further fused to a NLS sequence, etc.; dependent claims 7-8 recites the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent claim 9-11 recites SpCas9 is in a fusion protein that further comprises an activation domain, selected from VP64 or NF-kB p65. Dependent claims 23-24 recites the fusion protein is encoded within a vector and expressed in a host cell. While the ‘642 patent claims do not recite what type of host cell comprises the fusion protein(s), consistent with MPEP 804(II)(B)(1), upon construing the scope of the claims and specifically the scope of “host cell” consistent with specification of the ‘642 patent, it is clear that the host cells encompass mammalian and human host cells (See Examples utilizing human cells and See Col. 5, lines 53-60).
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 27-33 of U.S. Patent No. 9926545. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘545 patent anticipate and/or render obvious the instant claims.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘545 patent in their broadest are drawn to an isolated variant Streptococcus pyogenes Cas9 (SpCas9) protein, comprising an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 1, with a mutation at D1135 and optionally at one or more of the following positions: G1104, S1109, L1111, S1136, G1218, N1317, R1335, T1337, wherein the isolated variant SpCas9 protein can interact with a guide RNA and a target DNA (claim 1), with dependent claims 4-5 reciting the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent claim 13-15 recites SpCas9 is in a fusion protein that further comprises an activation domain, selected from VP64 or NF-kB p65. Dependent claim 27 recites the fusion protein is expressed in a host cell. While the ‘545 patent claims do not recite what type of host cell comprises the fusion protein(s), consistent with MPEP 804(II)(B)(1), upon construing the scope of the claims and specifically the scope of “host cell” consistent with specification of the ‘545 patent, it is clear that the host cells encompass mammalian and human host cells (See Examples utilizing human cells and See Col. 4, lines 16-25).
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 24-35 of U.S. Patent No. 10479982. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘982 patent anticipate and/or render obvious the instant claims.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘982 patent are drawn to an isolated variant Streptococcus pyogenes (SpCas9) protein comprising an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 1, with an amino acid mutation at G1218 and optionally at one or more of the following positions: G1104, S1109, L1111, E1219, D1135, N1317, R1335, T1337, wherein the isolated variant SpCas9 protein can interact with a guide RNA and a target DNA (claim 1). Dependent claims 5-6 recite the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent claim 10-12 recites SpCas9 is in a fusion protein that further comprises an activation domain, selected from VP64 or NF-kB p65. Dependent claims 24-29 recites the variant protein is expressed in a host cell. While the ‘982 patent claims do not recite what type of host cell comprises the fusion protein(s), consistent with MPEP 804(II)(B)(1), upon construing the scope of the claims and specifically the scope of “host cell” consistent with specification of the ‘982 patent, it is clear that the host cells encompass mammalian and human host cells (See Examples utilizing human cells and See Col. 4, lines 1-57; Examples).
Claims 26 and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 23-35 of U.S. Patent No. 11286468.
The instant claims in their broadest are drawn to a mammalian cell expressing a fusion protein comprising a catalytically inactive S. pyogenes Cas9 protein linked to a heterologous functional domain, wherein the catalytically inactive Cas9 protein comprises mutations at D10 and H840, and wherein the heterologous functional domain is VP64, the order of the fusion protein (claim 33), said fusion comprises linkers and/or nuclear localization sequence or epitope tag (claim 34), the kind of epitope tag selected from c-myc, Hisx6 and FLAG (claim 35) and the fusion protein is expressed from a vector in said cell (claim 36).
The claims to the ‘468 patent are drawn An Streptococcus pyogenes Cas9 (SpCas9) protein, comprising an amino acid sequence that has at least 80% sequence identity to the amino acid sequence of SEO ID NO: 1, with mutations at all six of the following positions: D1135, S1136, G1218, E1219, R1335, and T1337, wherein the mutations are LRSVQL, LRKIQK, LRSVQK, LWKIQK, VRKIQK, IRAVQL, GRKIQK, SWRVW, SWKVLK, TAHFKV, MWVHLN, KRRCKV, VRAVQL, SRMHCK, GWKLLR, GWKOQK, VAKLLR, VAKIQK, VAKILR, GRKILR, VRKLLR, IRAVQL, MQKSER, VRKSER, ICKSER, LRSVER, MQSVQL, ICCCER, LWRWA, WMQAYG, LWRSEY, MCSFER, LWMREQ, FMQWVN, YCSWVG, MCAWCG, FMQWVR, MRARKE, LRLSAR, KWMMCG, AWNFQV, LWTTLN, CWCQCV, AEEQQR, GWEKVR, NRAVNG, LRSYLH, VQDAQR, GWRQSK, AWLCLS, KWARW, VKMAKG, QRKTRE, LCRQQR, CWSHQR, SRTHTQ, or LWEVIR. Dependent claims 2-3 recite the SpCas9 further comprises mutations that decrease nuclease activity selected from (i) D10A or D10N; and (ii) H840A, H840N or H840Y. Dependent 4-6 recite the encoded SpCas9 is further fused to a heterologous functional domain such as a transcriptional activation domain of VP64 or NF-kB p65. Independent claim 23 recite the variant SpCas9 of claim 1 encoded by a nucleic acid and that said nucleic acid is in vector, and in a mammalian host cell.
While the claims do not specifically recite that the fusion protein of claims 2-7 are found mammalian host cells, it would be an obvious variation that will be given the method claims are intended to utilize said variant SpCas9 in altering the genome of a cell, including mammalian cells.
Applicant’s Response and Examiner’s Rebuttal:
Applicant’s traverse the remaining non-statutory double patenting rejections of record.
Applicant’s traverse the six NSDP rejections of record for two reasons.
First, they argue the six patents are distinct for the following reasons. It is asserted that the Examiner has erred and utilized the specification rather than a claim by claim analysis and that this is not acceptable practice as the NSDP is to be controlled by claim by claim analysis only (See Remarks, pp. 5-7), . However, this is not accurate. MPEP 804(II)(B)(2)(a) states that the specification essentially can be utilized as a dictionary in order to determine the scope of various limitations in the claims. To this end, it would be prudent to determine the scope by which Applicant’s mean the generic term “host cell”. As noted, by Applicant’s themselves, the term host cell utilized throughout all of the specifications are to mean numerous different cells, both prokaryotic and eukaryotic, inclusive of mammalian host cells. Just because additional host cells would included does not dismiss or detract from the fact that they are envisioned explicitly to encompass mammalian cells as well as others.
With regard to Applicant’s assertions that MPEP 2144.08 that “The fact that a claimed species or subgenus is encompassed by a prior art genus is not sufficient by itself to establish a prima facie case of obviousness” (this in part II), does not negate the fact, as noted in part (I), if the prior art reference expressly discloses the claimed species, this is sufficient to establish prima facie obviousness. As noted above, and as actually highlighted by Applicant’s, the specifications do in fact stipulate the host cells are to include mammalian cells. As such, these express statements guiding one of skill in the art to what is in fact encompassed and defined to mean as “host cell” meets this express teaching.
In addition, Applicant’s arguments regarding what seems to be an enablement argument that the expectation of success of expressing a fusion protein in any host cell (citing Rai et al. from 2001), as is recited in the patented claims, makes the specific species of mammalian host cells as currently claimed non-obvious is also not convincing. It seems that Applicant’s are stating that one skilled in the art would have to actively figure out how to express a variant protein in the host cells of the claimed patents (See Remarks, p. 8, 1st paragraph). This is because, on the one hand, it would not be obvious that the patent claims proteins would be capable of expressing the claimed Cas9 proteins in any host cell, let alone the preferred ones of mammalian host cells. Again, this seems to be arguing that their own claims are not enabled. The Examiner counters, however, that expression of recombinant proteins and fusion proteins is routine and conventional in the art. And expressing proteins in mammalian host cells certainly is as well (For example, See Hopkins et al., Methods in Molecular Biology, 2012, Chapter 16 – cited herein).
Thus, Applicant’s arguments regarding distinctness of the claims is not convincing.
Second, Applicant’s continue to argue that the rejections are improper because of the patent term filing dates and the decisions made in Ex parte Baurin which relies heavily upon In re Allergen and the merits of the Patent Trial Appeal Board decision. However, as noted, the case in not precedential but is noted. As indicated in the Advisory action, the patent term dates are taken into consideration for certain situations (reversing the earlier interpretation that they were not). However, as noted, there are two separate justifications for double patenting. See In re Hubbell, 709 F. 3d 1140 (Fed. Cir. 2013) (“There are two justifications for obviousness-type double patenting. The first is ‘to prevent unjustified timewise extension of the right to exclude granted by a patent no matter how the extension is brought about.’ … The second rationale is to prevent multiple infringement suits by different assignees asserting essentially the same patented invention … this court reaffirmed the multiple assignee harassment rationale and applied it to a situation where, as here, the patents were related to the application only by way of a common inventor … ."). See also MPEP 804(II)(B) (“A rejection based on nonstatutory double patenting is based on a judicially created doctrine grounded in public policy so as to prevent the unjustified or improper timewise extension of the right to exclude granted by a patent … A double patenting rejection also serves public policy interests by preventing the possibility of multiple suits against an accused infringer by different assignees of patents claiming patentably indistinct variations of the same invention. In re Van Ornum, 686 F.2d 937, 944-48, 214 USPQ 761, 767-70 (CCPA 1982).”). So even assuming arguendo there is not an extension of patent rights as argued by Applicant’s, there still is the consideration of harassment by multiple owners.
In addition, the decisions in In re Allergen and Ex parte Baurin relied upon the fact that the application was “first patent ever” to issue for a specific invention. Clearly, the instant application is not the first patent ever to issue for the claimed invention. In Allergan, the court held that claims to the first patent ever to be filed covering a particular drug compound are not subject to nonstatutory double patenting over claims issued in a subsequently filed patent that shares a priority date with the first patent, even where those claims would expire later than the subsequently filed patent. Allergan, 111 F.4th at 1371. The court explained that is so because the first filed patent does not extend or prolong the monopoly beyond the period allowed by law; put differently it is not a “second, later expiring patent for the same invention.” Id. (citing Miller v. Eagle Mfg. Co., 151 U.S. 186, 198 (1894), and Abbvie, 764 F.3d at 1373). The Allergan court noted that “[a]s the first-filed, first-issued patent in its family, it is the patent that sets the maximum period of exclusivity for the claimed subject matter and any patentably indistinct variants.” Id. The Board in Baurin went further, however, and stipulated that it did not have actually issue from the same family at all.
For these reasons, the rejections of record are maintained.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 09 July 2026
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