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 .
Detailed Action
This office action is in response to applicant’s communication filed on 8/25/25.
Claims 1-23 are pending in this application. Claim 3 and 13-21 remain withdrawn. New claim 23 is withdrawn as not reading on applicant’s elected species. Thus claims 3, 13-21 and 23 are withdrawn from consideration.
Applicant’s elected species for the cationic lipid of formula (I) was previously found allowable, as shown below.
PNG
media_image1.png
318
402
media_image1.png
Greyscale
As a result, claims 1-2, 4-12 and 22 are being examined in this Office Action.
Objections
Claims 5-7 (also withdrawn claim 14) remain objected to because of the following informalities:
Claims 5-7 are objected because the claimed structures are blurry and hard to discern. The numbering on the hydrocarbon chains are especially blurry. Please include clearer structures for the compounds in the claims.
Appropriate correction is required.
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 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 of this title, 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. 1 03(a) are summarized as follows:
Applicant Claims
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue, and resolving the level of ordinary skill in the pertinent art.
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, 4-5, 8-12 and 22 remain rejected under 35 U.S.C. 103(a) as being unpatentable over Nueberg et al. (US 20100048672, pub date Feb. 25, 2010, in applicant’s IDS filed 2/28/25), in view of Yin (US 20040072769, pub date April 15, 2004), further in view of Cai et al. (RNA, 2004, 10:1957-1966).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Nueberg et al. teaches RNA interference compositions for transfecting oligonucleotides into cells at the mRNA level for mRNA degradation, which includes (see abstract, paragraphs 39, 73-78, and Table 1, first compound):
the oligonucleotide,
a neutral lipid, exemplified by dioleoylphosphatidyl ethanolamine (DOPE),
and a cationic lipid, exemplified by MONI, see below for structure:
PNG
media_image2.png
258
872
media_image2.png
Greyscale
Nueberg et al. also teaches the equivalency of MONI and HEMI, both cationic lipids (Table 1).
The structure of HEMI is shown below (Table 1, second to the last compound):
PNG
media_image3.png
144
876
media_image3.png
Greyscale
HEMI reads on applicant’s formula (I) when A- = Cl-, n = 2, R1 = methyl, R2 = H, R3 = H, R4 = C18H33, R5 = C18H33. HEMI is the same as applicant’s W29.5, which is the last compound in applicant’s claim 5.
Nueberg et al. exemplifies 1:1 and 1:2 molar ratios of cationic lipid (MONI) to neutral lipid (DOPE). (paragraphs 74, 78 and 83)
Furthermore, Nueberg et al. teaches that the MONI/DOPE (or cationic lipid/neutral lipid) combination was used to target the human GAPDH gene in cell lines. Gene silencing was evaluated at the mRNA level. Nueberg et al. showed that the (1:2 mM) liposomal MONI/DOPE formulation was able to achieve efficient GAPDH mRNA knockdown and efficient GAPDH silencing. (paragraph 64, 283)
Additionally the amount of mRNA was measured in Nueberg et al.’s experiments using the combination of neutral lipid and cationic lipid compositions. (paragraphs 272, 278, 283)
Thus it would be reasonable to expect that Nueberg et al.’s combination of neutral lipid and cationic lipid compositions, which was used to evaluate and degrade the mRNA, would read on applicant’s claimed composition of neutral lipid, cationic lipid and mRNA.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Nueberg et al. is deficient in the sense that it does not teach applicant’s 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DiPPE) (claim 22). Instead Nueberg et al. teaches the neutral lipid, dioleoylphosphatidyl ethanolamine (DOPE).
However, Yin teaches the equivalency of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DiPPE) and (DOPE), which are lipids that form liposomes to assist in endosome disruption (paragraph 148).
Nueberg et al. is also deficient in the sense that it does not teach mRNA capping, polyadenylated or modified nucleosides mRNA.
Cai et al. teaches that GAPDH encodes a protein and has capped mRNA’s at the 5’ end and is polyadenylated at its 3’ end. (abstract; page 1959, first column, first paragraph; Figure 2; page 1965, first column, second to fourth paragraphs).
Furthermore, it is reasonable to expect that human GAPDH mRNA, like most eukaryotic mRNA’s, are capped at its 5’ end and polyadenylated at its 3’ end.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Therefore, it would be prima facie obvious to one of ordinary skill in the art at the time of the invention, to substitute Yin’s 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DiPPE) for Nueberg et al.’s (DOPE), since Yin teaches that both of the neutral lipids, DiPPE and DOPE, are equivalent, and form liposomes to assist in endosome disruption.
It would also be prima facie obvious to one of ordinary skill in the art at the time of the invention, to substitute Nueberg et al.’s HEMI for MONI, since Nueberg et al. teaches the equivalency of MONI and HEMI, both cationic lipids.
Thus, at the time of instant invention, a person of ordinary skill in the art would have been motivated to substitute (DOPE) for 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DiPPE), and to substitute MONI for HEMI, with a reasonable expectation of success. Note that an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Furthermore, the recitation of “suitable for transfecting a messenger RNA (mRNA) into a cell” has not been given patentable weight because the recitation occurs in the preamble. A preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
Response to Arguments
Applicant’s arguments have been considered but are not persuasive for the following reasons:
The examiner acknowledges applicant’s argument that “a person of ordinary skill in the art would recognize that siRNA and mRNA are fundamentally different molecules with different structures, properties and delivery challenges. The skilled person would therefore not be motivated to use a composition specifically designed for siRNA delivery for the entirely different purpose of mRNA delivery, nor would they have a reasonable expectation of doing so.” The applicant then goes on to recite publications and Wikipedia to support their assertions.
However, the examiner does not agree with applicant’s arguments.
Agnew et al. (WO 2017218891, pub date 12/21/2017) teaches how both antibody conjugated siRNA and mRNA can be used to target mRNA delivery. Thus teaching the equivalency of using both siRNA and mRNA. (abstract; paragraphs 103-104, 120-125, 146-147)
Also, Farokhzad et al. (WO 2018112470, pub date 6/21/2018; the US equivalent is used here instead US 20200085758, pub date 03/29/2020) teaches how “when siRNA and mRNA are delivered into a cell using a nanoparticle co-loaded with both the siRNA and the mRNA, suppression of gene expression targeted by the siRNA and expression of protein encoded by the mRNA are both increased”. (paragraph 92)
Thus the art shows that siRNA and mRNA composition can be used together or interchangeably.
Furthermore, the recitation of “suitable for transfecting a messenger RNA (mRNA) into a cell” has not been given patentable weight because the recitation occurs in the preamble. A preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
The examiner asserts that applicant’s claims are drawn to a composition and not to a process. For applicant’s composition claims, the property of the composition is inherent to the structure of the compounds in the composition. Applicant’s process claims (including the process for transfecting a mRNA into a cell) were restricted out in the restriction filed 12/19/24.
Since Nueberg et al.’s composition contains a combination of neutral lipid and cationic lipid, interacting with mRNA, in which the mRNA levels were measured, the examiner asserts that Nueberg et al.’s composition reads on applicant's claims. Thus it would be reasonable to expect that Nueberg et al.’s combination of neutral lipid and cationic lipid compositions, which was used to evaluate and degrade the mRNA, would read on applicant’s claimed composition of neutral lipid, cationic lipid and mRNA.
Conclusion
No claim is 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 extension fee 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 Jennifer Cho Sawyer whose telephone number is (571) 270 1690. The examiner can normally be reached on Monday-Friday 9 AM - 6 PM PST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-274-1690.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Jennifer Cho Sawyer
Patent Examiner
Art Unit: 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691