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 .
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 3 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.
"Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table 'is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.' Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)" (MPEP 2173.05(s)).
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.
Claims 1, 2, 4, 7, 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kotin (WO2019/051289).
Regarding Claim 1, Kotin discloses a method for the delivery of prenatal therapeutics, enzyme replacement therapy, or gene therapy to a fetus in need thereof (lipid nanoparticle formulations that comprise an ionizable lipid, Abstract; lipid nanoparticle LNP formulations of viral, capsid-free DNA vectors and their use for the delivery of exogenous DNA sequences to a target cell, tissue, organ or organism, Para. [0003]; a composition comprising a first lipid nanoparticle and an additional compound, Para. [0026]; the additional compound is a therapeutic agent, Para. [0029]; term "subject" as used herein refers to a human or animal, to whom treatment, including prophylactic treatment, with the ceDNA vector according to the present invention, is provided the subject can be a neonate or an unborn subject, e.g., the subject is in utero, Para. [0089]; The compositions provided herein can be used to deliver a transgene the transgene encodes one or more peptides, polypeptides, or proteins, which are useful for the treatment, amelioration of disease states in a mammalian subject, Para. [00231]), comprising introducing ionizable lipid nanoparticles (LNPs) nanoparticles comprising a therapeutic mRNA composition (novel lipid formulations comprising an ionizable lipid and a capsid free, non-viral vector ceDNA, Para. [0005]; a nucleic acid of interest. is incorporated into and may be delivered and expressed by a ceDNA vector nucleic acids of interest include nucleic acids that are transcribed into therapeutic RNA, Para. [0063]; A sequence encoding a polyadenylation sequence can be included in the ceDNA vector to stabilize the mRNA expressed from the ceDNA vector, Para. [00309]) into the circulation of the fetus in need of treatment (administration is by any of the routes normally used for introducing a molecule into ultimate contact with blood Exemplary modes of administration includes. in utero, Para. [00234]) wherein the ionizable LNPs deliver the therapeutic mRNA composition (a lipid nanoparticle of the invention includes a lipid formulation that can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest the lipid nanoparticle comprises capsid-free, non- viral DNA vector and an ionizable lipid, Para. [00101]).
Regarding Claim 2, Kotin discloses the method of claim 1, wherein the ionizable LNPs comprise: one or more ionizable polyamine-lipids; cholesterol; 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); and a pegylated lipid (PEG-lipid) (lipid nanoparticle compositions for such delivery are composed of synthetic ionizable lipids, phospholipids (especially compounds having a phosphatidylcholine group), cholesterol, and a polyethylene glycol (PEG) lipid, Para. [0057]; the non-cationic lipid is a phospholipid the non-cationic lipid is DOPE, Para. [00161]).
Regarding Claim 4, Kotin discloses the method of claim 2, wherein the PEG-Lipid is 1,2-dimyristoyl-snglycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (C14-PEG2000) (The PEG-lipid can be... 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-fmethoxy/polyethylene glycol)-2000], Para. [00174]).
With regards to claim 7, the method is directed to a method of treatment, therefore the limitations with regards to the method of making the LNPs are viewed as product by process limitations, and not limiting where the end product of the prior art is the same as is instantly claimed, regardless the efficiency.
With regards to claim 8, the pKa is a property of the LNP, therefore where the LNP is anticipated, the properties of the LNPs are likewise satisfied, whether recognized or not.
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.
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 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Kotin (WO 2019/051289) in view of Billingsley et al (Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering, Nano Letters, 2020, Vol 20, Iss 3, pp 1578-1589).
Regarding Claim 3, Kotin discloses the method of claim 2.
Kotin fails to explicitly disclose wherein the one or more ionizable polyamine-lipids is selected from the group consisting of formulations: A-1 through A-5, B-1 through B-5, and C-1 through C-4 as described in Figs. 2A and 2C.
Billingsley is in the field of ionizable lipid nanoparticle-mediated mRNA delivery in humans (Title) and teaches he one or more ionizable polyamine-lipids is selected from the group consisting of formulations: A-1 through A-5, B-1 through B-5, and C-1 through C-4 as described in Figs. 2A and 2C (compounds 2, 5, and 8, Fig. 2B).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of Kotin by a lipid as taught by Billingsley for the purpose of achieving enhanced mRNA delivery (Billingsley, Abstract).
Regarding Claim 5, Kotin discloses the method of claim 4.
Kotin fails to explicitly disclose wherein the one or more ionizable polyamine lipids, cholesterol, DOPE, and C14-PEG2000 are at respective molar ratios of about 35:46.5:16:2.5.
Billingsley is in the field of ionizable lipid nanoparticle-mediated mRNA delivery in humans (Title) and teaches he one or more ionizable polyamine lipids, cholesterol, DOPE, and C14-PEG2000 are at respective molar ratios of about 35:46.5:16:2.5 (optimized LNP formulations for mRNA delivery, which generally utilized (i) DOPE as the phospholipid component, (ii) a decreased molar percentage of ionizable lipid, and (iii) increased concentrations of cholesterol and lipid-anchored PEG. Given that alterations in the molar ratio of excipients impact the physicochemical properties and ultimately potent delivery of LNPs, the ratio of the components was held constant throughout these experiments, Pg. 5, second full paragraph from bottom; To prepare the ethanol phase, ionizable lipid, 1,2-distearoyl-sn-glycero-3-phospheethanolamine (DOPE) cholesterol and lipid-anchored polyethylene glycol (PEG) components were combined at a molar ratio of 35%. 16%, 46.5%, and 2.5%, respectively, Pg. 10, second full paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of Kotin by a composition as taught by Billingsley for the purpose of achieving enhanced mRNA delivery (Billingsley, Abstract).
Regarding Claim 6, Kotin discloses the method of claim 1 and further teaches the mean size of the LNPs is about 60-140 nm (lipid nanoparticles have a mean diameter from about 30 nm to about 150, preferably about 100 nm, ¶ 207).
With regards to Claim 9, Kotin discloses the method of claim 1 and further teaches intravenous administration (in utero intravenous infusion, ¶ 234)
With regards to Claim 10, Kotin discloses the method of claim 1 and further teaches delivery with a delivery target specific antibody-conjugated PEG (antibody drug conjugates for targeted therapy, paragraph 183, with PEG modifications, ¶¶ 177-179).
With regards to Claim 11, Kotin discloses the method of claim 10 and further teaches the delivery target is expressed on the surface of an organ cell (promoters enhance recognition for specific organs, ¶ 306).
With regards to Claim 12, Kotin discloses the method of claim 1, and further teaches modification with peptide-conjugated PEG to target a specific organ (see response to claims 9-11 above).
With regards to claim 13 and 14, Korin discloses the method of claim 1, and further teaches improving survival and proliferation of hematopoietic stream and progenitor cells (prostaglandin E2 agonists are taught as immunosuppressants, ¶¶ 201 and 204).
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.
Claims 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/293,419 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they claim a specific genus of ionizable polyamine-lipids. As the genus appears to overlap the instant genus claimed, the instant claims are obvious over the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN J PACKARD whose telephone number is (571)270-3440. The examiner can normally be reached Mon 2-6pm and Tues-Fri 9:30am-6:30pm + mid-day flex.
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/BENJAMIN J PACKARD/ Primary Examiner, Art Unit 1612
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