DETAILED ACTION
Claims 1-68 were/stand cancelled. Claims 69-88 are pending.
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 .
Priority
This application claims benefit of 63/481,166 (01/23/2023) and is a CIP of 18/553,975 which is a 371 of PCT/US2022/023333 (04/04/2022) which claims benefit of 63/171,071 (04/05/2021) as reflected in the filing receipt issued on July 25 2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 7 2024, July 10 2025 and August 14 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 81 is objected to because of the following informalities: the word “group” is missing after diacyl and before “and a linker” in line 18 on page 5. Appropriate correction is required.
Claim Rejections - 35 USC § 112-Indefiteness
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 81 and 83-84 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.
MPEP 2173.05(p) states: 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). Here, claims 83-84 while being directed to a composition (a product) recite the active method step of “is delivered”. Thus, the claims are indefinite are they are a single claim directed both to a product and the method steps of using that product.
Claim 81 as currently written is vague and indefinite. The claim in the recitation of the degradable diacyl group indicates it has the structure of formula D-VII which includes Y3.
PNG
media_image1.png
645
1389
media_image1.png
Greyscale
It isn’t clear if that “or a group” is supposed to be an alternative choice for Y3 or if it is supposed to be an alternative choice for degradable diacyl group.
Claim 81 as currently written is vague and indefinite. The claim recites:
PNG
media_image2.png
212
1206
media_image2.png
Greyscale
however, there is no n in the formula. Therefore, it isn’t clear what n is referencing.
Claim 81 as currently written is vague and indefinite. In definition of Formula X there is an N but there is no definition of N. It is noted that this N is different than the lower-case n identified above.
PNG
media_image3.png
219
1276
media_image3.png
Greyscale
Claim 81 as currently written is vague and indefinite. The claim recites “wherein the repeating unit comprises a degradable diacyl and a linker but then the claim also recites wherein when the repeating unit comprises a linker. This seems to indicate that the linker is not required. This creates confusion as to the scope of the repeating unit.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 69-88 are rejected under 35 U.S.C. 103 as being unpatentable over Reyon et al. (USPGPUB No. 20170022507) in view of Cheng et al. (WO2020051223).
Applicant Claims
The instant application claims a composition comprising a lipid composition assembled with a nucleic acid editing system, wherein the nucleic acid editing system comprises i) a guide nucleic acid; (ii) a heterologous polypeptide comprising an endonuclease or a heterologous polynucleotide encoding the heterologous polypeptide comprising the endonuclease; and (iii) a donor template nucleic acid, wherein the lipid composition comprises a selective organ targeting (SORT) lipid, wherein the SORT lipid has a structural formula (S-I’) wherein the donor template nucleic acid is configured to alter a gene or transcript in a homology directed repair (HDR) pathway with a HDR repair rate of at least 25% when contacted with a plurality of cells.
As claimed the SORT lipid is DOTAP. As claimed the composition is configured to repair a cleaved cystic fibrosis transmembrane conductance regulator (CFTR) gene or transcript to yield a repaired CFTR gene or transcript encoding a functional CFTR protein when the composition is delivered to a plurality of cells, thereby enhancing an expression or activity of the functional CFTR protein in the plurality of cells.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Reyon et al. is directed to CRISPR/Cas related methods and compositions for treating cystic fibrosis. Claimed is a CRISPR/Cas system comprising a gRNA and a Cas9 molecule wherein the system is configured to correct a mutation at F508 of a cystic fibrosis transmembrane conductance regulator (CFTR) protein (claim 1). Taught is correcting a mutation in the CFTR gene by homology directed repair using a template nucleic acid (paragraph 1379). The template nucleic acid is used in conjugation with a Cas9 molecule and a gRNA molecule to alter the structure of a target position (paragraph 1402). Table 11B teaches gRNA which are for correcting a mutation in the CFTR gene. They include SEQ ID No 1598 (Table 10 B); SEQ ID NO: 409 (Table 11E) and SEQ ID NO: 1949 (Table 14C). Template nucleic acids include SEQ ID NO: 27270 (paragraph 1423); SEQ ID No: 27271 (paragraph 1426); SEQ ID NO: 27276 (paragraph 1435); and SEQ ID No: 27284 (paragraph 1499). It is taught that the components can be delivered lipids (paragraph 0304; 1702). Liposomes are taught which contain cationic lipids, natural helper lipids and polyethylene glycol conjugated lipids. Exemplary lipids include 1,2-dioleoyloxy-3-timethylammonium propate (DOTAP) (paragraph 1705-1707). Cells include basal cells, lung cells, etc. (paragraph 0300).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Reyon et al. teaches the combination of a gRNA/Cas9 and donor nucleic acid (template) and suggests DOTAP can be used to help deliver the complex and the complex is for correcting a mutation in the CFTR gene by homology directed repair, Reyon et al. does not teach the concentration of the lipids and consequently the degree of HDR repair rate.
Cheng et al. is directed to compositions and methods for organ specific delivery of nucleic acids. Claimed is a composition comprising (a) a therapeutic agent, and (b) a lipid nanoparticle comprising (1) a selective organ targeting compound; (2) an ionizable cationic lipid and (3) a phospholipid (claim 1). In come embodiments the compositions comprise a Cas9 protein, a single guide nucleic acid and a donor DNA (paragraph 0036; page 12). It is taught that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios (page 115, lines 2-10). It is taught that the lipid nanoparticle consist of five components including 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. The mole ratio of 5A2-SC8, cholesterol, DOP and DMG-PEG is fixed at 15:15:30:5 mol/mol. DOTNPX means DOTNP with different mole percentages of DOTAP (page 23, lines 22-25). Figure 44A shows indels% of upwards of 75%. Lung-targeted SORT LNPs edited 40% of epithelial cells and 65% of endothelial cells (page 93, lines 8-10). It is taught that given that epithelial cells are a primary target for correction of mutations in CFTR that cause cystic fibrosis, this result establishes lung-specific SORT LNPs as a compelling delivery system with immediate application for correcting CFTR mutations (page 100).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP.
Regarding the claimed SORT lipid of claim 69 and 72, both Reyon et al. and Cheng et al. suggest DOTAP.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claim 71, both Reyon et al. and Cheng et al. teach correcting mutations in CFTR.
Regarding claims 73-74, Cheng et al. teaches 5-60% DOTAP which is an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
While not claimed, the examiner notes that gRNA sequences taught in the instant specification (SEQ ID 1-3) have 100% identity to SEQ ID NO: 1598, 409 and 1949 respectfully of Reyon et al. See the alignment for instant SEQ ID NO: 1 below as an example:
PNG
media_image5.png
676
732
media_image5.png
Greyscale
While not claimed, the examiner notes that donor sequences SEQ ID: 4-10 taught in the instant specification have 100% identity with SEQ ID NO: 27270, 27271, 27276 and 27294 of Reyon et al. See alignment of SEQ ID NO:4 below as an example:
PNG
media_image6.png
783
713
media_image6.png
Greyscale
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 11229609 in view of Reyon et al. (USPGPUB No. 20170022507) and Cheng et al. (WO2020051223). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a composition comprising a lipid composition assembled with a nucleic acid editing system, wherein the nucleic acid editing system comprises i) a guide nucleic acid; (ii) a heterologous polypeptide comprising an endonuclease or a heterologous polynucleotide encoding the heterologous polypeptide comprising the endonuclease; and (iii) a donor template nucleic acid, wherein the lipid composition comprises a selective organ targeting (SORT) lipid, wherein the SORT lipid has a structural formula (S-I’) wherein the donor template nucleic acid is configured to alter a gene or transcript in a homology directed repair (HDR) pathway with a HDR repair rate of at least 25% when contacted with a plurality of cells.
Patent ‘609 claims a method for targeted delivery of a therapeutic agent to a non-liver organ or a non-liver cell therein in a subject in need thereof, the method comprising: administering to said subject said therapeutic agent assembled with a selective organ targeting (SORT) lipid composition that comprises: an ionizable cationic lipid; and a SORT lipid separate from said ionizable cationic lipid, which SORT lipid is selected from the group consisting of a cationic SORT lipid, a zwitterionic SORT lipid, and an anionic SORT lipid, wherein said SORT lipid composition is characterized by an apparent ionization constant (pKa) outside a range of about 6 to about 7 as determined by a 2-(p-toluidino)-6-naphthalenesulfonic acid titration assay, thereby providing a greater amount or activity of said therapeutic agent in said non-liver organ or said non-liver cell therein in said subject as compared to that achieved absent said SORT lipid. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid. As claimed, the therapeutic agent comprises a CRISPR associated Cas protein, a single guide RNA, etc.
While Patent ‘609 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ‘609 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
Reyon et al. is directed to CRISPR/Cas related methods and compositions for treating cystic fibrosis. Claimed is a CRISPR/Cas system comprising a gRNA and a Cas9 molecule wherein the system is configured to correct a mutation at F508 of a cystic fibrosis transmembrane conductance regulator (CFTR) protein (claim 1). Taught is correcting a mutation in the CFTR gene by homology directed repair using a template nucleic acid (paragraph 1379). The template nucleic acid is used in conjugation with a Cas9 molecule and a gRNA molecule to alter the structure of a target position (paragraph 1402). Table 11B teaches gRNA which are for correcting a mutation in the CFTR gene. They include SEQ ID No 1598 (Table 10 B); SEQ ID NO: 409 (Table 11E) and SEQ ID NO: 1949 (Table 14C). Template nucleic acids include SEQ ID NO: 27270 (paragraph 1423); SEQ ID No: 27271 (paragraph 1426); SEQ ID NO: 27276 (paragraph 1435); and SEQ ID No: 27284 (paragraph 1499). It is taught that the components can be delivered lipids (paragraph 0304; 1702). Liposomes are taught which contain cationic lipids, natural helper lipids and polyethylene glycol conjugated lipids. Exemplary lipids include 1,2-dioleoyloxy-3-timethylammonium propate (DOTAP) (paragraph 1705-1707). Cells include basal cells, lung cells, etc. (paragraph 0300).
Cheng et al. is directed to compositions and methods for organ specific delivery of nucleic acids. Claimed is a composition comprising (a) a therapeutic agent, and (b) a lipid nanoparticle comprising (1) a selective organ targeting compound; (2) an ionizable cationic lipid and (3) a phospholipid (claim 1). In come embodiments the compositions comprise a Cas9 protein, a single guide nucleic acid and a donor DNA (paragraph 0036; page 12). It is taught that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios (page 115, lines 2-10). It is taught that the lipid nanoparticle consist of five components including 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. The mole ratio of 5A2-SC8, cholesterol, DOP and DMG-PEG is fixed at 15:15:30:5 mol/mol. DOTNPX means DOTNP with different mole percentages of DOTAP (page 23, lines 22-25). Figure 44A shows indels% of upwards of 75%. Lung-targeted SORT LNPs edited 40% of epithelial cells and 65% of endothelial cells (page 93, lines 8-10). It is taught that given that epithelial cells are a primary target for correction of mutations in CFTR that cause cystic fibrosis, this result establishes lung-specific SORT LNPs as a compelling delivery system with immediate application for correcting CFTR mutations (page 100).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘609, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘609 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘609 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘609 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘609, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ‘609 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11304911 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘911 claims a method for non-liver targeted delivery of a therapeutic agent, the method comprising: administering to a subject in need thereof said therapeutic agent assembled with a selective organ targeting (SORT) lipid composition, which SORT lipid composition comprises: (i) an ionizable cationic lipid, and (ii) a SORT lipid separate from said ionizable cationic lipid, which SORT lipid is selected from the group consisting of a cationic SORT lipid, a zwitterionic SORT lipid, and an anionic SORT lipid; wherein, upon said administering, a surface of said SORT lipid composition interacts with apolipoprotein E (Apo E) to a lesser degree than with an endogenous protein that is not Apo E in said subject, thereby providing a lesser amount or activity of said therapeutic agent in liver or a cell therein in said subject as compared to that achieved absent said SORT lipid. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid. As claimed, the therapeutic agent comprises a CRISPR associated Cas protein, a single guide RNA, etc.
While Patent ‘911 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ‘911 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘911, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘911 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘911 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘911 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘911, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ‘911 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11510880 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘880 claims a composition comprising a lipid composition assembled with a therapeutic agent, which lipid composition comprises: an ionizable cationic lipid; and a cationic selective organ targeting (SORT) lipid separate from said ionizable cationic lipid, which lipid composition comprises said cationic SORT lipid in an amount sufficient to yield an apparent pKa of said lipid composition outside a range of about 6 to about 7, wherein said apparent pKa is determined by a 2-(p-toluidino)-6-naphthalenesulfonic acid titration assay. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid. As claimed, the therapeutic agent comprises a CRISPR associated Cas protein, a single guide RNA, etc.
While Patent ‘880 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ’880 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘880, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘609 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘880 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ’880 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘880, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ’880 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11590085 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘085 claims a method for targeted delivery of a gene or transcript editing composition to an organ or a cell therein, the method comprising: contacting said organ or said cell therein with said gene or transcript editing composition assembled with a selective organ targeting (SORT) lipid composition, wherein said SORT lipid composition comprises: (1) an ionizable cationic lipid; and (2) a SORT lipid selected from the group consisting of a cationic SORT lipid, a zwitterionic SORT lipid, and an anionic SORT lipid; thereby providing a modified expression profile of a target gene or transcript in said organ or said cell therein as compared to that achieved absent said SORT lipid. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid. As claimed, the therapeutic agent comprises a CRISPR associated Cas protein, a single guide RNA, etc.
While Patent ‘085 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ‘085 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘085, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘609 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘085 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘085 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘085, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ‘085 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11648210 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘210 claims a composition comprising a lipid composition assembled with a therapeutic agent, wherein the lipid composition comprises a cationic selective organ targeting (SORT) lipid in an amount sufficient to yield an apparent pKa of said lipid composition outside a range of about 6 to about 7. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid. As claimed, the therapeutic agent comprises a CRISPR associated Cas protein, a single guide RNA, etc.
While Patent ‘210 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ‘210 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘210, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘609 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘210 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘210 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘210, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ’210 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11648209 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘209 claims a composition for modifying a target gene or transcript in an organ or a cell therein, the composition comprising a gene or transcript editing composition assembled with a selective organ targeting (SORT) lipid composition, wherein the SORT lipid composition comprises an ionizable cationic lipid and a SORT lipid separate from the ionizable cationic lipid, wherein the SORT lipid is selected from the group consisting of a cationic SORT lipid, a zwitterionic SORT lipid, and an anionic SORT lipid; and wherein the gene or transcript editing composition comprises: (i) a polynucleotide-guided nuclease, or a polynucleotide comprising a sequence that encodes the polynucleotide-guided nuclease; and (ii) a guide polynucleotide configured to complex with at least a portion of the target gene or transcript in the organ or the cell therein, or a polynucleotide comprising a sequence that encodes the guide polynucleotide; and wherein the gene or transcript editing composition is non-naturally occurring. As claimed the composition further comprises a donor polynucleotide. The same SORT lipids are claimed. SORT lipid in 5 to 65% is claimed. The same sort lipids are claimed. As claimed the composition further comprises a phospholipid, a polymer-conjugated lipid, a steroid or steroid derivative, or a combination thereof separate from said SORT lipid.
While Patent ‘209 claims the same SORT lipid and a guide nucleotide, a nuclease and a donor nucleotide, Patent ‘209 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘209, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘209 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘209 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘209 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘209, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ‘209 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11766408 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘408 claims a composition comprising a SORT lipid composition assembled with a therapeutic agent, which SORT lipid composition comprises: (1) An ionizable cationic lipid; and (2) A permanently cationic selective organ targeting (SORT) lipid, wherein said SORT lipid composition comprises said permanently cationic SORT lipid at a molar percentage of about 5% or more, wherein the molar percentage is determined based on total mols of lipids present in the SORT lipid composition; wherein said SORT lipid composition is characterized by an apparent pKa of about 8 or higher as determined by a 2-(p-toluidino)-6-naphthalenesulfonic acid titration assay; and wherein said composition delivers said therapeutic agent to a lung or a lung cell following intravenous administration or inhalation; wherein (1) the ionizable cationic lipid is a compound having the structure of Formula (I) The same SORT lipid is claimed. Formula I is the same as instantly claimed Formula D-1. Cas proteins are claimed. A guide RNA is claimed.
While Patent ‘408 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Patent ‘408 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘408, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and Patent ‘408 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, Patent ‘408 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Patent ‘408 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘408, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Patent ‘408 and Reyon et al. teaches Cas9.
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 15-17, 20, 22-23, 25-28, 64, 68, 71-72, 82, 97 and 101-103 of copending Application No. 18419370 (USPGPUB No. 20240216515) in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘370 claims a method for delivery of a therapeutic agent to lung basal cells of a subject, comprising: intravenously administering to said subject a therapeutic agent assembled with a lipid composition that comprises:(i) an ionizable cationic lipid;(ii) a selective organ targeting (SORT) lipid separate from said ionizable cationic lipid (iii) a phospholipid;(iv) a steroid or steroid derivative; and(v) a polymer-conjugated lipid, wherein delivering said therapeutic agent to a lung of said subject provides an amount or activity of said therapeutic agent detectable in at least about 5% of basal cells in said lung of said subject. DOTAP is claimed. Cholesterol is claimed. 5A2-SC8 is claimed. A guide RNA and a CRISPR-associated (Cas) protein is claimed. The SORT is claimed from about 20 to about 65%.
While Copending ‘370 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, Copending ‘370 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘370, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and copending ‘370 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, copending ‘370 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Copending ‘370 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘370, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, copending ‘370 and Reyon et al. teaches Cas9.
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Regarding claims 80-81, 5A2-SC8 corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18529992 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘992 claims a composition comprising a lipid composition assembled with a therapeutic agent, wherein the lipid composition comprises a cationic selective organ targeting (SORT) lipid in an amount sufficient to yield an apparent pKa of said lipid composition outside a range of about 6 to about 7. The same SORT lipid is claimed. From about 5 to about 30% of SORT lipid is claimed. A phospholipid is claimed. A polymer conjugated lipid is claimed. Steroid or steroid derivative is claimed. A guide RNA and Cas protein are claimed.
While copending ‘992 claims the same SORT lipid and that the therapeutic agent can be a Cas protein and/or a single guide RNA, copending ‘992 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘992, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and copending ‘992 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed SORT lipid of claim 69 and 72, copending ‘992 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, copending ‘992 claims an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘992, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, copending ‘992 and Reyon et al. teaches Cas9.
Regarding claims 80-81, Cheng et al. teaches 5A2-SC8 which has the following structure (Fig. 20C):
PNG
media_image4.png
170
661
media_image4.png
Greyscale
this corresponds to a core of D-IV wherein c and d are 2, R6 is substituted alkyl, R3 and R4 are amino, D-VII wherein A1 and A2 are O, Y3 is C2 alkanediyl and R9 is C1 alkyl, in light of the indefiniteness above, the claim is interpreted as not requiring the linker, and the terminating group is D-VIII, Y4 is alkanediyl of C8 and R10 is H. This is also the same lipid used in the instant application examples (see Example 2).
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 62-81 of copending Application No. 18553975 (USPGPUB No. 20250281580). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘975 claims a method for enhancing an expression or an activity of a cystic fibrosis transmembrane conductance regulator (CFTR) protein in a cell, the method comprising:(a) contacting said cell with a nucleic acid editing system assembled with a lipid composition, wherein said nucleic acid editing system comprises (i) a guide nucleic acid, (ii) a heterologous polypeptide comprising an endonuclease or a heterologous polynucleotide encoding said heterologous polypeptide, and (iii) a donor template nucleic acid, wherein said contacting results in a complexing of said heterologous endonuclease with said guide nucleic acid in said cell; (b) cleaving a CFTR gene or transcript in said cell with said complex at a cleavage site to yield a cleaved CFTR gene or transcript; and (c) using said donor template nucleic acid to repair said cleaved CFTR gene or transcript to yield a repaired CFTR gene or transcript, thereby enhancing said expression or activity of CFTR protein in said cell. As claimed is step (c) (c) is characterized by an on-target repair rate of at least about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%. As claimed the lipid composition comprises an ionizable cationic lipid and a SORT lipid. The same dendrimers (i.e. Formula D-I and Formula X) are claimed. Same sort lipids are claimed. A steroid or steroid derivative, polymer conjugated lipid, and a phospholipid are claimed. A composition comprising the same is claimed. Cas9 polypeptide is claimed.
Therefore, the scopes of the copending claims and the instant application overlap and thus they are obvious variants of one another as both claim compositions comprising the same components (Cas9/guide nucleic acid and donor) in the same lipid composition.
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 140-159 of copending Application No. 18556614 (USPGPUB No. 20240207442 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘614 claims a method of performing homology directed repair (HDR) on a target gene in a population of cells, the method comprising contacting the population of cells with a composition comprising a lipid composition assembled with a gene or transcript editing composition, thereby resulting in a HDR correction rate of the target gene of at least 25%;wherein:(A) the gene or transcript editing composition comprises:(1) a polynucleotide comprising a sequence encoding a polynucleotide-guided nuclease;(2) a guide polynucleotide configured to complex with at least a portion of a target gene or transcript, or a polynucleotide comprising a sequence that encodes the guide polynucleotide; and(3) a donor polynucleotide configured to repair a modified target gene or transcript; and(B) the lipid composition comprises:(i) an ionizable cationic lipid having the structural Formula (D-I) or Formula (X);(ii) a steroid or steroid derivative;(iii) a phospholipid; and(iv) a polymer-conjugated lipid. Formula D-1 and Formula X are the same as instantly claimed. A cas9 protein is claimed.
Copending ‘614 does not claim a SORT lipid and does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘614, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids taught in Reyon et al. with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and copending ‘614 claims the therapeutic includes gRNA and Cas9.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Cheng et al. teaches an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘614, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, copending ‘614 and Reyon et al. teaches Cas9.
Regarding claims 80-81, copending ‘614 claims the same.
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-175 of copending Application No. 18724775 (USPGPUB No. 20260151350) in view of Reyon et al. and Cheng et al.
. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘775 claims a composition comprising a therapeutic agent assembled with a lipid composition, which lipid composition comprises: an ionizable cationic lipid; a polymer-conjugated lipid comprising one or more hydrocarbon chains that each comprise about 8 to about 20 carbon atoms; and a selective organ targeting (SORT) lipid separate from said ionizable cationic lipid and said polymer-conjugated lipid. wherein said lipid composition is characterized by an apparent ionization constant (pKa) from about 6 to about 7 as determined by a 2-(p-toluidino)-6-naphthalenesulfonic acid (TNS) titration assay. The ionizable cationic dendrimer has the same formula as instant formula X. The same SORT lipid is claimed. Therapeutic agents include a guide RNA and a CRISPR protein. Intravenous is claimed. A steroid or steroid derivative is claimed. A phospholipid is claimed.
While copending ‘775 claims the same SORT lipid and that the therapeutic agent can be a protein and a nucleic acid, copending ‘775 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘775, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and copending ‘775 claims the therapeutic includes nucleic acid and protein
Regarding the claimed SORT lipid of claim 69 and 72, copending ‘775 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Cheng et al. teaches an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘775, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, Reyon et al. teaches Cas9.
Regarding claims 80-81, copending ‘775 claims the same.
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Claims 69-88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of copending Application No. 19760572 in view of Reyon et al. and Cheng et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘572 claims a composition comprising:(A) a therapeutic agent; and(B) a lipid nanoparticle composition comprising:(1) a selective organ targeting compound;(2) an ionizable cationic lipid; and (3) a phospholipid; wherein the composition preferentially delivers the nucleic acid to a target organ selected from the lungs, the heart, the brain, the spleen, the lymph nodes, the bone marrow, the bones, the skeletal muscles, the stomach, the small intestine, the large intestine, the kidneys, the bladder, the breast, the liver, the testes, the ovaries, the uterus, the spleen, the thymus, the brainstem, the cerebellum, the spinal cord, the eye, the ear, the tongue, or the skin. The permanently cationic lipid is the same as the instantly claimed SORT lipid. The same dendrimer is claimed. A steroid is claimed. A PEGylated lipid is claimed. Therapeutic agents being a guide RNA. As claimed, the composition further comprises a protein such that the composition comprises both a protein and a nucleic acid.
While copending ‘572 claims the same SORT lipid and that the therapeutic agent can be a protein and a nucleic acid, copending ‘572 does not expressly claim the combination of a guide nucleic acid, Cas9, donor which could be used to repair a cleaved CFTR gene. However, these deficiencies are cured by Reyon et al. and Cheng et al.
The teachings of Reyon et al. and Cheng et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘572, Reyon et al. and Cheng et al. and utilize a combination of gRNA/Cas9 and template nucleic acids with lipid nanoparticles comprising 5A2-SC8, cholesterol, DOPE, DMG-PEG and DOTAP. One skilled in the art would have been motivated to utilize this composition in order to enhance gene editing as well as to allow for targeted delivery as taught by Cheng et al. One skilled in the art would have a reasonable expectation of success as Reyon et al. teaches that the gRNA/Cas9/template can be used with lipids such as DOTAP and copending ‘572 claims the therapeutic includes nucleic acid and protein
Regarding the claimed SORT lipid of claim 69 and 72, copending ‘572 claims the same.
Regarding the claimed repair rate in claim 69 and 70, Cheng et al. teaches editing efficiencies of 40% or greater. Cheng et al. teaches that increasing the incorporated DOTAP percentage from 5 to 60% resulted in CRISPR-guided gene editing from liver to lung 5A2-DOT-60 enabled mainly lung editing. This indicates that deep tissue editing can be achieved in a tissue-specific manner by adjusting the inner lipid component chemistry and molar ratios. Therefore, one skilled in the art would have been motivated to adjust not only the lipid components but their ratio to not only achieve the desired cell delivery but the degree of editing.
Regarding claims 73-74, Cheng et al. teaches an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 75-77, Reyon et al. teaches assays to determine the best stoichiometric ratio of gRNA:Cas protein (paragraph 1376). Cheng et al. teaches the protein and the nucleic acid are present in a molar ratio from about 1:1 to about 1:20 (paragraph 0035; page 12). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Copending ‘572, Reyon et al. and Cheng et al. and manipulate the amounts/ratios of the Cas9, gRNA and donor. One skilled in the art would have been motivated to manipulate the amounts in order to determine the optimal concentrations as suggested by Reyon et al.
Regarding claims 78-79, copending ‘572 and Reyon et al. teaches Cas9.
Regarding claims 80-81, copending ‘572 claims the same.
Regarding claim 82-84, firstly these claims are directed to cells which are not part of the composition. Furthermore, Reyon et al. teaches editing in lung and basal cells.
Regarding claim 85, Reyon et al. teaches intravenous administration (paragraph 0302).
Regarding claims 86-88, Cheng et al. teaches nanoparticles comprising 5A2-SC8, cholesterol (sterol), DOPE (phospholipid), DMG-PEG (polymer conjugated lipid) and DOTAP.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
Prosecution Insights