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 Status
Claims 2, 3, 6, 8, 21-24, 26, 27, 29, 29, 30, 32-36, 38-40, 42-44 and 46 are cancelled.
Claims 1, 4, 5, 7, 9-20, 25, 28, 31, 37, 41, 45 and 47 are pending.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/17/24 follows the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 45 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a disease or disorder in a subject in need thereof, does not reasonably provide enablement for preventing a disease or disorder in a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. While there is no requirement that treatment of a disease or disorder has to be efficacious, Applicant is reasonably enabled to administer the composition to any subject with any disease or any disorder. However, Applicant has failed to demonstrate any ability of the lipid nanoparticles of claim 1 to prevent any and all diseases and disorders. In fact, claim 1 does not even require a pharmaceutical agent that might prevent a disease or disorder. This is problematic due to the wide variety of different diseases and disorders that affect the body. The ordinary artisan in this field has advanced medical knowledge including pharmaceutical formulation and administration, diseases etiology and treatment regimens. The medical arts involve physiological reactions which are inherently unpredictable. MPEP 2164.03: “In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).” Consequently, there is high unpredictability in the art on how to prevent any and all diseases and disorders and Applicant has not provided any guidance on how to do so or provided working examples of preventing any disease or disorder. Applicants is basically proposing testing to see which diseases and disorders can be prevented and is leaving it to the ordinary artisan to figure out how to prevent any and all diseases and disorders with no reasonable expectation of success. Genetech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.” (Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997)).
In order to actually achieve the claimed invention, it is clear from the discussion above that the skilled artisan could not rely upon Applicant's disclosure as required by 35 U.S.C. 112, first paragraph, and would have no alternative recourse but the impermissible burden of undue experimentation in order to practice the full scope of the embodiments presently claimed.
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 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. 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.
Claims 1, 4, 5, 7, 9-20, 25, 28, 31, 37, 41, 45 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Heyes (US20110313017; of record).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims (in part);
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical nucleic acid drug delivery research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical formulation of nucleic acids including component mixtures and excipients— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 4, 5, 7, 19 and 20, Heyes teach in claims 1 and 29-32:
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See also [0413] describing:
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With regard to R3, Heyes further provide broader guidance that the POZ is a polyoxazoline polymer of the structure -[N(COR3)CH2CH2]x -, and POZb is a polyoxazoline polymer of the structure -[N(COR3)CH2CH2]y -, wherein R3 is independently selected for each repeating unit of the polyoxazoline polymer and is a functional group including, but not limited to, unsubstituted or substituted alkyl, alkenyl, aralkyl and heterocycylalkyl. [0017]. See also [0316 and 0318]. Heyes teaches that a substituted alkyl includes -NRxRy and -NRxC(=O)RY where Rx and Ry are the same or different and are independently hydrogen or alkyl [0081]. Heyes teaches an example of R3 as ethyl [0099], which renders obvious at least -CH2-CH2-NH2 when Rx and Ry are hydrogen and reads on the claimed R2 of claim 1 or when the substituted alkyl is -NRxC(=O)RY with Rx being hydrogen or methyl and Ry being the alkyl ethyl of instant claims 7 and 9. Heyes teaches nanoparticle sizes [0339].
Regarding claim 1, Heyes teaches that the cationic lipid is present from about 2 mol% to about 60 mol% or even about 50mol% and about 55 mol% [0281-0282], which overlaps the claimed range of from 45 to 55 mol%.
Regarding claims 10-15, Heyes teach the general formula (I):
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Heyes teach that L is a linker:
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Consequently, the ester, sulphonate, ether and the amides of variable Z in claims 10-15 are obvious variants of Heyes.
Regarding claims 20, 25 and 28, Heyes teach that the non-cationic neutral lipid can be cholesterol (Claim 5; [0289]), which is a sterol, and can be present from about 10 mol% to about 60 mol% [0291] or up to about 40 mol% cholesterol [0292], which provides a range that overlaps the claimed range of 3 to 20 mol%. Heyes also teaches that the non-cationic lipid is a mixture of a phospholipid (neutral lipid) and cholesterol (Claim 6; [0025, 0070]).
Regarding claims 20 and 31, Heyes teach that: “the lipid conjugate (e.g., POZ-DAA conjugate) comprises from about 0 mol % to about 20 mol %, from about 0.5 mol % to about 20 mol %, from about 2 mol% to about 20 mol%...of the total lipid present” [0329], which overlaps the claimed range of from 0.1 mol% to 10 mol% and from 0.1 mol% to 5 mol%.
Regarding claim 37, Heyes teach that the term “nucleic acid” refers to mRNA [0047].
Regarding claim 41, Heyes teaches pharmaceutical compositions and a pharmaceutically acceptable carrier (Claim 36; [0104, 0119, 0357-0358]).
Regarding claims 45 and 47, Heyes teach methods of administering the lipid particle composition to a mammal (Claim 41) where in some embodiments, a mammal (e.g., human) susceptible to developing a particular disease or disorder may be pretreated with one or more doses of nucleic acid-lipid particles containing one or a cocktail of siRNAs as a prophylactic measure for preventing the disease or disorder. [0126] In that context, the composition administered reads on a vaccine. Heyes teach influenza virus nucleic sequences that can be silenced [0169].
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Heyes is that Heyes do not expressly teach Z is -S(CH2)2C(O)-, -Z1-OC(O)-, -Z1-NHC(O)-, -Z1-S(O)2-, and-Z1-OCH2- and the corresponding R3 of claims 10-15. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the lipid nanoparticle composition of Heyes where Z is -S(CH2)2C(O)-, -Z1-OC(O)-, -Z1-NHC(O)-, -Z1-S(O)2-, and-Z1-OCH2- and the corresponding R3 of claims 10-15, and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because Heyes teaches a homolog where Z is -S(CH2)C(O)- and the claimed Z is -S(CH2)2C(O)- is expected to have nearly identical properties. See MPEP 2144.09(II): “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.” Consequently, given the different linkers taught by Heyes, the claimed variable Z appears obvious in the absence of evidence to the contrary. It is then merely routine optimization to select R3 is -NR3aR3b or -CH(R3b)2 for each Z with a reasonable expectation of success. Similarly, the ordinary artisan can readily derive the claimed -N(R2)R2 moiety from the disclosure of Heyes to read on the Formulas IIa and IIb as explained above. Consequently, the claimed poly(alkyloxazoline)-lipid conjugate appears obvious over the disclosure of Heyes.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
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, 4, 5, 7, 9, 14, 20, 25, 28, 31, 37, 41, 45 and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-22 of U.S. Patent No. 12233132. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent teaches species of the claimed lipid compounds and compositions of the lipid nanoparticles in claims 17-22:
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As shown above, the patent teaches when Z is -S(CH2)2C(O)- and when Z is -Z1-OCH2- and Z1 is a covalent bond. The patent does not expressly teach the mol% of the cationic lipid, poly(alkyloxazoline)-lipid conjugate or helper lipid, interpreted to be a neutral lipid since ionizable lipids are already recited, or cholesterol in the composition. However, it is merely routine optimization of the patented components to find the best combination for the lipid nanoparticle composition. See MPEP 2144.05 (II) (A): “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)…see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").
The patent does not expressly teach methods of preventing or treating a disease or disorder by administration of the composition in a pharmaceutically acceptable carrier. However, the purpose of the patented composition is for administration to a subject in need thereof to at least treat a disease or condition. The ordinary artisan would formulate the composition with a pharmaceutically acceptable carrier to do so.
The patent does not expressly teach a vaccine comprising the lipid nanoparticle. However, a vaccine would depend upon the action of the active nucleic acid which can inoculate the subject against a disease or disorder such as the flu. In that case the composition of the lipid nanoparticle would serve to vaccinate the individual and be a vaccine.
Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Harris et al. (US20220249695; published August 11, 2022 with benefit to provisional application 63147470 filed February 09, 2021) teaches compound 15b [0217]:
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However, the provisional application does not appear to support that structure and US20220249695 is not prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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