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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/18/2026 has been entered.
Status of the Claims
Claims 23, 27, and 32-42 are pending in this application. Claims 1-22, 24-26, and 28-31 have been cancelled by applicant. Claims 23, 27, 32, and 34-42 are under examination herein. Claim 33 is withdrawn from consideration.
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.
Claims 23, 27, 32, and 34-42 are rejected under 35 U.S.C. 103 as being unpatentable over Guild et al. (US 10,507,249 B2 – previously cited) (“Guild”); in view of Le Corre et al. (Eur. J. Org. Chem. 2014, 8041–8048 – cited in IDS – previously cited) (“Le Corre”).
Regarding claims 23, 27, and 34-35, Guild discloses lipid nanoparticle compositions and methods of mRNA delivery (title and abstract). Guild teaches one reason that mRNA-based gene therapy has not been used more in the past is that mRNA is far less stable than DNA, especially when it reaches the cytoplasm of a cell and is exposed to degrading enzymes; certain delivery vehicles may also help protect the transfected mRNA (col. 2, last para.); Guild discloses compositions and methods for intracellular delivery of mRNA in a liposomal transfer vehicle (col. 3, lines 24-26). Guild discloses their mRNA is formulated in a liposomal transfer vehicle may comprise one or more non-cationic lipids, PEG-modified lipids, and may further comprise cholesterol (reading on a sterol – claim 27) (col. 4, lines 15-17). Guild discloses their compositions comprise a transfer vehicle, such as pharmaceutically acceptable carriers, diluents, excipients, etc. (reading on claims 23, 27, and 32) (col. 9, lines 5-10). Guild further discloses the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell (col. 14, lines 13-16). Guild teaches liposomes (e.g., liposomal lipid nanoparticles) are generally useful in a variety of applications in research, industry, and medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo (col. 14, lines 31-35), and that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (col. 14, lines 40-43).
Regarding claim 32, Guild teaches their pharmaceutical compositions comprise a transfer vehicle, such as pharmaceutically acceptable carriers (col. 9, lines 5-10).
Regarding claims 36-42, Guild discloses delivery of mRNA (reading on RNA, polynucleotides, and agent).
While Guild does not specifically teach the instantly elected non-cationic phosphate lipid with a dimethylamine polar head, the teachings of Le Corre are relied upon for these disclosures.
Le Corre discloses compound 7 below, which is the same as the instantly elected species (Scheme 1(B), page 8043). Le Corre discloses how their liposome formulations were prepared with the cationic lipid 11 derived from the elected compound in the instant invention (page 8047, col. 2, para. 2).
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, wherein the Olelyl group is defined as:
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Therefore, regarding instant claims 23, 27, and 34-35, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a composition comprising the instant compounds and mRNA; or a nanoparticle comprising the instant alkyl phosphate lipid (amphiphilic ionizable compound 7) and mRNA, for intracellular delivery as taught by Guild in view of Le Corre. One of ordinary skill would have been motivated to do so because Guild teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains, such as Le Corre’s compound 7, and that liposomes are useful in medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo; further because Le Corre’s discloses their ionizable amphiphilic compound 7 (a precursor of a cationic lipid 11, which showed good transfection efficacies (see Figure 3 of Le Corre)). One of ordinary skill would have had a reasonable expectation of success in doing so in view of Guild’s teachings of lipid nanoparticle compositions comprising one or more non-cationic lipids, PEG-modified lipids and cholesterol, Guild’s methods of mRNA delivery, and Guild’s teachings that the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell; further in view of Le Corre’s teachings of compound 7 and methods of formulating liposomes. A person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Claim Rejections - 35 USC § 112(b)
In view of claim amendments, 35 USC § 112(b) rejections have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 05/18/2026 have been fully considered but they are not persuasive. The rejection has been modified slightly for the purposes of clarity and conciseness; however, Applicant’s arguments were not persuasive.
Applicant argues that Guild’s reference to non-cationic lipids refers to helper lipids listed (see page 7 of the arguments), and that one of ordinary skill would recognize that the presently claimed ionizable lipid represents a distinct class from Guild’s broad reference to non-cationic lipids. Applicant argues Le Corre and Guild provide no reason that would lead one of ordinary skill to stop at intermediate 7 and test it for its ability as an ionizable lipid. Applicant argues that the mere fact that a compound is amphiphilic and or non-cationic is not enough to show that the intermediate compound has a specific utility that would encourage one of ordinary skill to consider using it in the claimed composition. Applicant asserts Examiner used hindsight reasoning to arrive at the rejection of record.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Guild discloses lipid nanoparticle compositions and methods of mRNA delivery (title and abstract). Guild discloses their mRNA is formulated in a liposomal transfer vehicle may comprise one or more non-cationic lipids, PEG-modified lipids, and may further comprise cholesterol (reading on a sterol – claim 27) (col. 4, lines 15-17). Guild teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains (col. 14, lines 40-43).
Le Corre discloses the amphiphilic compound 7 below.
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to prepare a composition comprising the instant compounds and mRNA; or a nanoparticle comprising alkyl phosphate lipid 7 (amphiphilic compound) and mRNA, for intracellular delivery as taught by Guild in view of Le Corre. One of ordinary skill would have been motivated to do so because Guild’s teaches that liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains, and that liposomes are useful in medicine, particularly for their use as transfer vehicles of diagnostic or therapeutic compounds in vivo; further because Le Corre’s discloses their ionizable amphiphilic compound 7 as a precursor of a cationic lipid for use in a liposome formulation with good transfection efficacies. One of ordinary skill would have had a reasonable expectation of success in doing so in view of Guild’s teachings of lipid nanoparticle compositions comprising one or more non-cationic lipids, PEG-modified lipids and cholesterol; Guild’s methods of mRNA delivery; and Guild’s teachings that the properties of the transfer vehicle (e.g., size, charge and/or pH) may be optimized to effectively deliver transfer vehicle to the target cell, reduce immune clearance and/or promote retention in that target cell; further in view of Le Corre’s teachings of compound 7 and methods of formulating liposomes. A person with ordinary skill has good reason to pursue known options within his or her technical grasp.
In response to Applicant’s argument that Guild discloses their non-cationic lipids listed in page 7 of the response filed 05/18/2026, Guild specifically states their list is non-limiting (see col. 18, lines 40-41) – thus, one of ordinary skill in the art would be able to see that Le Corre’s compound 7 is also a non-cationic lipid, and thus be motivated to use it in Guild’s composition. One would have been further motivated to do this because compound 7 is an ionizable non-cationic lipid, disclosed as a precursor of cationic lipid 11, which showed high transfection rates in their studies. As such, one would expect that ionizable compound 7 would afford good transfection rates when used in Guild’s composition. Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
In response to Applicant’s argument that the mere fact that Le Corre’s compound 7 is amphiphilic and or non-cationic is not enough to show that the intermediate compound has a specific utility that would encourage one of ordinary skill to consider using it in the claimed composition; In view of the arguments outlined above, Applicant needs to demonstrate a special ability of the claimed composition comprising ionizable compound 7 in achieving delivery into cells not observed with Le Corre’s liposome formulation comprising the alkylated derivative of compound 7 (compound 11 in Le Corre). A comparison of the efficacy of transfection of the instant compositions compared to Le Corre’s composition comprising a cationic compound 11 would suffice to overcome obviousness rejections of record.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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