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 05/04/2026 has been received and considered entered. This is a response to amendments and arguments filed 05/06/2026.
Claims Status
Claims 2, 5-6, 8-9, 11-12, 14-15, 17-18, 20-21, 23-24, 28, 31, 33-51, 55-74 is/are cancelled. Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 52-54 is/are currently pending. Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 52-54 is/are under examination.
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.
Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 52-53 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. This is a new grounds of rejection necessitated by amendment.
MPEP 2173.05(p) states the following:
A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). In Katz, a claim directed to "[a] system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data" was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318, 97 USPQ2d at 1749 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited "an input means" and required a user to use the input means was found to be indefinite because it was unclear "whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means."); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph).
Claim 1 recites a composition (“A composition for the treatment or prevention of an IL-1α-mediated or IL-1β-mediated inflammatory joint disease or condition”) and a method step (“wherein the one or more LNP deliver the single sgRNA species”). This renders claim 1 indefinite. Claims 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 52-53 depend on and require all of the limitations of claim 1 but do not rectify this indefiniteness, and so are also rendered indefinite.
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.
US 11033590 B2:
Claims 1, 3, 4, 26-27, 30, 32, 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 10-14 of U.S. Patent No. 11033590 B2 in view of Chen (WO 2019113061 A1) as evidenced by Otero (2007). This rejection is maintained.
The issued claims teach a pharmaceutical composition “for the treatment or prevention of a joint disease or condition, comprising: a CRISPR system comprising a Cas9 protein and at least one guide RNA targeting an IL-1β gene or IL-1α gene (claims 1, 3-5, 10, 14). The intended use of the recited pharmaceutical compositions being “for the treatment of a joint disease or condition” renders obvious a method of treating a joint disease or condition using the recited pharmaceutical compositions. Claims 1 and 10 require that the pharmaceutical composition be administered by “injection of the pharmaceutical composition into the joint”, rendering obvious that the pharmaceutical composition is formulated for intra-articular injection into a joint, as required by instant claim 53. As the issued claims recite that the target of the gRNA is exon 4 of a human IL-1β or IL-1α gene, any candidate sequence in the human IL-1α and IL-1β genes is rendered obvious, including instant SEQ ID NOs:168-201, 298-496, and 681-740, of instant claims 4 and 7. The issued claims also recite that the composition should be injected into a joint (claim 1), which inherently comprises chondrocytes, synoviocytes, synovial macrophages, synovial fibroblasts (see Otero).
However, the issued claims do not recite lipid nanoparticles comprising the CRISPR composition; the issued claims recite that the CRISPR composition is delivered using a viral vector (claims 1, 6-10, 15-18). The issued claims also do not recite that the Cas9 is an enhanced specificity variant Cas9 protein, that the gRNA is an sgRNA, or that the composition is formulated for parenteral administration.
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claims 1 and 54, Chen teaches that CRISPR therapeutics, including nucleic acids encoding Cas9 and gRNAs, can be delivered packaged in LNPs, as an obvious alternative to viral vectors (paragraphs [00285], [00287], [00307]).
Regarding claim 29, Chen teaches that “Nickase variants of CRISPR enzymes, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing” (paragraph [00202]).
Regarding claim 36, Chen teaches that guide RNAs can be single guide RNAs, preferentially (paragraphs [0022], [0040], [0068], [0095]).
Regarding claim 52, Chen teaches that CRISPR therapeutics for the treatment of osteoarthritis (paragraph [00327]) could be delivered intra-articularly or parenterally (paragraph [00313]).
It would have been obvious to an artisan at the time of filing that lipid nanoparticles were well-known in the art as an alternative to viral vectors as delivery vehicles for CRISPR therapeutics, based on the teachings of Chen. It would have been obvious to an artisan at the time of filing that single guide RNAs were well known in the art and a common formulation for guide RNAs in CRISPR-Cas9 systems. It would have also been obvious to such an artisan that, for the treatment of osteoarthritis, CRISPR therapeutics could be delivered intra-articularly, as in the issued claims, or parenterally, for systemic administration, based on the teachings of Chen. It would have further been obvious to such an artisan that enhanced-specificity variants of Cas9 proteins were well-known in the art and would provide the benefit of enhanced specificity relative to wild-type Cas9 proteins, as used in the issued claims. As such, it would have been obvious to substitute the AAV vector of the issued claims for the LNP of Chen, to substitute the wild-type Cas9 of the issued claims with an enhanced-specificity variant Cas9 as taught by Chen, and to administer the CRISPR therapeutic parenterally instead of intra-articularly, as obvious formulation and administration variants.
Claim(s) 13, 19, 25 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 11033590 B2 and Chen (WO 2019113061 A1) as evidenced by Otero (2007), as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the issued claims and Chen are discussed above and can be combined to render obvious claim 1. Furthermore, the issued specification teaches that the “joint disorder or condition” recited in the claims encompasses osteoarthritis (col. 1 lines 18-25).
However, the issued claims recite gRNA targeting human IL1A and IL1B, but do not recite gRNA targeting canine, feline, or equine IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claims 13, 19, and 25, it would have been obvious to an artisan at the time of filing that the compositions of the issued claims could be used to treat osteoarthritis in non-murine and non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of canine, feline, and equine IL1B genes in order to use the composition of the issued claims to treat canine, feline, and equine osteoarthritis, wherein the composition of the issued claims as recited can be used to treat joint disorders including osteoarthritis in humans by targeting gRNA to a human IL1B gene. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:217-235 (claim 13), 256-262 (claim 19), and 891-920 (claim 25).
US 11324838 B2:
Claims 1, 3-4, 7, 10, 13, 16, 19, 26-27, 29-30, 32, 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14-18 of U.S. Patent No. 11324838 B2 in view of Chen (WO 2019113061 A1) as evidenced by Otero (2007). This rejection is maintained.
The issued claims recite methods of treating arthritis in a subject, the method comprising administering to a joint of the subject a pharmaceutical composition comprising a nucleic acid encoding a Cas9 protein and a nucleic acid encoding a guide RNA targeting an IL-1α or IL-1β gene, wherein the target sequence is adjacent to a PAM sequence (claim 1). The issued claims recite that the subject is a canine, equine, or human, rendering obvious that the target gene is canine, equine, or human IL-1α or IL-1β (claims 3-5). As such, all gRNA target sequences adjacent to a PAM sequence in the human, canine, and equine IL1A and IL1B are rendered obvious (including the sequences recited in instant claims 4, 7, 10, 13, 16, and 19). The issued claims recite that the composition is administered through intra-articular injection, rendering obvious that the composition is formulated for intra-articular injection. The issued specification teaches that “Cas9” encompasses both S. pyogenes and S. aureus Cas9 (col. 25 lines 16-19). The issued claims also recite that the composition should be injected into a joint (claim 6), which inherently comprises chondrocytes, synoviocytes, synovial macrophages, synovial fibroblasts (see Otero).
However, the issued claims do not recite that the Cas9 is an enhanced specificity variant Cas9 protein, that the gRNA is an sgRNA, that the composition is formulated for parenteral administration, or that the composition is packaged in an LNP (the issued claims recite that the composition is packaged in a viral vector, see claims 1, 11-13).
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claims 1 and 54, Chen teaches that CRISPR therapeutics, including nucleic acids encoding Cas9 and gRNAs, can be delivered packaged in LNPs, as an obvious alternative to viral vectors (paragraphs [00285], [00287], [00307]).
Regarding claim 29, Chen teaches that “Nickase variants of CRISPR enzymes, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing” (paragraph [00202]).
Regarding claim 36, Chen teaches that guide RNAs can be single guide RNAs, preferentially (paragraphs [0022], [0040], [0068], [0095]).
Regarding claim 52, Chen teaches that CRISPR therapeutics for the treatment of osteoarthritis (paragraph [00327]) could be delivered intra-articularly or parenterally (paragraph [00313]).
It would have been obvious to an artisan at the time of filing that lipid nanoparticles were well-known in the art as an alternative to viral vectors as delivery vehicles for CRISPR therapeutics, based on the teachings of Chen. It would have been obvious to an artisan at the time of filing that single guide RNAs were well known in the art and a common formulation for guide RNAs in CRISPR-Cas9 systems. It would have also been obvious to such an artisan that, for the treatment of osteoarthritis, CRISPR therapeutics could be delivered intra-articularly, as in the issued claims, or parenterally, for systemic administration, based on the teachings of Chen. It would have further been obvious to such an artisan that enhanced-specificity variants of Cas9 proteins were well-known in the art and would provide the benefit of enhanced specificity relative to wild-type Cas9 proteins, as used in the issued claims. As such, it would have been obvious to substitute the AAV vector of the issued claims for the LNP of Chen, to substitute the wild-type Cas9 of the issued claims with an enhanced-specificity variant Cas9 as taught by Chen, and to administer the CRISPR therapeutic parenterally instead of intra-articularly, as obvious formulation and administration variants.
Claim(s) 25 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 11324838 B2 and Chen (WO 2019113061 A1) as evidenced by Otero (2007), as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the issued claims and Chen are discussed above and can be combined to render obvious claim 1.
However, the issued claims recite gRNA targeting human, canine, and equine IL1A and IL1B, but do not recite gRNA targeting feline IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claim 25, it would have been obvious to an artisan at the time of filing that the compositions of the issued claims could be used to treat osteoarthritis in non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of feline IL1B genes in order to use the composition of the issued claims to treat feline osteoarthritis, wherein the composition of the issued claims as recited can be used to treat joint disorders including osteoarthritis in humans, canines, and equines by targeting gRNA to a human, canine, or equine IL1B gene, respectively. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:891-920 (claim 25).
US 12290572 B2:
Claims 1, 3-4, 7, 10, 13, 16, 19, 26-27, 29-30, 32, 36, 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-12, 14-20 of U.S. Patent No. 12290572 B2 in view of Chen (WO 2019113061 A1) as evidenced by Otero (2007). This rejection is maintained.
The issued claims recite a pharmaceutical composition comprising a nucleic acid encoding a Cas9 protein (S. pyogenes or S. aureus) and a nucleic acid encoding a guide RNA targeting an IL-1α gene or IL-1β gene (claims 1, 4-5, 11, 14-15). The IL-1α and IL-1β genes are human, canine, or equine IL-1α or IL-1β genes (claims 6-8, 16-18), rendering obvious any gRNA targeting sequences adjacent to a PAM sequence, including instant SEQ ID NOs:168-262, 298-590, 681-860 (instant claims 4, 7, 10, 13, 16, 19). The pharmaceutical compositions are formulated for parenteral or intra-articular injection (claims 9-10, 19-20). The issued claims recite that the pharmaceutical compositions are “for the treatment or prevention of a joint disease or condition”, rendering obvious a method of treating or preventing a joint disease or condition using the recited pharmaceutical compositions. The issued claims also recite that the composition should be injected into a joint (claim 10), which inherently comprises chondrocytes, synoviocytes, synovial macrophages, synovial fibroblasts (see Otero).
However, the issued claims do not recite that the Cas9 is an enhanced specificity Cas9 variant protein, that the gRNA is an sgRNA, or that the CRISPR composition is comprised in an LNP.
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claims 1 and 54, Chen teaches that CRISPR therapeutics, including nucleic acids encoding Cas9 and gRNAs, can be delivered packaged in LNPs, as an obvious alternative to viral vectors (paragraphs [00285], [00287], [00307]).
Regarding claim 29, Chen teaches that “Nickase variants of CRISPR enzymes, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing” (paragraph [00202]).
Regarding claim 36, Chen teaches that guide RNAs can be single guide RNAs, preferentially (paragraphs [0022], [0040], [0068], [0095]).
It would have been obvious to an artisan at the time of filing that lipid nanoparticles were well-known in the art as an alternative to viral vectors as delivery vehicles for CRISPR therapeutics, based on the teachings of Chen. It would have been obvious to an artisan at the time of filing that single guide RNAs were well known in the art and a common formulation for guide RNAs in CRISPR-Cas9 systems. It would have further been obvious to such an artisan that enhanced-specificity variants of Cas9 proteins were well-known in the art and would provide the benefit of enhanced specificity relative to wild-type Cas9 proteins, as used in the issued claims. As such, it would have been obvious to substitute the AAV vector of the issued claims for the LNP of Chen, and to substitute the wild-type Cas9 of the issued claims with an enhanced-specificity variant Cas9 as taught by Chen, as obvious variants and simple substitutions.
Claim(s) 25 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 12290572 B2 and Chen (WO 2019113061 A1) as evidenced by Otero (2007), as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the issued claims and Chen are discussed above and can be combined to render obvious claim 1.
However, the issued claims recite gRNA targeting human, canine, and equine IL1A and IL1B, but do not recite gRNA targeting feline IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claim 25, it would have been obvious to an artisan at the time of filing that the compositions of the issued claims could be used to treat osteoarthritis in non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of feline IL1B genes in order to use the composition of the issued claims to treat feline osteoarthritis, wherein the composition of the issued claims as recited can be used to treat joint disorders including osteoarthritis in humans, canines, and equines by targeting gRNA to a human, canine, or equine IL1B gene, respectively. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:891-920 (claim 25).
US 12419968 B2:
Claims 1, 3-4, 7, 10, 13, 16, 19, 26-27, 29-30, 32, 36, 52-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 412, 14-20 of U.S. Patent No. 12419968 B2 in view of Chen (WO 2019113061 A1) as evidenced by Otero (2007). This rejection is maintained.
The issued claims recite a pharmaceutical composition comprising a nucleic acid encoding a Cas9 protein (S. pyogenes or S. aureus) and a nucleic acid encoding a guide RNA targeting an IL-1α gene or IL-1β gene (claims 1, 4-5, 11, 14-15). The IL-1α and IL-1β genes are human, canine, or equine IL-1α or IL-1β genes (claims 6-8, 16-18), rendering obvious any gRNA targeting sequences adjacent to a PAM sequence, including instant SEQ ID NOs:168-262, 298-590, 681-860 (instant claims 4, 7, 10, 13, 16, 19). The pharmaceutical compositions are formulated for parenteral or intra-articular injection (claims 9-10, 19-20). The issued claims recite that the pharmaceutical compositions are “for the treatment or prevention of a joint disease or condition”, rendering obvious a method of treating or preventing a joint disease or condition using the recited pharmaceutical compositions. The issued claims also recite that the composition should be injected into a joint (claim 10), which inherently comprises chondrocytes, synoviocytes, synovial macrophages, synovial fibroblasts (see Otero).
However, the issued claims do not recite that the Cas9 is an enhanced specificity Cas9 variant protein, that the gRNA is an sgRNA, or that the CRISPR composition is comprised in an LNP.
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claims 1 and 54, Chen teaches that CRISPR therapeutics, including nucleic acids encoding Cas9 and gRNAs, can be delivered packaged in LNPs, as an obvious alternative to viral and other non-viral delivery vehicles (paragraphs [00285], [00287], [00307]).
Regarding claim 29, Chen teaches that “Nickase variants of CRISPR enzymes, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing” (paragraph [00202]).
Regarding claim 36, Chen teaches that guide RNAs can be single guide RNAs, preferentially (paragraphs [0022], [0040], [0068], [0095]).
It would have been obvious to an artisan at the time of filing that lipid nanoparticles were well-known in the art as an alternative to viral vectors as delivery vehicles for CRISPR therapeutics, based on the teachings of Chen. It would have been obvious to an artisan at the time of filing that single guide RNAs were well known in the art and a common formulation for guide RNAs in CRISPR-Cas9 systems. It would have further been obvious to such an artisan that enhanced-specificity variants of Cas9 proteins were well-known in the art and would provide the benefit of enhanced specificity relative to wild-type Cas9 proteins, as used in the issued claims. As such, it would have been obvious to substitute the liposome of the issued claims for the LNP of Chen, and to substitute the wild-type Cas9 of the issued claims with an enhanced-specificity variant Cas9 as taught by Chen, as obvious variants and simple substitutions.
Claim(s) 25 is/are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 12419968 B2 and Chen (WO 2019113061 A1) as evidenced by Otero (2007), as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the issued claims and Chen are discussed above and can be combined to render obvious claim 1.
However, the issued claims recite gRNA targeting human, canine, and equine IL1A and IL1B, but do not recite gRNA targeting feline IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claim 25, it would have been obvious to an artisan at the time of filing that the compositions of the issued claims could be used to treat osteoarthritis in non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of feline IL1B genes in order to use the composition of the issued claims to treat feline osteoarthritis, wherein the composition of the issued claims as recited can be used to treat joint disorders including osteoarthritis in humans, canines, and equines by targeting gRNA to a human, canine, or equine IL1B gene, respectively. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:891-920 (claim 25).
18005544:
Claims 1, 3-4, 7, 10, 13, 26-27, 29-30, 32, 36, 52-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 9, 13, 17, 27, 30-33, 38, 42, 47, 51-54, 65 of copending Application No. 18005544 in view of Chen (WO 2019113061 A1) as evidenced by Otero (2007). This rejection is maintained.
The copending claims recite methods of treating arthritis in a subject, the method comprising administering to a joint of the subject a pharmaceutical composition comprising a nucleic acid encoding a Cas9 protein (S. pyogenes or S. aureus) and a nucleic acid encoding a guide RNA targeting an IL-1α or IL-1β gene, wherein the target sequence is adjacent to a PAM sequence (claims 1, 27, 31-33, 65). The copending claims recite that the target gene is a canine or human IL1A or IL1B gene (claims 1, 5, 9, 13, 17, 31, 38, 42, 47, 51). The copending claims recite that the composition is administered through intra-articular injection and is formulated for intra-articular injection (claims 30, 52). The joint inherently comprises chondrocytes, synoviocytes, synovial macrophages, synovial fibroblasts (see Otero).
However, the copending claims do not recite that the Cas9 is an enhanced specificity variant Cas9 protein, that the gRNA is an sgRNA, that the composition is formulated for parenteral administration, or that the composition is packaged in an LNP (the copending claims recite that the composition is packaged in a liposome, see claims 25, 63).
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claims 1 and 54, Chen teaches that CRISPR therapeutics, including nucleic acids encoding Cas9 and gRNAs, can be delivered packaged in LNPs, as an obvious alternative to viral and other non-viral vectors (paragraphs [00285], [00287], [00307]).
Regarding claim 29, Chen teaches that “Nickase variants of CRISPR enzymes, for example Cas9, can be used to increase the specificity of CRISPR-mediated genome editing” (paragraph [00202]).
Regarding claim 36, Chen teaches that guide RNAs can be single guide RNAs, preferentially (paragraphs [0022], [0040], [0068], [0095]).
Regarding claim 52, Chen teaches that CRISPR therapeutics for the treatment of osteoarthritis (paragraph [00327]) could be delivered intra-articularly or parenterally (paragraph [00313]).
It would have been obvious to an artisan at the time of filing that lipid nanoparticles were well-known in the art as an alternative to viral vectors and other non-viral vectors as delivery vehicles for CRISPR therapeutics, based on the teachings of Chen. It would have been obvious to an artisan at the time of filing that single guide RNAs were well known in the art and a common formulation for guide RNAs in CRISPR-Cas9 systems. It would have also been obvious to such an artisan that, for the treatment of osteoarthritis, CRISPR therapeutics could be delivered intra-articularly, as in the copending claims, or parenterally, for systemic administration, based on the teachings of Chen. It would have further been obvious to such an artisan that enhanced-specificity variants of Cas9 proteins were well-known in the art and would provide the benefit of enhanced specificity relative to wild-type Cas9 proteins, as used in the copending claims. As such, it would have been obvious to substitute the liposome of the copending claims for the LNP of Chen, to substitute the wild-type Cas9 of the copending claims with an enhanced-specificity variant Cas9 as taught by Chen, and to administer the CRISPR therapeutic parenterally instead of intra-articularly, as obvious formulation and administration variants.
This is a provisional nonstatutory double patenting rejection.
Claim(s) 19, 25 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18005544 and Chen (WO 2019113061 A1) as evidenced by Otero (2007), as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the copending claims and Chen are discussed above and can be combined to render obvious claim 1.
However, the copending claims recite gRNA targeting human and canine IL1A and IL1B, but do not recite gRNA targeting feline or equine IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claim 25, it would have been obvious to an artisan at the time of filing that the compositions of the copending claims could be used to treat osteoarthritis in non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of feline or equine IL1B genes in order to use the composition of the issued claims to treat feline or equine osteoarthritis, wherein the composition of the copending claims as recited can be used to treat joint disorders including osteoarthritis in humans and canines by targeting gRNA to a human or canine IL1B gene, respectively. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:256-262, 831-860, 891-920 (claims 19, 25).
This is a provisional nonstatutory double patenting rejection.
18856005:
Claims 1, 3-4, 7, 10, 13, 26-27, 29-30, 32, 36, 52-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 32, 34-40, 42-44, 70 of copending Application No. 18856005 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. This rejection is maintained.
The copending claims recite a pharmaceutical composition and a method of treating diseases comprising administering to a subject the pharmaceutical composition, wherein the pharmaceutical composition comprises LNPs comprising an RNA-guided nuclease or a nucleic acid encoding an RNA-guided nuclease, and at least one guide RNA or nucleic acid encoding at least one guide RNA, wherein the gRNA targets IL1A or IL1B (claims 1-2, 32, 34, 70). The copending claims recite that the nuclease is an S. pyogenes Cas9 (claims 35-37) or a specificity-enhanced esCas9, hfCas9, peCas9, or ARCas9 (claim 38). The copending claims recite that the gRNA is an sgRNA (claim 42). The copending claims recite that the target gene is a human or canine gene (claims 43-44). The copending claims recite that the composition is administered, encompassing any method of administration, including parenteral and intra-articular (claim 70; see specification paragraphs [00803]-[00804], the administration methods encompassed by copending claim 70 encompass parenteral and intra-articular administration). The copending claims recite a method of treating any disease, encompassing joint diseases (claim 70; paragraph [0002] of the specification teaches that the recited “disease or disorder” of claim 70 encompasses joint diseases).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim(s) 19, 25 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18856005, as applied to claim 1 above, and further in view of Gabner (2018). This rejection is maintained.
The teachings of the copending claims are discussed above and render obvious instant claim 1.
However, the copending claims recite gRNA targeting human and canine IL1A and IL1B, but do not recite gRNA targeting feline or equine IL1B genes.
Gabner teaches that osteoarthritis “affects most mammalian species, including humans, horses, dogs, cats and sheep, all of which exhibit a similar pathogenesis” (page 2). Furthermore, Gabner teaches that IL-1β is “one of the key arthritogenic triggers” (page 2). Thus, regarding claims 19 and 25, it would have been obvious to an artisan at the time of filing that the compositions of the copending claims could be used to treat osteoarthritis in non-human mammalian species, such as dogs, cats, and horses. It therefore would have been obvious to design gRNA targeting exon 4 of feline or equine IL1B genes in order to use the composition of the issued claims to treat feline or equine osteoarthritis, wherein the composition of the copending claims as recited can be used to treat joint disorders including osteoarthritis in humans and canines by targeting gRNA to a human or canine IL1B gene, respectively. This obvious variation of the methods and compositions of the issued claims would render obvious instant SEQ ID NOs:256-262, 831-860, 891-920 (claims 19, 25).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 05/04/2026 have been fully considered but they are not persuasive. Applicant has argued that the issued and copending claims and Chen do not teach or obviate delivery of LNPs to the recited cell types of instant claim 1. However, the issued and copending claims recite intra-articular administration of pharmaceutical compositions (into the joint), which, as taught by Otero, inherently comprise the cell types recited in instant claim 1. Furthermore, Chen teaches that LNPs can be administered to a wide variety of tissues in a variety of methods, including intra-articular injection. As such, the combination of the issued and copending claims and Chen obviate intra-articular injection of LNPs comprising the CRISPR-Cas composition, which inherently includes administration to chondrocytes, synoviocytes, synovial macrophages, and synovial fibroblasts.
Conclusion
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.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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