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 .
Election/Restrictions
Applicant’s elections without traverse of a canine IL-1β target gene and a guide RNA sequence of SEQ ID NO:506 in the reply filed on 11/19/2025 are acknowledged. However, the species election requirement has been withdrawn.
Claims Status
Claims 2, 5-6, 8-9, 11-12, 14-15, 17-18, 20-21, 23-24, 28, 31, 33-35, 37-51, 55-74 is/are cancelled. Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 36, 52-54 is/are currently pending. Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 36, 52-54 is/are under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Fig. 31B depicts “the amino acid sequence of wild-type and truncated canine IL1A prior to (top) and after (bottom) CRISPR-mediated genome editing” (paragraph [0067]); however, neither the drawing nor the specification disclose the SEQ ID NOs corresponding to each sequence.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 30 and 32 are objected to because of the following informalities: the phrasing of claims 30 and 32 do not make clear that the RNA-guided nuclease (claim 30) or nucleic acid encoding the RNA-guided nuclease (claim 32) are selected from the group “an RNA-guided nuclease or a nucleic acid encoding an RNA-guided nuclease” in claim 1. Furthermore, the phrasing of claim 30 implies that a nucleic acid is an RPA-guided nuclease protein, and the phrasing of claim 32 implies that an RNA-guided nuclease protein is an mRNA. Appropriate correction is required. The examiner suggests the following:
30. The composition of claim 1, wherein the composition comprises the RNA-guided nuclease.
32. The composition of claim 1, wherein the composition comprises the nucleic acid encoding the RNA-guided nuclease, and wherein the nucleic acid is an mRNA.
Claim Interpretation
Claim 1 recites an intended use of the claimed product—a composition comprising a LNP comprising an RNA-guided nuclease and at least one guide RNA targeting an IL-1α or IL-1β gene. According to MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. The intended use recited in claim 1 does not appear to impart any structure to the claimed product. Therefore for the purpose of examination, claim 1 is directed to the recited LNP composition.
Claim Rejections - 35 USC § 112
112(a):
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 36, 52-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claims 1 and 54 recite the limitations “for treating a joint disease or disorder” (claim 54) and “for the treatment or prevention of a joint disease or condition” (claim 1). However, the disclosure only provides written description of arthritic conditions, including osteoarthritis (paragraph [0006]). While the specification states that the compositions can be used to treat any “joint disorders that are characterized by an inflammatory component” (paragraph [0006]), the specification does not disclose the use of the claimed compositions in methods to treat non-arthritic joint disorders characterized by inflammation, including but not limited to cancer (see Mantyh, 2013). As such, the disclosure does not provide written description for any joint disease or disorder or condition (such as cancer), and only provides sufficient written description for arthritic joint diseases, disorders, or conditions. As claims 3-4, 7, 10, 13, 16, 19, 22, 25-27, 29-30, 32, 36, 52-53 depend on claim 1 but do not further limit the “joint disease or condition” of claim 1 such that the claims are sufficiently described, these claims are also rejected for lack of sufficient written description.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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(s) 1, 3, 7, 26-27, 29, 30, 32, 36, 52-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao (2019, provided by Applicant with IDS filed 11/19/2025), in view of Chen (WO 2019113061 A1), and as evidenced by Nishimasu (2015) and NCBI GenBank XO4964.1 and AY137079.1.
Regarding claim 1, Zhao teaches a composition for the treatment of a joint disease (osteoarthritis, see Title, Abstract), comprising:
An RNA-guided nuclease (Cas9); and
At least one guide RNA (gRNA) targeting an IL-1β gene (Abstract—Methods; pages 3-5; Supplementary Fig. 3).
Zhao teaches that the Cas9 used is S. aureus Cas9 (page 2). Nishimasu teaches that the PAM sequence recognized by S. aureus Cas9 is 5’-NNGRRT-3’, wherein R is a purine (A/G) (page 1114). Zhao teaches that immediately downstream of the targeted sequence of IL-1β guide 1 is 5’-CTGGAT-3’ (Supplementary Fig. 3), which is an S. aureus PAM sequence (“CT”=”NN”, “GA”=”RR”).
Regarding claim 3, Zhao teaches a guide (IL-1β Guide sequence 1, of Supp. Fig. 3) which targets exon 4 of the murine IL-1β gene (see BLAST alignment between annotated murine gene sequence XO4964.1 and “IL-1β Guide sequence 1” of Zhao).
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Regarding claim 7, while Zhao teaches that the guide RNAs target mouse IL-1β gene, Zhao teaches that the results indicate that targeting the IL-1β gene is promising for treatment of osteoarthritis in humans (pages 5-6), rendering obvious the application of the Cas9-gRNA composition of Zhao in humans in addition to in mice. As such, it would have been obvious to an artisan to design sgRNAs to target the human IL-1β gene, particularly exon 4, instead of mouse IL-1β gene, in an application in humans, rendering obvious the recited gRNA targeting sequences targeting sequences in human IL1B exon 4 adjacent to an S. aureus Cas9 PAM sequence (e.g., instant SEQ ID NO:720, adjacent to PAM sequence GGGCTT, see BLAST alignment below to Homo sapiens IL1B gene AY137079.1).
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Regarding claims 26-27, Zhao teaches that the nuclease is S. aureus Cas9 (page 2).
Regarding claims 30 and 32, Zhao teaches that the Cas9 is delivered encoded in a nucleic acid encapsulated in an AAV particle (Abstract—Methods), and is translated into a protein in cells (Abstract—Methods). Thus, Zhao teaches compositions comprising both the protein Cas9 and a nucleic acid encoding the protein Cas9.
Regarding claim 36, Zhao teaches that the guide RNA is a single guide RNA (sgRNA) (Supp. Fig. 3).
Regarding claim 53, Zhao teaches that the composition is formulated for intra-articular injection within a joint of a subject (Abstract—Methods).
Regarding claim 54, Zhao teaches a method of treating osteoarthritis (a joint disease), the method comprising:
Administering to a subject in need thereof, a composition comprising:
An RNA-guided nuclease or a nucleic acid encoding an RNA-guided nuclease; and
At least one guide RNA targeting an IL-1β gene, wherein the guide RNA specifically binds to a target sequence adjacent to a PAM sequence for the RNA-guided nuclease (Abstract—Methods; pages 3-6; Supp. Fig. 3).
However, Zhao does not teach that the Cas9-sgRNA system is delivered in a lipid nanoparticle (LNP), as required by the instant claims.
Chen teaches that Cas9-gRNA compositions can be delivered to subjects in vivo 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 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 also been obvious to such an artisan that, for the treatment of osteoarthritis, CRISPR therapeutics could be delivered intra-articularly, as in Zhao, 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 Zhao. As such, it would have been obvious to substitute the AAV vector of Zhao for the LNP of Chen, to substitute the wild-type Cas9 of Zhao 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 under 35 U.S.C. 103 as being unpatentable over Zhao (2019, provided by Applicant with IDS filed 11/19/2025) and Chen (WO 2019113061 A1), and as evidenced by Nishimasu (2015) and NCBI GenBank XO4964.1 and AY137079.1 as applied to claim 1 above, and further in view of Gabner (2018).
Zhao and Chen render obvious the limitations of claim 1, as described above. However, Zhao teaches a method of treating osteoarthritis wherein the gRNA targets murine IL1B and rendering obvious gRNA targeting human IL1B, but does not teach nor suggest 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 method of Zhao 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 method of Zhao to treat canine, feline, and equine osteoarthritis, wherein the method of Zhao treats osteoarthritis in mice by targeting gRNA to exon 4 of murine IL1B gene. This obvious variation of the methods and compositions of Zhao would render obvious instant SEQ ID NOs:217-235 (claim 13), 256-262 (claim 19), and 891-920 (claim 25).
Claim(s) 1, 3, 7, 27, 30, 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schmedt (WO 2020257504 A1), in view of Chen (WO 2019113061 A1).
Regarding claims 1, 3, and 7, Schmedt teaches a composition comprising an RNA-guided nuclease (Cas9) and a guide RNA comprising a targeting sequence of SEQ ID NO:683 (SEQ ID NO:683 is 100% identical to instant SEQ ID NO:188, see alignment below) (claims 1, 4, 12-15).
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Regarding claim 27, Schmedt teaches that the Cas9 protein can be S. pyogenes Cas9 or S. aureus Cas9 (paragraph [0012]).
Regarding claims 30 and 32, Schmedt teaches that the Cas9 may be delivered as a ribonuclear protein complex or encoded in a nucleic acid (paragraph [0079]).
However, Schmedt does not teach lipid nanoparticles comprising the CRISPR composition, merely that lipids or viral vectors may be used for delivery to cells (paragraphs [0078]-[0079]).
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claim 1, 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]).
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. As such, it would have been obvious to use lipid nanoparticles to deliver to cells the Cas9-gRNA compositions of Schmedt instead of viral vectors.
Claim(s) 1, 3-4, 26-27, 30, 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cooper (WO 2019232425 A1), in view of Chen (WO 2019113061 A1).
Regarding claims 1, 3, and 4, Cooper teaches a composition comprising an RNA-guided nuclease (Cas9) and a guide RNA comprising a targeting sequence of SEQ ID NO:613, targeting the human IL1A gene (SEQ ID NO:613 is 100% identical to instant SEQ ID NO:168, see alignment below) (Table 10; claims 1, 6-12, 25).
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Regarding claim 26, Cooper teaches that the RNA-guided nuclease is Cas9 (claims 8-12).
Regarding claim 27, Cooper teaches that the Cas9 is SpCas9 (S. pyogenes) (paragraph [0395]).
Regarding claims 30 and 32, Cooper teaches that the Cas9 endonuclease can be delivered encoded in mRNA or as a protein (claims 9-11).
However, Cooper does not teach lipid nanoparticles comprising the CRISPR composition; Cooper teaches that the CRISPR composition is delivered using a viral vector (paragraph [0161]).
Chen teaches that Cas9-gRNA compositions can be delivered to cells packaged in LNPs.
Regarding claim 1, 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]).
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. As such, it would have been obvious to use lipid nanoparticles to deliver to cells the Cas9-gRNA compositions of Cooper instead of viral vectors.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cooper (WO 2019232425 A1) and Chen (WO 2019113061 A1), as applied to claims 1 and 3 above, and further in view of Mata (2014).
Cooper and Chen render obvious the limitations of claim 1, as discussed above. However, Cooper teaches that the gRNA target is human IL-1α, not canine IL-1α.
Mata teaches that dogs (canines) are ideal models for testing CAR-T cell therapies.
Regarding claim 10, Mata teaches that dogs are ideal models for testing CAR-T cell therapies (Abstract; page 407). As Cooper teaches that the targeting of IL-1α by the CRISPR system is performed in CAR-T cells in order to mitigate “cytokine release syndrome and/or CAR-T associated neuropathy” (paragraph [003] of Cooper), it would have been obvious to an artisan at the time of filing that canine CAR-T cells should be modified for use in a canine model of the CAR-T therapy taught by Cooper. In order to design such a modified canine CAR-T cell, an artisan would recognize that the gRNA sequence should be modified to target canine IL-1α instead of human IL-1α. As such, it would have been obvious to an artisan to design a gRNA targeting canine IL1A exon 4, such as instant SEQ ID NO:202, as Cooper teaches a gRNA targeting human IL1A exon 4.
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, 36, 53-54 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).
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.
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 applied to claim 1 above, and further in view of Gabner (2018).
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, 36, 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).
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).
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 applied to claim 1 above, and further in view of Gabner (2018).
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).
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.
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 applied to claim 1 above, and further in view of Gabner (2018).
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).
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.
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 applied to claim 1 above, and further in view of Gabner (2018).
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).
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).
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 applied to claim 1 above, and further in view of Gabner (2018).
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.
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).
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.
Conclusion
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/RAM R SHUKLA/ Supervisory Patent Examiner, Art Unit 1635