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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/20/2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim interpretation
The term “about” is given its broadest possible interpretation in view of the specification and can be interpreted to encompass values
±
20
%
of the claimed value or range.
Preferable embodiments are not being given patentable weight as they are not required by the claim.
Claim 2 is directed to intended use of the composition recited in claim 1. However, the claim does not further limit the structure or composition of the claimed composition of claim 1.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
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.
Claims 8-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Claims 8-10 recite the limitation "said" in the context of ionizable lipids, sterol, PEG-lipids and phospholipids. There is insufficient antecedent basis for this limitation in the claim. It is unclear as to which lipids these claims are directed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Besin et al (WO2017099823A1; published Jun 15, 2017; hereinafter “Besin;” See PTO-892).
Regarding claims 1-2: Besin disclosed “In some embodiments, the molar lipid ratio is 50/10/35/4.5/0.5 (mol% cationic lipid/non-cationic lipid/structural lipid/PEG lipid).“ (See Besin, p. 90, lines 15-20). Besin disclosed that non-cationic lipids can be phospholipid and structural lipid can be a sterol. (See Besin, p. 90, lines 23-27). Further claim 33 of Besin taught that the lipid nanoparticle can be used for delivering nucleic acid such as mRNA. As such, Besin disclosed every aspect of the invention.
Claims 8-10 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Aknic et al (WO2010088537A2; published Aug 5, 2010; hereinafter “Aknic;” See PTO-892).
Regarding claims 8 -10: Aknic disclosed “A lipid formulation comprising 45-65% of cationic lipid of formula A, 5-10% of the neutral lipid, 25-40% of the sterol, and 0.5-5% of the PEG or PEG-modified lipid” (See Aknic claim 1). Aknic further taught that the neutral lipid could be DPPC or DOPC which are phospholipids. (See Aknic claim 2). The ranges disclosed by Aknic anticipate the claimed ranges for ionizable lipid, neutral lipid or PEG-lipid in claims 8-10. As such, the subject matter of the claims are anticipated by the disclosure in Aknic.
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 3-4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (US8158601B2; published as Apr 17, 2012; hereinafter “Chen;” See PTO-892) in view of Santos et al (Biochim Biophys Acta. 2007 Jun; hereinafter “Santos;” See PTO-892).
Regarding claims 3, 4 and 6: Chen disclosed a lipid nanoparticle (LNP) comprising: 40-65% of cationic lipid, 5-10% of a neutral lipid, 25-40% of a sterol, and 0.5-10% of a PEG or PEG-modified lipid. (See Chen claim 3). Further claim 4 of Chen taught that the neutral lipid can be DSPC or DPPC, among other, which are phospholipids. Santos taught that “0.5 mol% of 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE) modified with PEG having a mean molecular weight of 2000 (DSPE-PEG(2000)) substantially increased plasma circulation longevity of liposomes” (See Santos Abstract). It is noted that the liposomes used in Santos are made of DSPC (phospholipid) and are cholesterol free. However, one of ordinary skill in the art would have been motivated to use between 0.5%-2% PEG2K-DSPE in view of the advantages stated in Santos, such as improvement of longevity of the liposomes. As such it would be obvious to combine the teachings of Koker and Santos to arrive at the claimed liposome composition. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted)
Claims 5, 7 and 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (US8158601B2; published as Apr 17, 2012; hereinafter “Chen;” See PTO-892) in view of Santos et al (Biochim Biophys Acta. 2007 Jun; hereinafter “Santos;” See PTO-892) and further in view of Narayanan et al (WO2018175783A1; published Sep 27, 2018; hereinafter “Narayanan;” See PTO-892) .
Regarding claim 5: As indicated above, Chen taught use of lipid nanoparticle comprising specific quantities of cationic, phospholipids, sterols and PEG-lipids. However, Chen did not teach the claimed ionizable lipids as required by the claim. However, Narayanan taught use of ionizable lipids comprising Dlin-MC3-DMA for making liposomes for use as mRNA-vaccine (See Narayanan p. 5, lines 20-25). As such it would have been obvious for a person of ordinary skill in the art to use the ionizable lipids for making mRNA vaccine. One of ordinary skill would recognize this as substituting one ionizable lipid for another useful for the same purpose ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12), i.e. making mRNA vaccines.
Regarding claim 7: Chen taught that the sterol can be cholesterol. (See Chen col.4, lines 23-27)
Regarding claims 11-13: Narayanan taught a liposome comprising an RNA encoding having an open reading frame encoding at least one Streptococcal antigenic polypeptide. (See Narayanan claim 48).
Regarding claim 14: Chen taught liposomes and a pharmaceutically acceptable carrier (See Chen col. 77, lines 50-60).
Regarding claim 15: Narayanan taught that the liposomes can be used for treatment of infectious diseases (See Narayanan p. 61, lines 1-10).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17-35 of copending Application No. 18/008,877 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons stated below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1-2: Claim 1 of reference application is directed to an mRNA comprising lipid nanoparticle comprising the following elements and thus anticipates the claim.
Component
Instant application
Reference application
Ionizable lipid
about 45 - 65 mol%
about 55 mol% to about 60 mol%
Phospholipid
about 4 - 15 mol%
about 5 mol% to about 10 mol%
PEG-lipid
less than about 1 mol%
0.5 mol% to about 0.9 mol%
Regarding claims 3-4: The claims of the reference application taught the indicated concentrations of ionizable, phospholipid and PEG-lipid contents. It is noted that none of the claims of the reference application taught a C18-PEG2K as required by the claim. However, optimizing the length of the acyl-chain of PEG-lipid is routine in the art. For example, Wan taught that “PEG-lipids with short acyl chains have been developed that quickly dissociate from the LNPs following injection, allowing them to interact with target cells. The acyl chain length determines the rate at which the PEG-lipids dissociate from the nanoparticles. For example, PEG-lipids with C14 acyl chains dissociate from LNPs with half times of around 1 h, versus PEG-lipids with C20 acyl chains with half times of 24 h or longer” (See Wan, p. 77, col. 1, para 2). As such it would have been obvious for a person of ordinary skill in the art to arrive at the C18PEG-2K or the claimed C18 PEG2K lipids as claimed in claim 4 through routine optimization. Moreover the person would have been motivated to arrive at the claimed composition due to the benefits of the longer acyl-chain of PEG-lipids as taught by Wan.
Regarding claim 5: Claim 24 of the reference application recites the claimed ionizable lipids and is thus anticipated.
Regarding claim 6: Claim 26 of the reference application recites the claimed phospholipids and is thus anticipated.
Regarding claim 7: Claims 28-29 of the reference application recites the claimed sterol and is thus anticipated.
Regarding claims 8-10: Claim 31 of the reference application recites the following elements and thus anticipates the claim.
Component
Instant application
Reference application
Claim 8
Claim 9
Claim 10
Ionizable lipid
above 60 mol%
about 64 mol%
about 64 mol%
about 65 mol%
Phospholipid
about 8 mol%
about 9.5 mol%
PEG-lipid
about 0.5 - 0.9 mol%
about 0.5 mol%
about 0.5 mol%
Regarding claim 11-12: Claim 32 of the reference application recites one or more mRNA molecules selected from immunomodulatory polypeptide-encoding mRNA or antigen-encoding mRNA and is thus anticipated.
Regarding claim 13: Claim 33 of the reference application recites mRNA molecules encoding for CD40L, mRNA molecules encoding for CD70, and mRNA molecules encoding for caTLR4 and is thus anticipated.
Regarding claim 14: Claim 34 of the reference application recites mRNA liposome and an acceptable pharmaceutical carrier and is thus anticipated.
Regarding claim 15: Claim 34 of the reference application recites treatment of infectious disease or cancer.
Conclusion
No claim is free of art.
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M. Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAGAMYA NMN VIJAYARAGHAVAN/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633