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 .
Priority
Acknowledgement is made of the Applicant’s claim of domestic priority to provisional US application 63/508,782 filed 16 June 2023.
Examiner's Note
Applicant's amendments and arguments filed 10 August 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant's response, filed 10 August 2026, it is noted that claims 81-82 have been newly added. Support can be found in the claims as originally filed.
Status of the Claims
Claims 1-7, 10-11, 13, 15-17, 20, 23-25, 28-29, 31-33, 36, 39, 43, 45, 47-49, 51, 57, 59-61, 76, and 81-82 are pending.
Claims 1-7, 10-11, 13, 15-17, 20, 23-25, 28-29, 31-33, 36, 39, 43, 45, 47-49, 51, 57, 59-61, 76, and 81-82 are rejected.
Claim Rejections - 35 USC § 112
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.
Claim 82 is 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. Claim 82 recites variable R1d two times with two separate definitions, thus rendering it indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6-7, 10-11, 13, 15-17, 20, 23-25, 28-29, 31-33, 36, 39, 43, 45, 47-49, 51, 57, 59-61, 76, and 81-82 are rejected under 35 U.S.C. 103 as being unpatentable over Bartolozzi et al. (WO 2023/091490).
Bartolozzi teaches the following compound 2241 (pg 39) wherein the compound corresponds to Formula I when G1 is N, L1 and L2 are C7 alkylene, R1 and R2 are -C(=O)NHC14H29, and R3 is -C(=O)R3a wherein R3a is C2 alkyl and a heterocycle. These compounds can be formed into lipid nanoparticles and used in the delivery of therapeutic cargos (abstract).
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Compound 2242 (below) demonstrates how the nitrogen can be substituted with two different alkyl groups (pg 39). The X group can be -C(O)N(R7)- wherein R7 is hydrogen or alkyl (pg 4).
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In a more general formula, Bartolozzi teaches that the X group (below) can be -NHCO- or -CONH- and that each A and B can be C1-C16 branched or unbranched alkyl group (pg 2). In yet an another alternative embodiment, the X group is defined as -N(R7)C(O)- wherein R7 is hydrogen or alkyl (pg 4).
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Bartolozzi also teaches variation in the “head group” nitrogen (below) wherein R20 and R30 to be C1-C5 alkyl (pg 2). The Z group can be oxygen (pg 2).
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The lipid nanoparticle composition can comprise an mRNA and a cholesterol (active agent) (pgs 161-162) and can be used to inject intravenously in mice (pgs 163-164).
Bartolozzi does not teach the structure of Formula I wherein the amide nitrogen is alkylated, as required in instant claim 1.
It would have been prima facie obvious to modify the 2241 compound wherein the X group amide is inverted to be -NHCO-. In addition, the B group can be any C1-16 alkyl, so it would have been obvious to replace the branched chain alkyl with a C10 alkyl chain. The resulting structure as shown below renders obvious instant claims 1-2, 16-17, 20, 32-33, 36, 45 (which comprises an optional limitation not required to be present), 48-49, and 51. Modifying the alkyl chaing length from the center nitrogen is obvious, rendering obvious instant claim 57. When combined in a lipid nanoparticle with RNA and a therapeutic agent and dosed to a mouse, as taught by Bartolozzi, the composition further renders obvious instant claims 60-61 and 76.
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Regarding claim 6 and its dependents, it would have been prima facie obvious to modify the 2242 structure of Bartolozzi, wherein the nitrogen is substituted by two alkyl groups, so that both alkyl groups are branched or unbranched C4-C16, since any alkyl group is permitted in the prior art. Moreover, it is obvious to modify the “head group” to any chain length alkyl group since the generic structure permits R20 and R30 to be C1-C5 alkyl. The following structure, or wherein the alkyl groups are C16, is obvious from Bartolozzi and renders obvious instant claims 1, 6, 10-11, 13, 15, 23-25, 28-29, 31, 39, 43, 59-61, 76, and 81-82. By modifying the Z group to be oxygen, instant claim 47 is rendered obvious.
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Claims 1-7, 10-11, 13, 15-17, 20, 23-25, 28-29, 31-33, 36, 39, 43, 45, 47-49, 51, 57, 59-61, 76, and 81-82 are rejected under 35 U.S.C. 103 as being unpatentable over Maier et al. (US 2013/0195920).
Maier teaches cationic lipid moieties incorporated into a particle further comprising a nucleic acid and a sterol (abstract). Maier teaches the following compound (pg 175) wherein the compound corresponds to Formula I when G1 is CH, L1 and L2 are C7 alkylene, R1 and R2 are -C(=O)NHC9H17, and R3 is -OC(=O)-R3a wherein R3a is C3 alkyl substituted with N(CH3)2.
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Maier also teaches the following compound wherein X can be NH (pg 180).
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It is noted that Maier teaches many alternative chains for the above compound including the following chain to replace the lefthand portion comprising an ester [0133].
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In the broadest formula (I), Maier teaches that the Q group can comprise -O-, -C(O)O-, -OC(O)-, or -N(R5)C(O)- wherein R5 can be hydrogen or alkyl [0007, 0017]. The R group is an alkyl group [0013]. In addition, the M1 and M2 groups can be -C(O)O-, -OC(O)-, or -N(R5)C(O)-, or -C(O)N(R5)- and Z1 and Z2 can be C8-C14 alkyl [0021, 0025].
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That being said, the following compounds would have been obvious based on the broad teachings of Maier. Said compound renders obvious instant claims 1, 3-5, 16-17, 20, 32-33, 36, 43, 45, 48-49, 51, and 81.
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By following the guidance of Meier and inverting and/or substituting alkyl groups on the tail nitrogens and/or modifying the Q group to be an ether and/or modifying the substitutions on the head group as per the prior art, instant claims 6-7, 10-11, 13, 15, 23-25, 28-29, 31, 39, 47, 57, 59, and 81-82 are rendered obvious.
Regarding instant claims 60-61 and 76, Meier teaches formulating the lipids with a therapeutic agent (such as a nucleic acid) as a nanoparticle and using them in a method of modulating expression of a target gene in a cell [0182, 0187].
Response to Arguments
Applicant's arguments filed 10 August 2026 have been fully considered but they are not persuasive. The Applicant argues, on pages 16-21 that there is no motivation in Bartolozzi to make the structural modifications needed to produce a compound of Claim 1. The Applicant further argues that the fact a claimed species or subgenus is merely encompassed by prior art is not sufficient to establish a prima facie case of obviousness and that some reason must be identified that would have led a chemist to modify the known compound in a particular manner. Specifically, the Applicant argues there was no motivation to replace the C14 alkyl group with a C10 alkyl group because it would have led to a dramatic reduction in selectivity.
In response, Bartolozzi teaches a very broad scope of compounds that can be interpreted, as described in the above rejection, as reading on the instantly claimed compounds. That being said, it is true that the prior art does not specifically motivate modifications to achieve the claimed compounds. That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Consistent with this reasoning, it would have been obvious to have selected various combinations of Markush variables from within Bartolozzi, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Regarding the Applicant’s assertion that the skilled artisan would not have been motivated to modify compound 2241 in the ways described in the rejection above, it is noted that the Applicant is erroneously pointing to narrow embodiments expressly disclosed within the prior art reference as representing the sum total of information conveyed by each. Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments (see MPEP § 2123). The selectivity data shows preferred species but does not show that the claimed species would be inoperable. In response to the Applicant's argument that the references fail to show certain features of applicant’s invention, it is reminded that to properly teach away, the prior art reference must criticize, discredit, or otherwise discourage the solution sought. Merely teaching alternatives does not do this (see MPEP 2145 (X)(D)). As such, in lieu of evidence of an unexpected result, the proposed modifications described in the above rejection would have been obvious based on the broad Markush structures of Bartolozzi.
The Applicant argues, on pages 22-25 of their remarks, that Maier does not teach the specific motivation to make the structural modifications needed to produce a compound of Claim 1 and that there is no motivation to modify the compound of page 175 because doing so would not have been expected to improve the stability of the resulting compound.
In response, as stated above, the teachings of KSR are actually an endorsement and expansion of the flexible and expansive approach to obviousness, which clearly invites continued reliance on such broad and flexible analyses concerning the utility of selecting alternative embodiments of components providing art-recognized utility, with no substantial change in the overall utility of a composition so formulated. See KSR International Co. v. Teleflex, Inc., 82 USPQ2d 1385, 1395-96 (U.S.2007) (“the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”; “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious”; “a court must ask whether the improvement is more than the predictable use of prior art elements according to their established functions” exemplified by the holdings of cases such as Merck v. Biocraft.
Moreover, In response to the Applicant's argument that the references fail to show certain features of applicant’s invention, it is reminded that to properly teach away, the prior art reference must criticize, discredit, or otherwise discourage the solution sought. Merely teaching alternatives does not do this (see MPEP 2145 (X)(D)). As such, in lieu of evidence of an unexpected result, the proposed modifications described in the above rejection would have been obvious based on the broad Markush structures of Maier.
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 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 ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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