DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1, 2, 7, 12, 20, 23, and 24 are pending.
Claims 5, 15, 25-38, 41, 49, 51, 52, 55, 58, 71, and 73 are withdrawn.
Claims 3, 4, 6, 8-11, 13, 14, 16-19, 21, 22, 39, 40, 42-48, 50, 53, 54, 56, 57, 59-70, 72, 74, and 75 are cancelled.
Elected Species - Free of Prior Art
As elected by applicants in the response to the species restriction requirement dated 30 June 2025, the species of the compound ATX-193, see below
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where R1 and R2 are each independently (CH3(CH2)m)2CH-, m is 6, L1 and L2 are each independently a linear C3 alkylene, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0, appears to be free of prior art. This species reads on claims 1, 2, 7, 12, 20, 23, and 24. As a result, the species of
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of claims 1, 2, 7, 12, 20, 23, and 24 appears to be free of prior art.
The closest prior art is Ansell et al. (US20150005363, published 01 January 2015, hereinafter Ansell). Ansell teaches a cationic lipid compound of Formula (I), see below,
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, see Paras. [0007]-[0026];[0074]-[0075], the compound of Formula (I) is of subformula (III), see below,
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, see Para. [0036], where Z1 and Z2 are represented by Formula II, see below
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, where R8 and R9 are each independently C3-C8 alkyl, see Para. [0035] and Claim 10, [i.e., Formula (II) including R8 and R9 correspond to instant application variables R1 and R2, which include m is 4-11], and X and Y are each, independently —(CH2)c— and each occurrence of c is, independently, 2-10, i.e., 2, 3, 4, 5, 6, 7, 8, 9, or 10, see Paras. [0025];[0031]; Claim 7, i.e., X, Y, and c correspond to instant application variables L1 and L2, which include a linear C1-5 alkylene].
Ansell does not specifically emphasize together in one specifically synthesized and/or one specifically shown chemical structure the claim 1 limitations of instant application variables of m is 4-11 combined with L1 and L2 are each independently a linear C1-5 alkylene, specifically the elected species limitations of instant application variables m is 6 and L1 and L2 are each independently a linear C3 alkylene. The closest specific compounds to ATX-193 of Ansell are Compound 13 and Compound 20 with both requiring modification to select the optimal number of -CH2- groups for R8, R9, X, and Y to obtain the elected species
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, see Paras. [0194];[0218] and the bottom of Pg. 46. Since Ansell teaches a vast number of possible variables associated with Formula (I) leading to significate choices of variables to arrive at Compounds 13 and 20, Ansell lacks a finite number of identified, predictable solutions for a person of ordinary skill in the art before the effective filing date of the claimed invention to have good reason to rely upon the known options of Ansell to modify Compounds 13 and 20 to produce the elected species of ATX-193 with predictable results and an expectation of success.
Restriction Requirement
Claim 24 is free of prior art. The restriction requirement among the species of claim 24, as set forth in the Office action mailed on 28 July 2025, has been reconsidered in view of the lack of prior art of claim 24 to the elected species pursuant to MPEP § 821.04(a). The restriction requirement is hereby withdrawn as to any claim that requires all the limitations of a free of prior art claim species which is currently only claim 24. Specifically, the restriction requirement of 28 July 2025 is withdrawn for claim 24 and the restriction requirement still applies to claims 1, 2, 5, 7, 12, 15, 20, 23, 25-38, 41, 49, 51, 52, 55, 58, 71, and 73. Claims 5, 15, and 25-32 directed to Group I having differing variables from the free of prior art species and claims 33-38, 41, 49, 51, 52, 55, 58, 71, and 73 directed to Groups II-III, remain withdrawn from consideration because they do not all require all of the limitations of the free of prior art species.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is free of prior art in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable, see In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971) and MPEP § 804.01.
Species Search Extension
As per MPEP 803.02C.2., the herein search and examination is extended to the non-elected species or group of species that falls within the scope of a proper Markush grouping that includes the elected species. The herein search is extended to the instant application claims 1, 2, 7, 12, 20, 23, and 24 variables of R1 and R2 are each independently (CH3(CH2)m)2CH-, m is 4-7, L1 and L2 are each independently a linear C2-5 alkylene, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0. Accordingly, claims 1, 2, 7, 12, 20, 23, and 24 have been examined on the merits herein. The withdrawal of Group I claims 5, 15, and 25-32 is maintained.
Response to Arguments
Applicant’s arguments filed 27 October 2025 have been fully considered where some are persuasive and some are not persuasive.
Applicant’s argue that Ansell does not disclose the limitations as recited in claim 1. These arguments have been considered and are persuasive as applied to the elected species ATX-193, but are not persuasive as applied to general Formula I for the reasons set forth in the modified for clarity grounds of rejection below and the response to arguments below.
Claim Rejections - 35 USC § 103
Applicant’s arguments with respect to elected species ATX-193 in the remarks filed on 27 October 2025 are sufficient to overcome the rejection of claims 1, 2, 7, 12, 20, 23, and 24 under 35 U.S.C. 103 as being unpatentable over Ansell et al. (US20150005363, cited by applicants as US9463247, 05 May 2022, hereinafter Ansell), with respect to the elected species ATX-193 only, the rejection is withdrawn.
Applicant’s arguments with respect to general Formula I in the remarks filed on 27 October 2025 are not sufficient to overcome the rejection of claims 1, 2, 7, 12, 20, 23, and 24 under 35 U.S.C. 103 as being unpatentable over Ansell et al. (US20150005363, cited by applicants as US9463247, 05 May 2022, hereinafter Ansell). Due to the withdrawal of the rejection with respect to the elected species ATX-193, a modified for clarity ground of rejection is provided below with respect to general Formula I.
In response to applicant’s arguments on pages 11-12 of the remarks filed on 27 October 2025, that “Formula (I) of Ansell is broad, and arriving at instant claim 1 would require specific selections from a broad range of substituents.” When there is motivation to solve a problem and there are a finite number of identified, predictable solutions to be tested for improved properties, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product is not of innovation but of ordinary skill and common sense, see KSR, 550 U.S. at 402-03, 82 USPQ2d at 1390 and MPEP 2143 I.E.
As stated on pages 5-7 of the previous office action dated 28 July 2025, Ansell teaches homolog Compound 13
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, Paras. [0007]-[0026];[0194]-[0197], the bottom of Pg. 46, and MPEP 2144.09. Compound 13 depicts m is 3 which differs from instantly claimed Formula I where m is 4-11. All other compound variables of the Ansell Compound 3 meet the variables in instantly claimed Formula I, where instant application variables R1 and R2 are each independently (CH3(CH2)m)2CH-, L1 and L2 are each independently a linear C5 alkylene, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0. Ansell further teaches the m variable is within R8 and R9 and may each independently be C3-C8 alkyl, where m is 2-7
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, see Para. [0035] and Claim 10. Ansell details seven possible choices of sufficiently close structural similarity for the instantly claimed m variable with all but 2 choices differing from the instantly claimed range. Seven possible alkyl chain choices in the Compound 13 m variable of sufficiently close structural similarity are within a finite number of alkyl chains to be tested for improved properties and predictability within the cationic lipid art leading to a reasonable expectations of success for those of ordinary skill in the art.
Ansell teaches homolog Compound 20
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, see Paras. [0218]-[0219], the bottom of Pg. 46, and MPEP 2144.09. Compound 20 depicts L1 and L2 are each independently linear C8 alkylene which differs from instantly claimed Formula I where L1 and L2 are each independently a linear C1-5 alkylene. All other compound variables of the Ansell Compound 20 meet the variables in instantly claimed Formula I, where instant application variables R1 and R2 are each independently (CH3(CH2)m)2CH-, m is 4, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0. Ansell further teaches the L1 and L2 variables are X and Y and may each independently be –(CH2)c-, where c is 2-10, see Paras. [0025];[0031] and Claim 7. Ansell details nine possible choices of sufficiently close structural similarity for the instantly claimed L1 and L2 variables with most of the choices within the instantly claimed range. Nine possible alkyl chain choices in the Compound 20 L1 and L2 variables of sufficiently close structural similarity are within a finite number of alkyl chains to be tested for improved properties and predictability within the cationic lipid art leading to a reasonable expectations of success for those of ordinary skill in the art.
For the reasons indicated above, applicant’s above arguments are not persuasive.
In response to applicant’s arguments on page 12 of the remarks filed on 27 October 2025, that “one of ordinary skill in the art may be motivated to select one of the best-performing compounds, such as Compound 4 or Compound 19, as a starting point for modification” instead of compounds 13 and 20 with “the highest ED50 reported as a starting point for modification”. It is noted “ED50” values are not instantly claimed.
The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), and MPEP 2143
Ansell teaches Compound 13 has a ED50 of >0.30 mg/kg and Compound 20 has an ED50 of 0.009 mg/kg
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, see Paras. [0248]-[0249], Bottom of Pg 46. Compound 20 with the more favorable ED50 value differs from Compound 13 by a -CH2- groups in the m position and L positions. Therefore, it would have been obvious for a person of ordinary skill in the art to modify Compound 13 of Ansell to have an additional -CH2- group in the m position or to modify Compound 20 of Ansell to have less -CH2- groups in the L positions before the effective filing date of the claimed invention to predictably test for a difference in the ED50 value based on the number of -CH2- groups in the m positions and L positions, see MPEP 2143 B & G and 2144.09.
For the reasons indicated above, applicant’s above arguments are not persuasive.
In response to applicant’s arguments on pages 12-13 of the remarks filed on 27 October 2025, that “the instantly claimed compounds can release encapsulated cargo and be cleared from a biological system more efficiently than the compounds of Ansell, and thus demonstrate unexpected improvements over the compounds of Ansell”. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious, see Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In addition, “[t]o establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range.” In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960), see MPEP 716.02(d). Applicant’s provide a comparison to Compound 19 of Ansell; however, Compound 19 of Ansell does not meet the limitations of instantly claimed Formula I and is not relied upon in the rejection of record for any teaching or matter specifically challenged in the argument.
As stated above, Compound 20 of Ansell showed an ED50 of 0.009 mg/kg, see above. Since a chemical composition and its properties are inseparable, see MPEP 2112.01 II., a person of ordinary skill in the art before the effective filing date of the claimed invention would predict the modified homolog of the Ansell Compound 20, as detailed above, would necessarily possess the same properties as currently argued.
For the reasons indicated above, applicant’s above arguments are not persuasive.
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, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Modified for clarity ground of rejection with respect to general
Formula I only
Claims 1, 2, 7, 12, 20, 23, and 24 stand rejected under 35 U.S.C. 103 as being unpatentable over Ansell et al. (US20150005363, published 01 January 2015, cited by applicants as US9463247, 05 May 2022, hereinafter Ansell).
Ansell teaches the claims 1, 2, 7, 12, 20, 23, and 24 limitations of a cationic lipid compound of Formula (I), see below,
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, see Paras. [0007]-[0026];[0074]-[0075], the compound of Formula (I) is of subformula (III), see below,
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, see Para. [0036], where Z1 and Z2 are represented by Formula II, see below
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, where R8 and R9 are each independently C3-C8 alkyl, see Para. [0035], [i.e., Formula (II) including R8 and R9 correspond to instant application variables R1 and R2, which include m is 4-11], and X and Y are each, independently —(CH2)c— and each occurrence of c is, independently, 2-10, i.e., 2, 3, 4, 5, 6, 7, 8, 9, or 10, see Paras. [0025];[0031],[i.e., X, Y, and c correspond to instant application variables L1 and L2, which include a linear C1-5 alkylene].
Therefore, Ansell teaches the instant application variable of m is 2-7 and the instant application variables of L1 and L2 are each independently a linear C2-10 alkylene.
Ansell does not specifically emphasize together in one specifically synthesized and/or one specifically shown chemical structure the claim 1 limitations of instant application variables of m is 4-11 combined with L1 and L2 are each independently a linear C1-5 alkylene.
Ansell teaches specific homologs of instant application Formula I, such as Compound 13
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, see Paras. [0007]-[0026];[0194]-[0197] and the bottom of Pg. 46, where instant application variables R1 and R2 are each independently (CH3(CH2)m)2CH-, m is 3, L1 and L2 are each independently a linear C5 alkylene, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0. Ansell compound 13 differs from the instant application Formula I, by the instant application m value. As stated above, Ansell teaches the instant application variable of m is 2-7; therefore, Compound 13 of Ansell modified to where m is 4 is a homolog to the instant application Formula I.
Ansell teaches homolog Compound 20
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, see Paras. [0218]-[0219] and the bottom of Pg. 46, where instant application variables R1 and R2 are each independently (CH3(CH2)m)2CH-, m is 4, L1 and L2 are each independently a linear C8 alkylene, R3 is a linear C3 alkylene, R4 and R5 are C1 alkyl, X is O, and n is 0. Ansell compound 20 differs from the instant application Formula I, by the instant application L1 and L2 value. As stated above, Ansell teaches the instant application variable of L1 and L2 are each independently a linear C2-10 alkylene; therefore, Compound 20 of Ansell modified to where L1 and L2 are each independently a linear C3 alkylene is a homolog to the instant application Formula I.
Since homologs or compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups, are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties, see MPEP 2144.09, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified Ansell to select the optimal number of -CH2- groups for R8, R9, X, and Y in Compounds 13 and 20 to obtain the Formula I nucleic acid delivery cationic lipid compound with the optimal alkyl hydrophobic tail with a reasonable predictability of success for the purpose of utilizing a hydrophobic tail that will cleave in vivo and deliver a nucleic acid to the optimal location in vivo, see Paras. [0005];[0046]-[0047];[0075].
By applying “routine optimization” and “predictable results” to select the optimal alkyl hydrophobic tail, one of ordinary skill in the art would have been motivated to make these modifications because Ansell provides a finite number of identified, predictable solutions. A person of ordinary skill in the art has good reason to produce a compound structurally similar to Compound 13 or Compound 20 by pursuing the known options within their technical grasp for the benefit of obtaining a structurally similar nucleic acid delivery cationic lipid compound with an alkyl hydrophobic tail in order to utilize a structurally similar hydrophobic tail that will cleave in vivo and deliver a nucleic acid to the optimal location in vivo, see Paras. [0005];[0046]-[0047];[0075]; MPEP 2143, and 2144.09.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Y. Lynnette Kelly-O'Neill whose telephone number is (571)270-3456. The examiner can normally be reached Monday-Thursday, 8 a.m. - 6 p.m., EST, with Flex Time.
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/YO/Examiner, Art Unit 1692
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699