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 .
Amendments
In the reply filed 5/15/2026, Applicant has amended Claims 17-18, 74-79, and cancelled claim 71.
Claims 17-18, 20, 26, 30, 69-70, 72-83 are under consideration.
Withdrawn 35 USC § 112(a)
The prior rejection of Claims 75-79 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn in light of Applicant’s amendments of Claim 75 to limit the length to the region complementary to the guide RNA.
Withdrawn 35 USC § 112(b)
The prior rejection of Claims 18, and 76-78 under 35 U.S.C. § 112(b) pre-AIA 2nd paragraph as being indefinite is withdrawn in light of Applicant’s amendments of Claim 18 to remove the trademarked Endo-porter, and Claims 76-78 to clarify sequence identity.
Allowable subject matter
Claims 76-79 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 2nd paragraph, set forth in this Office action below. Specifically, the prior art is silent to sgRNAs that target the RIP140 gene comprising at least 90% sequence identity to SEQ ID NOs:1-4.
New Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 76-79 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 76 recites the broad recitation of editing or deleting a “target gene”, and the claim also recites SEQ ID NOs:1-4 which is the narrower statement of the limitation as targeting the RIP140 gene. Applicant is recommended to amend the method to editing or deleting the RIP140 gene, as well as allowing the complex to edit or delete the RIP140 gene.
Withdrawn 35 USC § 103
The prior rejection of Claims 17, 69, 70, 72, and 74 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016, published 10/13/2016, see IDS filed 4/18/2023) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20, which is a limitation Guay does not teach.
The prior rejection of Claims 18, 26, and 83 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016), in view of Summerton et al., (ANYAS, 2005, 1058:62-75, see IDS filed 4/18/2023) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20.
The prior rejection of Claim 20, 72 and 73 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078), in view of Czech et al. (US 2005/0261223, filed 3/07/2005, published 11/24/2005, see IDS filed 4/18/2023) and Zhang (US 2016/0175462, filed 12/16/2015) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20.
The prior rejection of Claim 30 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078) in view of Summerton et al., (ANYAS, 2005, 1058:62-75), as applied to claims 17 and 18, in further view of Czech et al. (WO2014134509, filed 2/28/2014, published 9/04/2014, see IDS filed 4/18/2023) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20.
The prior rejection of Claims 80 and 81 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016), in view of Furch et al. (US 2018/0140717, filed 4/29/2016, see IDS filed 4/18/2023) and Mokhtarzadeh et al. (TIAC, 2016, 82:316-327, see IDS filed 4/18/2023) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20.
The prior rejection of Claims 80 and 82 under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016), in view of Colletti et al. (WO2015/069587, filed 11/03/2014, see IDS filed 4/18/2023) and Mokhtarzadeh et al. (TIAC, 2016, 82:316-327, see IDS filed 4/18/2023) is withdrawn in light of Applicant’s amendment of Claim 17 to limit the amphipathic helical peptide to SEQ ID NOs: 5-20.
New 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 17, 69, 70, 72, and 74-75 are rejected under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016, published 10/13/2016, see IDS filed 4/18/2023) in view of Summerton et al., (US 2006/0014667, filed 9/20/2004, published 1/19/2006).
LHKLLHHLLHHLHKLLHHLHHLLHKL (SEQ ID NO: 6) embodiments
In regard to claim 17, Guay teaches methods of using synthetic peptides for transducing cargo to target cells (Abstract, Summary). Guay et al. teaches a composition comprising:
A nucleic acid-guided endonuclease such as CRISPR/Cas9,
A sequence-specific targeting nucleic acid such as a guide RNA, and
An amphipathic helical peptide,
wherein the Cas9 and gRNA and the amphipathic helical peptide form a complex, and
wherein the amphipathic helical peptide mediates delivery of the complex to a target cell and wherein the Cas9 endonuclease mediates editing or deletion of target gene in the target cell ([0008-0025, 0029-0030, 0098-0102, 0287-0306]).
However, although Guay teaches a genus of amphipathic helical peptides and variants thereof, they are silent to the amphipathic helical peptide of SEQ ID NO: 6.
Summerton teaches amphipathic helical peptides for the delivery of cargo to cells, wherein a preferred amphipathic helical peptide is LHKLLHHLLHHLHKLLHHLHHLLHKL (see Fig. 9c), which is 100% identical to SEQ ID NO: 6.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method comprising a Cas nuclease and gRNA, and amphipathic helical peptide as taught by Guay and substitute the preferred amphipathic helical peptide that corresponds to instant SEQ ID NO:6 as taught by Summerton with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Summerton because of the preferred distribution of three “strong-base” lysines increases binding and penetration of the cell membrane for cargo delivery with reduced cytotoxicity compared to other delivery peptides [0006, 0058, 0076].
In regard to claims 69 and 70, as stated supra, Guay et al. teaches the amphipathic helical peptide mediated delivery of the Cas9/guide RNA complex to the cell to mediate editing of the target gene.
In regard to claim 72, Guay teaches the target cell is mammalian [0037, 0169, 0173, 0187, 0191, 0292, 0303])
In regard to claims 74 and 75, as stated supra, Guay et al. teaches a Cas9 guide RNA, and provides working examples of crRNA with 30 nucleotide spacer domains that target genes immediately adjacent to a “NGG” PAM motif (Example 13, [0291, 0297, 0304].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 20, 72 and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078), in view of Summerton et al., (US 2006/0014667), as applied to claim 17, in further view of Czech et al. (US 2005/0261223, filed 3/07/2005, published 11/24/2005, see IDS filed 4/18/2023) and Zhang (US 2016/0175462, filed 12/16/2015, prior art of record).
As discussed previously, Guay et al. suggest a method for gene editing in a cell comprising a CRISPR/Cas9 nuclease, gRNA, and amphipathic helical peptide in a complex delivered to the target cell.
However, although Guay teaches the method of modifying cells are suitable for clinical or therapeutic uses in a variety of cell types [0030-0031, 0167], they are silent with respect to targeting the RIP140 gene in adipocytes.
Czech et al. teaches methods for targeting RIP140 in adipocytes ([0167], Fig. 6-8).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method for targeting a gene in a cell as taught by Guay and choose the RIP140 gene in adipocytes as taught by Czech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Czech because inhibiting RIP140 in adipocytes potentiates insulin action on glucose transport into these cells, thereby providing a means to treat disorders associated with aberrant glucose transport such as diabetes (Abstract, [0011, 0172]). In regard to the reasonable expectation of success in making and using a guide RNA for the CRISPR/Cas9 systems of Guay, Zhang et al. (US2016/0175462) teaches making and using guide RNA to target a variety of genes, including RIP140 (alias NRIP1, see Table C), and discloses a web-based software tool to guide the selection and validation of target sequence [0268].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 80 and 81 are rejected under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078), in view of Summerton et al., (US 2006/0014667), as applied to claim 17, in further view of of Furch et al. (US 2018/0140717, filed 4/29/2016, see IDS filed 4/18/2023) and Mokhtarzadeh et al. (TIAC, 2016, 82:316-327, see IDS filed 4/18/2023).
As discussed previously, Guay et al. suggest a method for gene editing in a cell comprising a CRISPR/Cas9 nuclease, gRNA, and amphipathic helical peptide in a complex delivered to the target cell.
However, Guay is silent with respect to an aptamer based cell targeting ligand conjugated to the amphiphilic peptide.
Furch teaches a methods of modifying a cell comprising CRISPR/Cas9 nuclease, gRNA in a nanocarrier and cell targeting ligand (Abstract, [0045]). In regard to claim 80, Furch teaches the targeting ligand is an aptamer (Abstract, [0007, 0015, 0028, 0056]). In regard to claim 81, Furch teaches the targeting ligand is non-covalently embedded in the nanocarrier and discloses the use of targeting anchors for doing so [0028, 0040, 0056].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method comprising a Cas nuclease, gRNA, and amphipathic helical peptide as suggested by Guay and combine an aptamer based cell targeting ligand non-covalently embedded in the complex as taught by Furch with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Furch because the targeting ligand may direct the composition to a particular cell type and reduces off-target toxicity [0011]. In regard to choosing an aptamer as the targeting ligand, Mokhtarzadeh teaches that using aptamers for targeting nanocarriers would have been obvious because although they exhibit the affinities and specificities similar to monoclonal antibodies, they are easier to produce and show efficient uptake because of their small size (Introduction, p. 317).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 80 and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078), in view of Summerton et al., (US 2006/0014667), as applied to claim 17, in further view of of Colletti et al. (WO2015/069587, filed 11/03/2014, see IDS filed 4/18/2023) and Mokhtarzadeh et al. (TIAC, 2016, 82:316-327, see IDS filed 4/18/2023).
As discussed previously, Guay suggests a method for gene editing in a cell comprising a CRISPR/Cas9 nuclease, gRNA, and amphipathic helical peptide in a complex delivered to the target cell.
However, Guay is silent with respect to an aptamer based cell targeting ligand conjugated to the amphiphilic peptide.
Colletti et al. teaches methods comprising a nucleic acid such as a siRNA, an amphipathic helical peptide and cell targeting ligand (Abstract, Description of the Invention, p. 3, Peptides, pgs. 19-20, Targeting Ligands, pgs. 70-71, Table 2). In regard to claim 80, Colletti teaches the targeting ligand is an aptamer (p. 70, last para.). In regard to claim 82, Colletti teaches the targeting ligand (L) is conjugated to the peptide (P) (Abstract, Summary of the Invention).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method comprising a Cas nuclease, gRNA, and amphipathic helical peptide as taught by Guay and combine an aptamer based cell targeting ligand conjugated to the peptide as taught by Colletti with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Colletti because the targeting ligand may direct the composition to a particular cell type (p. 70, 2nd para.). In regard to choosing an aptamer as the targeting ligand, Mokhtarzadeh teaches that using aptamers for targeting nanocarriers would have been obvious because although they exhibit the affinities and specificities similar to monoclonal antibodies, they are easier to produce and show efficient uptake because of their small size (Introduction, p. 317).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 17, 18, 26, 30, 69, 70, 72, 74-75 and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Guay et al. (US 2016/0298078, filed 4/18/2016, published 10/13/2016, see IDS filed 4/18/2023) in view of Czech et al. (WO2014134509, filed 2/28/2014, published 9/04/2014, see IDS filed 4/18/2023)
LHLLHHLLHHLHHL (SEQ ID NO: 10) embodiments
In regard to claims 17 and 18, Guay teaches methods of using synthetic peptides for transducing cargo to target cells (Abstract, Summary). Guay et al. teaches a composition comprising:
A nucleic acid-guided endonuclease such as CRISPR/Cas9,
A sequence-specific targeting nucleic acid such as a guide RNA, and
An amphipathic helical peptide comprising an endosome leakage domain,
wherein the Cas9 and gRNA and the amphipathic helical peptide form a complex, and
wherein the amphipathic helical peptide mediates delivery of the complex to a target cell and wherein the Cas9 endonuclease mediates editing or deletion of target gene in the target cell ([0008-0025, 0029-0030, 0098-0102, 0287-0306]).
However, although Guay teaches a genus of amphipathic helical peptides and variants thereof, they are silent to the amphipathic helical peptide of SEQ ID NO:10.
Czech et al. teaches methods of using a composition comprising a sequence-specific targeting nucleic acid, and an amphipathic helical peptide to transduce a cell (Abstract). In regard to the amphipathic helical peptide, Czech teaches a short 14-amino acid amphipathic helical delivery peptide (i.e., sDP(14)) of “LHLLHHLLHHLHHL” (see SEQ ID NO:6 on p. 23, p. 74, last para. & see SEQ ID NO:39 on p. 75, p. 76, Example 4), which is 100% identical to SEQ ID NO: 10.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method comprising a Cas nuclease and gRNA, and amphipathic helical peptide as taught by Guay and substitute the 14-amino acid amphipathic helical peptide that corresponds to instant SEQ ID NO:10 as taught by Czech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Czech because the short 14-amino acid peptides have reduced immunogenicity compared to the longer peptides ( (p. 20, 2nd para., p. 63, 3rd para.).
In regard to claim 26, as stated supra, Guay et al. teaches the Cas9 endonuclease.
In regard to claim 30, in one embodiment Czech teaches a sequence-specific targeting nucleic acid (i.e, siRNA) and an amphipathic helical peptide (i.e., Endo-Porter) form a complex that is encapsulated in a glucan shell (p. 80, last para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method comprising a Cas nuclease, gRNA, and the short 14-amino acid amphipathic helical peptide as suggested by Guay et al. and further combine a glucan shell as taught by Czech with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Czech because the glucan shell protects the RNA based cargo in the blood stream and gut (p. 64, 5th para., p. 90, 2nd para.).
In regard to claims 69 and 70, as stated supra, Guay et al. teaches the amphipathic helical peptide mediated delivery of the Cas9/guide RNA complex to the cell to mediate editing of the target gene.
In regard to claim 72, Guay teaches the target cell is mammalian [0037, 0169, 0173, 0187, 0191, 0292, 0303])
In regard to claims 74 and 75, as stated supra, Guay et al. teaches a Cas9 guide RNA, and provides working examples of crRNA with 30 nucleotide spacer domains that target genes immediately adjacent to a “NGG” PAM motif (Example 13, [0291, 0297, 0304].
In regard to claim 83, Guay specifically teaches the S. pyogenes Cas9 ([0287], see SEQ ID NO: 74 of Guay).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 5/15/2026 are acknowledged.
Applicant argues that claim 17 was amended to incorporate the limitations of claim 18, which was amended to remove Endo-porter as the amphipathic helical peptide.
Applicant's arguments have been fully considered and they are found persuasive. However, Guay has been reapplied in view of Summerton or Czech, which make obvious the amphipathic helical peptides of SEQ ID NOs:10 and 6, respectively
Withdrawn Double Patenting
The prior rejection of Claims 17-18, 20, 26, 30, 69-74, 80-83 on the grounds of nonstatutory double patenting over claims 1-14 of U.S. Patent No. 11,519,009 (Czeh et al., Patented 12/06/2022) is withdrawn in light of Applicant’s corrected filing receipt changing instant application to a divisional of cited patent.
Objection to the Specification
The disclosure is objected to because of the following informalities: [0001] of the specification filed 10/26/2022 indicates that instant application is a continuation of application 16/463,646, now US Patent 11,519,009, but in light of Applicant’s corrected filing receipt, it should be indicated as a divisional.
Appropriate correction is required.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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