DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Response to Restriction Requirement filed 05 May 2026, Applicant did not amend the claims. Claims 1, 3-8, 17-23, 26-28 and 31-46, as previously amended on 11 September 2023, are pending.
Restriction/Election
The examiner acknowledges Applicant’s election without traverse of Group I. Accordingly, claims 35-36 and 45-46, which are directed to non-elected Group II, are withdrawn from consideration. 37 CFR 1.142(b).
The examiner acknowledges Applicant’s election without traverse of 93-O17O as the species of lipid-like compound encompassed by Formula (I) of claim 1 and/or claim 17. The chemical structure of 93-O17O is set forth below:
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Applicant states that “[c]laims 1, 3-6, 31, 32, and 35 read on the elected species.” Reply, p. 2.
The examiner additionally acknowledges Applicant’s elections without traverse of: (i) CRISPR/Cas9, as the species of protein, nucleic acid, or small molecule; and (ii) cancer, as the medical condition. Reply, p. 2.
Pursuant to 37 CFR 1.142(b), claims 7-8, 17-23, 26-28, 33-34, and 37-44 are withdrawn from consideration because they are directed to non-elected species.
Claims 1, 3-6, and 31-32 are considered below.
Search Extended
A search of the relevant prior art revealed that the elected compound (93-O17O) is novel and nonobvious. The examiner’s position is based primarily, but not exclusively, on the results of STN chemical structure searches conducted on 10 July 2026 for the present application and on 04 June 2024 in parent Application No. 16/966,368 (now Patent No. 12,133,855). MPEP § 803.02(III)(A) provides: “If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended.” For this purpose, the examiner identifies claim 6 as the most relevant Markush claim and notes that not all compounds encompassed by that claim are free of the prior art.
Claim Rejections - 35 U.S.C. 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, 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(a) 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.
Claims 1, 3-6, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Xu (US 2016/0009643 A1) in view of Tong (“Smart chemistry in polymeric nanomedicine." Chemical Society Reviews 43.20 (2014): 6982-7012) and Xu 2013 (“Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics.” Accounts of chemical research 46.7 (2013): 1647-1658).
Xu is directed to lipid-like disulfide compounds for the delivery of pharmaceutical agents. Title.
Xu discloses that the lipid-like compounds containing the disulfide bond are bioreducible and can form a nanocomplex with proteins, which allows for the safe and efficient delivery of therapeutic proteins to patients. Paras. [0005], [0017], [0021], [0023], [0031], [0044], and [0083].
Hydrophilic head group 2 disclosed in paragraph [0029] of Xu is consistent with hydrophilic head group 93 of claim 1. The linker groups disclosed in paragraph [0033] of Xu match those represented by variable X of claim 1. The ester moiety set forth in the middle of the first line of three exemplary linker groups is considered especially relevant. Paragraph [0034] of Xu exemplifies eight lipid-like compounds (lipidoids) comprising the foregoing ester linker coupled to disulfide hydrophobic tail groups. None of them includes hydrophilic head group 2. Instead, they respectively include hydrophilic head groups 1, 12, and 14, which — like hydrophilic head group 2 — are listed in paragraph [0029] of Xu. Nevertheless, a person having ordinary skill in the art would have readily envisaged modifying the lipidoids of paragraph [0034] by substituting hydrophilic head group 2 for hydrophilic head groups 1, 12, and/or 14. MPEP § 2131.02(III) (“A reference disclosure can anticipate a claim when the reference describes the limitations but ‘d[oes] not expressly spell out’ the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination.”), quoting Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015).
Formula (I) of Xu, which is disclosed in paragraph [0006], is relevant. The primary difference between Formula (I) of Xu and Formula (I) of claim 1 of the present application is as follows: In claim 1, variable m must be one (1) when and only when variable V is S (sulfur). See last line of claim 1. Thus, even when variable W is S, there is at least one carbon (e.g., a methylene group) between the sulfur of variable W and the sulfur of variable V. This operates to exclude the disulfide group (S–S) required by Formula (I) of Xu. It follows that none the eight disulfide compounds set forth in paragraph [0034] of Xu, as modified above by selecting hydrophilic head group 2, satisfies claim 1. As explained below, the following two references compensate for this deficiency: Tong and Xu 2013.
Tong is directed to smart chemistry in polymeric nanomedicine. Title.
Tong teaches that “[t]here exists a large difference in the redox potential between the mildly oxidizing extracellular milieu and the reducing environment of the intracellular fluids, such as the cytoplasm and the cell nucleus.” Page 3991. “This renders reduction-sensitive polymers particularly appealing for use in triggered release and other biomedical applications.” Id. “The disulfide bond has been extensively used to formulate many different polymeric particles (Scheme 5a).” (Emphasis added) Id. “For example, reduction-sensitive polymer–DNA complexes, polyion complex micelles, polymersomes, and degradable nanogels have been reported to achieve fast intracellular release of their cargo.” Id.
Tong additionally teaches as follows: “In addition to disulfide bonds, diselenide bonds have also shown promise as an oxidation and reduction responsive trigger due to their good activity in the presence of either type of environments (Scheme 5b). Selenium-containing compounds have been widely used in pharmacochemistry as antioxidants. To achieve dual redox responsiveness, a tri-block copolymer with one hydrophobic diselenide-containing block and two hydrophilic PEG blocks was synthesized and self-assembled into micelles in water. Diselenide bonds would undergo structural dissociation in the presence of oxidants (H2O2) or reductants (glutathione), and released drugs inside micelles. Additionally, a pH and dual redox responsive nanogel could be formulated based on PEG-b-poly-(L-glutamic acid) and diselenide bond crosslinking. In the presence of glutathione, an initial burst release of the encapsulated Doxo was followed by prolonged zero-order release over 48 hours, freeing 57% of the encapsulated drug.” (Emphasis added) Page 6992, left column.
Schemes 5(a) and 5(b) of Tong (page 6991), which are referred to above, are reproduced below:
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Xu 2013 is directed to selenium-containing Polymers: promising biomaterials for controlled release and enzyme mimics. Title.
Xu 2013 teaches that selenium resembles sulfur in chemical activity and physical properties. Page 1647, left column.
Xu 2013 teaches as follows: “Apart from beneficial biology effects, selenium also possesses unique chemical properties owing to its special electronegativity and atomic radius. The radius of the selenium atom is bigger than that of sulfur, and the electronegativity of selenium is weaker than that of sulfur.” Pages 1647-1648.
Xu 2013 teaches “[t]his leads to lower bond energy of C–Se and Se–Se than those of C–S and S–S (C–S 272 kJ mol-1; S–S 240 kJ mol-1; C–Se 244 kJ mol-1; Se–Se 172 kJ mol-1) and makes it easier for low valence state selenium compounds to be oxidized than low valence state sulfur compounds.” Page 1648, left column.
Xu 2013 teaches that “[d]ue to the unique redox property of selenium element, selenium-containing polymers have proven to be ideal candidates for responsive disassembly at mild conditions, which may be more benign for clinical use.” (Emphasis added) Page 1648, right column.
Before the effective filing date of the claimed invention, the teachings of Tong and Xu 2013 would have motivated a person having ordinary skill in the art to modify the lipidoids disclosed in Xu by substituting either a diselenide group or a C–Se group for the disulfide group. This modification would have been made for the purpose of yielding a lipidoid capable of forming a nanocomplex (e.g., with therapeutic proteins) having either (i) dual-redox responsiveness or (ii) the capability to trigger release of therapeutic proteins under even mild reductive intracellular environments. The foregoing modification would have been made with a reasonable expectation of success, especially considering (i) the similar but lower bond energies of C–Se and Se–Se, as compared to S–S; (ii) the teaching in Xu 2013 that Se bonds are more benign for clinical use than S bonds; and (iii) the primary reference, i.e., Xu, discloses that the hydrophobic tail can comprise selenium (para. [0031]). See also MPEP § 2144.09(I) (“rejection based on close structural similarity is founded on the expectation that compounds similar in structure will have similar properties”). Therefore, claims 1 and 3-6 are prima facie obvious.
Regarding claim 31, Applicant is referred to paragraphs [0017], [0023], and [0042] of Xu (the primary reference).
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of Tong and Xu 2013, as applied above to claims 1, 3-6 and 31, and further in view of Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although Xu teaches that the bioreducible lipidoids disclosed therein can form a nanocomplex with proteins (see, e.g., paras. [0017], [0021], [0023]), Xu is silent as to whether the protein CRISPR/Cas9 can be selected. Consequently, Xu does not satisfy claim 32. As explained below, Wang compensates for this deficiency.
Wang is directed to “[e]fficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” Title.
Wang teaches that “combining bioreducible lipid nanoparticles with negatively supercharged Cre recombinase or anionic Cas9:single-guide (sg)RNA complexes drives the electrostatic assembly of nanoparticles that mediate potent protein delivery and genome editing.” Abstract; see also pages 2872-73 at Conclusion. The examiner notes that “Cas9” is CRISPR-associated protein 9. Page 2871, left column.
The bioreducible lipids taught in Figure 2 of Wang (page 2869) are at least substantially identical to those disclosed in Xu (the primary reference). The examiner notes that amine head group 10 of Wang is identical to hydrophilic head group 2 of Xu, which is consistent with hydrophilic head group 93 of claim 1 of the present application.
Wang teaches: “These bioreducible lipids efficiently deliver protein cargo into cells, facilitate the escape of protein from endosomes in response to the reductive intracellular environment, and direct protein to its intracellular target sites. The delivery of supercharged Cre protein and Cas9:sgRNA complexed with bioreducible lipids into cultured human cells enables gene recombination and genome editing with efficiencies greater than 70%.” Abstract.
Before the effective filing date of the claimed invention, the teachings of Wang would have motivated a person having ordinary skill in the art to select CRISPR/Cas9 as the protein cargo for the nanocomplex of Xu (as modified above by Tong and Xu 2013) in an effort to develop a gene-editing molecular system that is both highly efficient and more benign for clinical use (no disulfide bonds). Therefore, claim 32 is prima facie obvious.
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, 46USPQ2d 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.2d937, 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 CFR1.321(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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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. Aweb-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/process/file/efs/guidance/ eTD-info-I.jsp.
Claims 1, 3-6, and 31-32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of Patent No. 9,765,022 (issued September 19, 2017) in view of Tong (“Smart chemistry in polymeric nanomedicine." Chemical Society Reviews 43.20 (2014): 6982-7012), Xu 2013 (“Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics.” Accounts of chemical research 46.7 (2013): 1647-1658) and, optionally, Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: The compounds disclosed in the conflicting claims (the claims of the ’022 Patent) require a disulfide bond. This is the only difference between those compounds and the compounds defined in present claims 1 and 3-6. The teachings of Tong and Xu 2013 are discussed above, in the first rejection under 35 U.S.C. 103. That discussion is incorporated by reference into this double patenting rejection. Tong and Xu 2013, in combination, compensate for the deficiency in the conflicting claims by providing motivation to substitute either a diselenide group or a C–Se group for the disulfide group. This modification would have been made for the purpose of yielding a lipidoid capable of forming a nanocomplex (e.g., with therapeutic proteins) having either (i) dual-redox responsiveness or (ii) the capability to trigger release of therapeutic proteins under even mild reductive intracellular environments. The teachings of Wang, which are discussed above in the second rejection under 35 U.S.C. 103, compensate for any deficiency in the conflicting claims relating to present claim 32 by providing motivation to select CRISPR/Cas9 as the protein cargo.
Claims 1, 3-6, and 31-32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of Patent No. 10,792,328 (issued October 6, 2020) in view of Tong (“Smart chemistry in polymeric nanomedicine." Chemical Society Reviews 43.20 (2014): 6982-7012), Xu 2013 (“Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics.” Accounts of chemical research 46.7 (2013): 1647-1658) and, optionally, Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: The compounds disclosed in the conflicting claims (the claims of the ’328 Patent) require a disulfide bond. This is the only difference between those compounds and the compounds defined in present claims 1 and 3-6. The teachings of Tong and Xu 2013 are discussed above, in the rejection under 35 U.S.C. 103. That discussion is incorporated by reference into this double patenting rejection. Tong and Xu 2013, in combination, compensate for the deficiency in the conflicting claims by providing motivation to substitute either a diselenide group or a C–Se group for the disulfide group. This modification would have been made for the purpose of yielding a lipidoid capable of forming a nanocomplex (e.g., with therapeutic proteins) having either (i) dual-redox responsiveness or (ii) the capability to trigger release of therapeutic proteins under even mild reductive intracellular environments. The teachings of Wang, which are discussed above in the second rejection under 35 U.S.C. 103, compensate for any deficiency in the conflicting claims relating to present claim 32 by providing motivation to select CRISPR/Cas9 as the protein cargo.
Claims 1, 3-6, and 31-32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-16 of Patent No. 12,133,855 (issued November 5, 2024) in view of Tong (“Smart chemistry in polymeric nanomedicine." Chemical Society Reviews 43.20 (2014): 6982-7012), Xu 2013 (“Selenium-containing polymers: promising biomaterials for controlled release and enzyme mimics.” Accounts of chemical research 46.7 (2013): 1647-1658) and, optionally, Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: The compounds disclosed in the conflicting claims (the claims of the ’855 Patent) require a disulfide bond. This is the only difference between those compounds and the compounds defined in present claims 1 and 3-6. The teachings of Tong and Xu 2013 are discussed above, in the rejection under 35 U.S.C. 103. That discussion is incorporated by reference into this double patenting rejection. Tong and Xu 2013, in combination, compensate for the deficiency in the conflicting claims by providing motivation to substitute either a diselenide group or a C–Se group for the disulfide group. This modification would have been made for the purpose of yielding a lipidoid capable of forming a nanocomplex (e.g., with therapeutic proteins) having either (i) dual-redox responsiveness or (ii) the capability to trigger release of therapeutic proteins under even mild reductive intracellular environments. The teachings of Wang, which are discussed above in the second rejection under 35 U.S.C. 103, compensate for any deficiency in the conflicting claims relating to present claim 32 by providing motivation to select CRISPR/Cas9 as the protein cargo.
Claims 1, 3-6, and 31-32 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 61 and 69-80 of Application No. 17/909,260 alone or in view of Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: For example, the compounds defined in conflicting claim 80 of the ’260 Application overlap the compounds defined in claim 6 of the present application. The teachings of Wang, which are discussed above in the second rejection under 35 U.S.C. 103, compensate for any deficiency in the conflicting claims relating to present claim 32 by providing motivation to select CRISPR/Cas9 as the protein cargo. This is a provisional rejection because the conflicting claims have not been patented.
Claims 1, 3-6, and 31-32 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3-4, 10, 12, 17, 22-26, 28, 50-51, 56, 58-59, 67, 70, 84, 88, and 116 of Application No. 18/265,561 alone or in view of Wang (“Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles.” PNAS 113.11 (2016): 2868-2873).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: For example, the compounds collectively defined in conflicting claim 4 (imidazolyl head group) and conflicting claims 24-26 and 28 (linker+hydrophobic tail) of the ’561 Application overlap the compounds defined in claim 6 of the present application. The teachings of Wang, which are discussed above in the second rejection under 35 U.S.C. 103, compensate for any deficiency in the conflicting claims relating to present claim 32 by providing motivation to select CRISPR/Cas9 as the protein cargo. This is a provisional rejection because the conflicting claims have not been patented.
Conclusion
Claims 1, 3-6, and 31-32 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
16 July 2026
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
Prosecution Insights