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 .
Applicants' arguments, filed 07/23/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
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.
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.
Previous
Claim(s) 78-96, 99-101 is/are rejected under 35 U.S.C. 103 as being unpatentable over Song et al., (CN114044741, cited in IDS).
Song et al. teaches compounds of the following formula:
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(Abstract). The claimed compound YK-108
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is a compound of the formula of Song et al. where G3 is C2 alkylene; G2 is C6 alkylene; G1 is C3 alkylene; L1 is C11 linear alkyl and L2 is C12-25 branched alkyl or
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(see p. 6 paras. [0007]-[0013]). The prior art teaches a specific embodiment:
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474
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(p. 4, para. [0025]), which is close enough to the claimed compound to reasonably expect the same properties.
The prior art teaches:
The present disclosure is based on at least the following discovery: structure of cationic lipid compound and intracellular transfection efficiency, toxicity generated by the cell and no obvious corresponding relation between high expression and continuous expression in the animal body. small structure difference of the compound, the transfection efficiency and/or toxicity of the cell, high expression in the cell difference is very large, such as the compound YK-009 and YK-010, cell transfection efficiency difference is nearly 60 times, the toxicity difference of the transfection cell is more than 25 %; the expression of the compound YK-003 and YK-010 in the mouse body and the continuous expression difference can reach 50 times. (see 4th page, 3rd paragraph).
The compounds of Song et al., including the claimed YK 108, are “capable of simultaneously having high transfection efficiency and low toxicity to the cell” (Id. 4th paragraph)
The compounds of Song et al. are taught to be formulated in compositions requiring a carrier comprising the cationic lipids or pharmaceutically acceptable salts thereof (Abstract: clm. 78), wherein the molar ratio of cationic lipid to carrier is 30% to 70% (5th page, line 5 of translation; clm. 79). The carrier can further comprise a “neutral lipid” (Id. line 8; clm. 80), e.g., “phosphatidylcholine” (Id. lines 8-22; clm. 82), “DLPC” (Id.; clm. 83), wherein the molar ratio of cationic lipid to neutral lipid is “1:1 to 10:1” (Id. lines 6-7;clm. 81); a “structured lipid” (6th page, line 7; clm. 84), e.g., “cholesterol” (Id. line 9; clm. 86), wherein the molar ratio of cationic lipid to structured lipid is “1:1 to 5:1” (Id. lines 7-8; clm. 85); a “polymer-conjugated lipid” (6th page, 5th paragraph; clm. 87), e.g., “PEG” modified compounds (Id. 6th paragraph; clm. 89) or “DSPE-PEG2000” (Id. clm. 90), wherein the mol ratio amount of polymer-conjugated lipid is present from “0.5% to 5%” (Id. 5th paragraph; clm. 88); “other ionizable lipid compound” (Id. paragraph 10; clm. 93); “therapeutic agents” (Id. paragraph 11;clm. 94), wherein the mass ratio of carrier to agent is “15:1 to 25:1, preferably 16:1” (clm. 95; Id), e.g., nucleic acids molecules (clm. 96; Id at paragraph 12), such as DNA (clm. 99, 101; Id. paragraph 15) and RNA, e.g. “small interfering RNA (siRNA)” (clm. 100; 7th page, 1st and 2nd paragraphs).
In regard to claim 91, the prior art teaches an embodiment where the carrier comprises “the cationic lipid, the neutral lipid, the structural lipid, and the mol ratio of the polymer conjugated lipid is (25-65): (5-25): (25-45); (0.5-5), preferably 50:10:38:5:1.5” (6th page paragraph 8).
In regard to claim 92, the lipid particles have an average particle diameter of “10nm to 205 nm” (6th page paragraph 8) and multi-dispersion coefficient not more than 50% (Id.).
The prior art is not anticipatory insofar as it does not teach the exact formula of YK108;however, it would have been obvious to a person having ordinary skill in the art to make YK108 given that its core structure and option for variables in the structure are taught by Song et al. The artisan would have been further motivated to modify the core structure since small changes can have a big impact on efficacy. Song et al. teaches “small structure difference of the compound, the transfection efficiency and/or toxicity of the cell, high expression in the cell difference is large, such as the compound YK-009 and YK-010, cell transfection efficiency difference is nearly 60 times, the toxicity of the transfection cell is more than 25%; the expression of the compound YK-003 and YK-010 in the mouse body and the continuous expression difference can reach 50 times” (p. p. 11, 1st paragraph).
New
2) Claim(s) 78-96, 99-101 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benenato et al., (WO2018170306).
Benenato et al. teaches compounds of the following formula:
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(p. 22, para. [0028]). The claimed compound YK-108
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is a compound of the formula of Benenato et al. where R’ is C1-18 alkyl; R” is C3-15 alkyl; n is 2; m is 6; R5, R6 and R2 are H; R3 is C1-14 alkyl (see p. 2-11 paras. [0007]-[0016]). The prior art teaches a specific embodiment:
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(p. 59), which is close enough to the claimed compound to reasonably expect the same properties.
The prior art teaches that these compounds are for intracellular delivery of therapeutic agents. “Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/ or prophylactics to mammalian cells or organs, for example, regulate polypeptide, protein, or gene expression” (Abstract; clms. 87, 89).
The compositions may also include “pharmaceutically acceptable salts” (p. 112, [00254]; clm. 78).
“A phospholipid including in the lipid component of a nanoparticle composition may facilitate transfection and/or increase transfection efficiency, for example, by interacting and/or fusing with a cellular or intracellular membrane. Transfection may allow for the translation of the mRNA within the cell” (p. 165-166, para. [00445]).
Data therein showed “that repeat dosing of mRNA containing lipid nanoparticles of the disclosure results in maintenance of circulating LNP levels without any signs of toxicity” (p. 435, para. [00540])
The compounds of Benenato et al. are taught to be formulated in “lipid nanoparticle compositions” comprising “one or more ionizable amino lipids, phospholipids including polyunsaturated lipids, PEG lipids, structural lipids, and/or therapeutic and/or prophylactics in specific fractions” (p. 1, para. [0003]; clm. 84, 93, 94). The carrier can further comprise a neutral lipid, e.g., “phosphatidylcholine” (p. 118, [00278]; clm. 80, 82) and “DLPC” (p. 117, [00278]; clm. 83).
“Lipids are designed to yield desired molar ratios (see, for example, Table 23) and diluted with water and ethanol to a final lipid concentration of between about 5.5 mM and about 25 mM” (p. 373, [00444]). Accordingly, it would have been obvious to vary the molar ratios of lipids, as per claims 79, 81, 85, 88, 95. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
Suitable components include “Structural lipids”, e.g., “cholesterol” (p. 116, [00276]; clm. 84, 86 (Id. lines 7-8; clm. 85); or “PEG-DSPE” (polymer-conjugated) (Id. [00275] clm. 87, 89, 90), nucleic acids molecules (clm. 96; p. 120, [00284]), such as DNA (clm. 99, 101) and RNA, e.g. small interfering RNA (siRNA) (clm. 100).
In regard to claim 91, the prior art teaches an embodiment where the carrier comprises a compound of formula (I):DSPC:cholesterol:PEG-DMG of “50:10:38:5:1.5” (p. 376 [00456]).
In regard to claim 92, “a nanoparticle composition may be a liposome having a lipid bilayer with a diameter of 500 nm or less” (p. 110, [00246]), with a “polydispersity index of” . . . “from about 0.10 to about 0.20” (p. 155, [00411]).
The prior art is not anticipatory insofar as it does not teach the exact formula of YK108;however, it would have been obvious to a person having ordinary skill in the art to make YK108 given that its core structure and option for variables in the structure are taught by Benenato et al. The artisan would have been further motivated to modify the core structure since small changes can have a big impact on efficacy. Benenato et al. teaches “The elements of a nanoparticle compositions may be selected based on a particular application or target, and/or based on the efficacy, toxicity, expense, ease of use, availability, or other feature of one or more elements. Similarly, the particular formulation of a nanoparticle composition may be selected for a particular application or target according to, for example, the efficacy and toxicity of particular combinations of elements” (p. p. 152, [00402]).
Response to Arguments
Applicant argues that CN11440443741 in not prior art insofar as it was published within the 1 year grace period of the filing of the instant application.
However, according to MPEP 2155 applicants are instructed to “submit an appropriate affidavit to declaration to disqualify a disclosure as prior art by establishing that the disclosure was made by the inventor or a joint inventor, or the subject matter disclosed was obtained or indirectly from the inventor or joint inventor” (37 C.F.R 1.130).
The rejection will be maintained in absence of said affidavit or declaration.
Conclusion
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/ Primary Examiner, Art Unit 1612
Prosecution Insights