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 .
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.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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.
Claims 74-75 are 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 administering the recited composition, does not reasonably provide enablement for treating a disease 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.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. See MPEP 2164.01(a). The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by MPEP 2164.01(a) and are set forth below.
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved; see MPEP 2164.03. Keeping that in mind, the factors set forth in MPEP 2164.01 are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill level (B)-(E)
The invention relates to a method for treating the full scope of diseases, apparently with only the recited ionizable cationic lipid and without a therapeutic agent. The relative skill of those in the art is high, that of an MD or PhD. That factor is outweighed; however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites Silvennoinen et al. (US 2012/0309023 A1), which teaches the following as of paragraph 0070, which is reproduced below.
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The last sentence of the above-reproduced paragraph indicates that there are human diseases which lack a clinically approved treatment. Tas (US 2024/0384291 A1) also teaches the existence of frequent diseases of aging lacking a previously known satisfactory treatment, as of paragraph 0091.
As such, there would have been no reasonable explanation that the full scope of diseases could have been treated in the absence of undue experimentation.
The breadth of the claims (A)
Claims 74-75 are broad for the following reasons. First, claims 74-75 recite all known diseases, and do not limit the scope of the disease treated. Secondly, claims 74-75 do not appear to require a therapeutic agent. In fact, the only agents required by claims 74-75 appear to be the cationic lipid of claim 1 and a pharmaceutically acceptable excipient.
3. The amount of direction or guidance provided and the presence or absence of working examples (F)-(G)
The instant specification includes multiple examples. Many of the examples are synthetic methods for synthesizing the recited lipids and do not relate to methods of treatment. However, the specification does disclose an example related to knock down of Factor VII, as of pages 262-263 of the specification as filed. Factor VII is a clotting factor; therefore, knockdown of Factor VII would appear to result in anticoagulant activity. As such, the instant specification does appear to enable administration of siRNA to achieve anticoagulation via knockdown of Factor VII using the administered siRNA. However, anticoagulants are known in the art, and the administration of anticoagulants does not treat the full scope of diseases.
The specification provides no direction or guidance for practicing the claimed invention in its “full scope”. No reasonably specific guidance is provided concerning useful therapeutic protocols for the treatment of the full scope of diseases, other than anticoagulation in the above-discussed example. The latter is corroborated by the working examples.
4. The quantity of experimentation necessary (H)
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used to treat the full scope of diseases as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the claimed invention in its “full scope” a person of ordinary skill in the art would have to engage in undue experimentation, with no reasonable expectation of success.
5. Enabled Subject Matter:
The examiner suggests the following amendment to claim 74 to overcome this issue.
Claim 74 (Proposed Amendment): A method of treating a disease in a subject in need thereof, comprising administering a therapeutically effective amount of a nucleic acid capable of treating said disease to the subject in combination with the pharmaceutical composition of claim 66.
As an initial matter, this proposed amendment is intended to overcome only the applied rejection for lack of enablement. It is not intended to overcome any other rejection. This proposed amendment overcomes the issue of lack of enablement because it limits the claims to administration of a nucleic acid already capable of treating the disease to be treated. It clarifies that the inventive concept is using the pharmaceutical composition of claim 66 to assist in administration of a nucleic acid with therapeutic effect that already would have been enabled for treating the relevant disease. As such, the combination of the nucleic acid and the pharmaceutical composition of claim 66 is enabled for treating said disease.
Claim Rejections - 35 USC § 102(a)(2) – Anticipation
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)(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.
Claim(s) 1, 3, 8, 16-17, 20, 22, 28, 36-39, 42, 67, and 74 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rajappan et al. (US 2023/0295081 A1).
Claim(s) 1, 3, 8, 16-17, 20, 22, 28, 36-42, 52, 54-56, 61, 66-67, 71-72 and 74-76 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rajappan et al. (WO 2023/086514 A1).
Rajappan et al. (hereafter referred to as Rajappan ‘081 and Rajappan ‘514) teaches the following chemical structure as of the abstract, which is reproduced below.
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Rajappan ‘081 also teaches the following structure on page 10, left column, which is broader than that which is in the abstract.
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The Rajappan references teach chemical structures in which Y is either -N-C(O)S or an ester, as of e.g. Rajappan ‘081, page 46, relevant chemical structures reproduced below.
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These would appear to read on the claimed structure wherein R1 and R2 are methyl groups, L1 is a saturated C3 alkylene group, Y is either -CH2-O-C(O)- or N-C(O)-S, L2 and L3 are saturated C3 alkylene groups, L4 and L5 are absent, R3 and R4 are hydrogen, L6, L7, L8, and L9 are methylene groups, and R5-8 are a particular branched alkyl group in the structure on the left and an alkyl substituted aryl group on the right.
As to claim 3, the above-reproduced structures teach the required Y groups.
As to claim 8, the above-reproduced structures of Lipids 40 and 41 teach R1 and R2 as C1 alkyl groups.
As to claims 16-17, the above-right reproduced structure would appear to be a C6 aryl group substituted with both a C1 alkyl group and a C4 branched alkyl group.
As to claim 20, the above-reproduced structures of Lipids 40 and 41 would appear to teach a linear unsubstituted C3 alkylene as L1.
As to claim 22, the above-reproduced structures of Lipids 40 and 41 would appear to teach a linear unsubstituted C3 alkylene as L2 and L3.
As to claim 28, the above-reproduced structures of Lipids 40 and 41 appear to teach L6, L7, L8, and L9 as a methylene group and L4 and L5 absent.
As to claim 36, Rajappan ‘081 teaches the following on page 268, relevant text reproduced below.
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The above-reproduced text would appear to read on the required composition as of claim 112 of Rajappan. Also see Rajappan ‘514, pages 335-339, which appear to have essentially the same teachings.
As to claim 37, Rajappan ‘081 teaches siRNA, mRNA, and other forms of RNA s of claim 113 of Rajappan ‘081 and Rajappan ‘514.
As to claim 38, Rajappan ‘081 teaches encoding a therapeutic protein as of claim 113 of Rajappan ‘081. Also see claim 114 of Rajappan ‘514.
As to claim 39, Rajappan ‘081 teaches encoding an enzyme, antibody, antigen etc. on the above-reproduced text. Also see claim 115 of Rajappan ‘514.
As to claim 40, Rajappan ‘514 teaches encoding a gene editing enzyme on page 336, relevant text reproduced below.
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As to claim 41, Rajappan ‘514 teaches encoding CRISPR, TALEN, meganuclease, as of claim 127 of Rajappan ‘514.
As to claim 42, Rajappan ‘081 teaches a liposome in claim 118 and Rajappan ‘514 teaches a liposome in claim 118.
As to claim 52, Rajappan ‘514 teaches a lipid nanoparticle containing DOPE, DSPC, or other excipients, as of Rajappan ‘514, page 336.
As to claim 54, Rajappan ‘514 teaches cholesterol as of claim 130.
As to claim 55, Rajappan ‘514 teaches a PEG-lipid conjugate as of claim 131.
As to claim 56, Rajappan ‘514 teaches the following on page 337, relevant text reproduced below.
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This would appear to be within the claim scope.
As to claim 61, Rajappan ‘514 teaches lipid to nucleic acid weight ratio of about 50:1 to about 10:1 as of claim 137.
As to claim 66, Rajappan ‘514 teaches a pharmaceutical composition as of claim 142, as does Rajappan ‘081.
As to claim 67, Rajappan ‘514 teaches a lyophilized pharmaceutical composition as of claim 143, as does Rajappan ‘081.
As to claim 71, Rajappan ‘514 teaches cryoprotectants as of claim 147.
As to claim 72, Rajappan ‘514 teaches sucrose and glycerol as of claim 149.
As to claim 74, Rajappan ‘514 teaches a method of treating a disease as of claim 150. Rajappan ‘081 teaches this as of claim 150.
As to claim 75, Rajappan ‘514 teaches intravenous or intramuscular administration, as of page 338, claim 151.
As to claim 76, Rajappan ‘514 teaches the following as of page 339, relevant text reproduced below.
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Claim 152 of Rajappan ‘514 is understood to read on the required claim 76. Also, claim 152 of Rajappan ‘081 also reads on this requirement.
As to claim 77, Rajappan ‘514 teaches this, as of claim 153.
As to claim 78, Rajappan ‘514 teaches this, as of claim 154.
The examiner clarifies that the reason that certain claims are rejected as anticipated by Rajappan ‘514 but not as anticipated by Rajappan ‘081 is because the claims of Rajappan ‘514 recite subject matter not recited by the claims of Rajappan ‘081 (though other than the claims, the disclosures of Rajappan ‘514 and Rajappan ‘081 appear to be identical). The examiner has considered subject matter in the claims as being suitable for citation in an anticipation rejection. In contrast, the examiner has considered broad disclosure in the specification of either Rajappan reference as subject matter suitable to cite in an obviousness rejection but not suitable to cite in an anticipation rejection because of too much “picking and choosing.” In the case of anticipation rejections, the elements must be arranged as required by the claim; see MPEP 2131, second paragraph in section. A teaching of a claimed element in a long list in the disclosure is not understood to meet this requirement for anticipation rejections because of too much “picking and choosing.” However, a prior art teaching of a claimed element in the broad disclosure of a prior art reference should be cited in the case of an obviousness rejection; see MPEP 2123 and 2143, Exemplary Rationale A; see also the obviousness rejection below.
Note Regarding Reference Date: The instant application appears to have an earliest effective filing date of 10 May 2023 based upon priority to a provisional application. Both Rajappan references appear to have been published after 10 May 2023, and are therefore not prior art under AIA 35 U.S.C. 102(a)(1). However, both Rajappan references appear to have been effectively filed earlier than the effective filing date of the instant application, rendering these references prior art under AIA 35 U.S.C. 102(a)(2).
The examiner notes that there appear to be common inventors of the instant application and of both Rajappan references. Nevertheless, there are individuals named as inventors of both Rajappan references such as Amit Sagi, Priya Prakash Karmali, and Padmanabh Chivukula, who are not inventors of the instant application. As such, the inventive entity of both prior art references differs from that of the instant application.
To qualify as prior art under AIA 35 U.S.C. 102(a)(2), the prior art U.S. patent, U.S. patent application publication, or WIPO published application ("U.S. patent document") must "name[ ] another inventor." This means that if there is any difference in inventive entity between the prior art U.S. patent document and the application under examination or patent under reexamination, the U.S. patent document satisfies the "names another inventor" requirement of AIA 35 U.S.C. 102(a)(2). Thus, in the case of joint inventors, only one joint inventor needs to be different for the inventive entities to be different. Even if there are one or more joint inventors in common in a U.S. patent document and the later-filed application under examination or patent under reexamination, the U.S. patent document qualifies as prior art under AIA 35 U.S.C. 102(a)(2) unless an exception in AIA 35 U.S.C. 102(b)(2) is applicable. See MPEP 2154.01(c). As such, both Rajappan references are understood to be prior art under AIA 35 U.S.C. 102(a)(2) and the above-applied rejections are understood to be proper.
Applicant is encouraged to review MPEP 2154.02 and 2155 for information regarding the possibility of invoking an AIA exception in order to overcome the above-applied anticipation rejections.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1, 3, 7-8, 15-16, 20, 22, 27-30, 34-42, 52, 54-55, 58, 61, 66-67, 71-72, and 74-78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajappan et al. (US 2023/0295081 A1).
Claim(s) 1, 3, 7-8, 15-16, 20, 22, 27-30, 34-42, 52, 54-55, 58, 61, 66-67, 71-72, and 74-78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rajappan et al. (WO 2023/086514 A1).
Rajappan ‘081 is drawn to an ionizable cationic lipid with the following structure, as of Rajappan ‘081, page 10, relevant figure reproduced below.
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Rajappan ‘081 teaches the meaning of the indicated variables as of paragraphs 0117-0142.
As to claim 1, purely en arguendo and for the purposes of this ground of rejection only, the examiner understands Rajappan ‘081 to teach all of the claimed requirements, though not in the same embodiment. As such, while the prior art teaches all of the claimed components, the prior art is not anticipatory insofar as these components must be selected from various lists/locations in the prior art reference. It would have been prima facie obvious; however, to have selected the recited components from various lists/locations in the prior art reference and to have combined them together. This is because such a modification would have represented nothing more than the predictable use of prior art components according to their established functions. Combining separate prior art components (from a single prior art reference) according to known methods to yield predictable results is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 3, Rajappan ‘081 teaches the required features on page 10, paragraph 0152.
As to claim 7, Rajappan ‘081 teaches this requirement as of paragraph 0174.
As to claim 8, Rajappan ‘081 teaches R1 and R2 as methyl groups in the structure of Lipid 41 on page 240.
As to claim 15, Rajappan ‘081 teaches R5-8 as linear alkyl groups as of the structure of lipid 33 on page 217.
As to claim 16, Rajappan ‘081 teaches R5-8 as aryl groups as of the structure of lipid 34 on page 218.
As to claim 20, in the structure of Rajappan ‘081, page 218, structure 34, there is a linear C3 alkylene group for L1.
As to claim 22, in the structure of Rajappan ‘081, page 218, structure 34, there are linear C3 groups for L2 and L3.
As to claims 27-30, Rajappan ‘081 teaches the following on page 10, relevant text reproduced below.
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In view of this teaching, the skilled artisan would have been motivated to have modified the compound of Rajappan ‘081 to have achieved the invention claimed by claims 27-30.
As to claim 34, the examiner has provided the following diagram showing claimed lipid 42 side-by-side with Lipid 10 of page 20 of Rajappan ‘081, which are reproduced below side-by-side.
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The above two structures appear to be the same other than the functionalities of R5-8, which is a 2-cyclohexyl ethyl group in the prior art and a 2-biphenyl ethyl group in the claimed invention. Nevertheless, elsewhere in the Rajappan ‘081 reference, Rajappan ‘081 teaches that R5-8 may be an alkyl group substituted with an aryl moiety or an aryl moiety itself, as of Rajappan ‘081, paragraphs 0030 and 0033. Rajappan ‘081 then defines the term “aryl” to include a biphenyl moiety, as of Rajappan ‘081, paragraph 0049. As such, the skilled artisan would have been motivated to have substituted a biphenyl group in place of the cyclohexyl group of page 20 of Rajappan ‘081 for predictable formation of an ionizable cationic lipid with a reasonable expectation of success.
As to claim 35, the examiner notes that conflicting claim 1 recites the following lipid 12 from page 24 of Rajappan ‘081, which is reproduced below next to recited lipid 46
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The differences between these structures appear to be that:
L4 and L5 are absent in the structure of Rajappan ‘081 reproduced above, but are a C1 alkylene group in the instantly claimed structure; and
L2 and L3 are C5 alkylene groups in the structure of Rajappan ‘081 reproduced above, but are C3 alkylene groups in the structure of the conflicting claims.
Nevertheless, Rajappan ‘081 teaches that L4 and L5 may be absent and that L2 and L3 may be alkylene groups between C1 and C8, the skilled artisan would have been motivated to have modified the structure of Rajappan ‘081 to have obtained the instantly claimed structure.
As to claim 36, Rajappan ‘081 teaches a lipid nanoparticle as of at least paragraph 0304.
As to claim 37, Rajappan ‘081 teaches incorporation of a mRNA or siRNA, as of paragraph 0295.
As to claim 38, Rajappan ‘081 teaches a mRNA or self replicating RNA comprising a coding region that encodes a therapeutic protein of interest, as of paragraph 0295.
As to claims 39-41, Rajappan ‘081 teaches the following, as of paragraph 0295, relevant text reproduced below.
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Rajappan ‘081 teaches a gene editing enzyme e.g. for CRISPR in the above-reproduced text.
As to claim 42, Rajappan ‘081 teaches a liposome, lipoplex, or lipid nanoparticle in the above-reproduced text.
As to claim 52, Rajappan ‘081 teaches a non-cationic lipid such as DSPC or DOPE in paragraphs 0449-0450.
As to claim 54, Rajappan ‘081 teaches cholesterol in paragraph 0452.
As to claim 55, Rajappan ‘081 teaches a PEG-lipid conjugate in paragraph 0364.
As to claim 58, Rajappan ‘081 appears to teach the required percentages of components in paragraphs 0365-0366.
As to claim 61, Rajappan ‘081 teaches the required lipid to nucleic acid weight ratio in paragraphs 0367-0368.
As to claim 66, Rajappan ‘081 teaches a pharmaceutical composition with a pharmaceutically acceptable excipient in at least paragraph 0471.
As to claim 67, Rajappan ‘081 teaches a lyophilized composition as of paragraphs 0300, 0479, and 0480.
As to claims 71-72, Rajappan ‘081 teaches a cryoprotectant that is glycerol in paragraph 0480.
As to claim 74, Rajappan ‘081 teaches a method of treating a disease in paragraphs 0489-0490.
As to claim 75, Rajappan ‘081 teaches intravenous and intramuscular administration in paragraph 0489.
As to claim 76, Rajappan ‘081 teaches expressing polynucleotides in paragraph 0384. Rajappan ‘081 teaches mRNA expression in paragraphs 0469 and 0477, as well as paragraph 0934, in which expression in a target cell is taught.
As to claim 77, Rajappan ‘081 teaches expression of an antigen to provide an in vivo immunogenic response.
As to claim 78, Rajappan ‘081 teaches nucleic acid encapsulation followed by delivery in paragraph 0305.
Regarding Rajappan ‘514, the teachings of this reference appear to be the same as those of Rajappan ‘081 other than in the claims of either Rajappan ‘514 and Rajappan ‘081. As such, the instant claims are rejected over Rajappan ‘514 for essentially the same reason that they are rejected over Rajappan ‘081.
Non-Statutory 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, 3, 7-8, 15-16, 20, 22, 27-30, 35-39, and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,723,023. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a compound with the chemical structure:
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Conflicting claim 1 is drawn to a compound with the following chemical structure.
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The instant and conflicting claims differ because there are different requirements regarding the chemical identities of groups R5-8. Specifically, the conflicting claims recite various fluorine containing groups that are not recited by the instant claims. Additionally, the instant claims recite heteroaryl groups for R5-8 that do not appear to be explicitly recited by the instant claims.
Nevertheless, the conflicting claims recite specific chemical structures, as of conflicting claim 15. These appear to be within the scope of instant claim 1. These chemical structures appear to effectively anticipate that of claim 1, thereby resulting in a prima facie case of anticipatory-type non-statutory double patenting with respect to claim 1.
As to instant claim 3, the required Y groups appear to have been recited by conflicting claims 1 and 2.
As to instant claim 7, the examiner notes that conflicting claim 1 recites the following.
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This would appear to overlap with the requirements of instant claim 8.
As to instant claim 8, the linear C1-6 alkylene of the instant claims would appear to overlap with this requirement.
As to instant claims 15-16 regarding the aryl substituted linear alkyl group, the examiner notes that the conflicting claims recite the following, as of conflicting claim 1, column 514, relevant text reproduced below.
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Item (a)(iv) would appear to read on the instantly claimed requirements.
As to claim 20, all of the structures recited by conflicting claim 15 appear to have a linear unsubstituted alkylene group at the position of L1, which is a C3 alkylene group in multiple cases.
As to claim 22, the first two structures recited by conflicting claim 15 appear to have linear C3 alkylene groups at the positions of L2 and L3.
As to claims 27-30, the examiner notes that conflicting claim 1 recites the following:
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The skilled artisan would have been motivated to have formulated the options recited by instant claims 27-30 from the above-reproduced claim requirements.
As to instant claim 35, the examiner notes that conflicting claim 1 recites the following lipid 12, which is reproduced below next to recited lipid 52 of the instant claims
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The differences between these structures appear to be that:
L4 and L5 are absent in the structure of the conflicting claims but are a C1 alkylene group in the instantly claimed structure; and
L2 and L3 are C5 alkylene groups in the structure of the conflicting claims but are C3 alkylene groups in the structure of the conflicting claims.
Nevertheless, as conflicting claim 1 recites that L4 and L5 may be absent and that L2 and L3 may be alkylene groups between C1 and C8, the skilled artisan would have been motivated to have modified the structure of the conflicting claims to have obtained the instantly claimed structure.
As to instant claim 36, the required lipid composition is recited by conflicting claim 26.
As to instant claim 37, the required mRNA, siRNA, or other nucleic acids are recited by conflicting claim 27.
As to instant claim 38, the required mRNA, siRNA, or other nucleic acids that encode a therapeutic protein of interest are recited by conflicting claim 27.
As to instant claim 39, it is noted that conflicting claim 28 recites that the therapeutic protein of interest is an enzyme, antibody, antigen, or others.
As to instant claim 66, conflicting claim 31 recites a pharmaceutical composition.
As to instant claim 67, conflicting claim 32 recites a lyophilized composition.
Claims 36-39, 42, 52, 54-55, 58, 61, 66-67, 71-72, and 74-78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,723,023 in view of Ciaramella et al. (US 2017/0340725 A1).
The instant claims are drawn to a particular cationic lipid as well as lipid nanoparticles comprising said cationic lipid.
The conflicting claims are drawn to a particular cationic lipid as well as lipid nanoparticles comprising said cationic lipid.
The conflicting claims do not recite various features recited by the instant claims such as the additional lipids in the lipid nanoparticle. Conflicting claim 27 recites RNA vaccines.
Ciaramella et al. (hereafter referred to as Ciaramella) is drawn to RNA vaccines and compositions comprising said vaccines, as of Ciaramella, title and abstract. Ciaramella teaches a lipid nanoparticle comprising a cationic lipid which may be an ionizable cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid in paragraph 0073.
Ciaramella does not teach that a cationic lipid with the recited structure.
It would have been prima facie obvious for one of ordinary skill in the art to have substituted the lipid of the conflicting claims in place of the lipid of Ciaramella in the composition of Ciaramella. The conflicting claims are drawn to an ionizable cationic lipid usable in a lipid nanoparticle for delivering mRNA. Ciaramella is also drawn to a lipid nanoparticle for delivering mRNA that includes an ionizable cationic lipid. As such, the skilled artisan would have been motivated to have substituted the ionizable cationic lipid of the conflicting claims in place of that of Ciaramella in order to have predictably formed a lipid nanoparticle for predictable delivery of mRNA such as in a mRNA vaccine with a reasonable expectation of success. The simple substitution of one known element (e.g. the ionizable cationic lipid of the conflicting claims) in place of another (the ionizable cationic lipid of Ciaramella) to achieve predictable results (e.g. delivery of mRNA) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to instant claim 36, the required lipid composition is recited by conflicting claim 26.
As to instant claim 37, the required mRNA, siRNA, or other nucleic acids are recited by conflicting claim 27.
As to instant claim 38, the required mRNA, siRNA, or other nucleic acids that encode a therapeutic protein of interest are recited by conflicting claim 27.
As to instant claim 39, it is noted that conflicting claim 28 recites that the therapeutic protein of interest is an enzyme, antibody, antigen, or others.
As to instant claim 42, Ciaramella teaches liposomes, lipoplexes, and lipid nanoparticles as of paragraph 0428.
As to instant claim 52, Ciaramella teaches DSPC, DOPE, POPC, and other helper lipids in paragraph 0409.
As to instant claim 54, Ciaramella teaches cholesterol in paragraph 0409.
As to instant claim 55, Ciaramella teaches PEG-cDMA and other PEG-lipid conjugates in paragraph 0409.
As to instant claim 58, Ciaramella teaches 25-75% cationic lipid, 0.5-15% of neutral lipid (e.g. helper lipid), 5-50% of sterol, and 0.5-20% of PEG-lipid conjugate on a molar basis, as of paragraph 0410 of Ciaramella. This would appear to overlap with the claimed requirements. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to instant claim 61, Ciaramella teaches a weight ratio of RNA to lipids of 10:1 to 25:1 in paragraph 0403. This appears to be within the claim scope.
As to instant claim 66, conflicting claim 31 recites a pharmaceutical composition.
As to instant claim 67, conflicting claim 32 recites a lyophilized composition.
As to instant claims 71-72, Ciaramella teaches sucrose in paragraph 0426. Although Ciaramella does not identify sucrose as a cryoprotectant, the skilled artisan would have understood sucrose to have acted as a cryoprotectant because it is the same compound as required by the instant claims.
As to instant claim 74, Ciaramella teaches treating a disease as of at least paragraph 0014.
As to instant claim 75, Ciaramella teaches intramuscular administration in paragraph 0097.
As to instant claim 76, Ciaramella teaches expression of RNA polynucleotides encoding structural proteins in paragraph 0045.
As to claim 77, Ciaramella teaches eliciting of immunogenic activity in paragraph 0045.
As to claim 78, Ciaramella teaches mRNA encapsulated by a lipid nanoparticle as of paragraphs 0138 and 0482. Ciaramella then teaches administration of the particle as of at least paragraph 0024.
Claims 36-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 12,723,023 in view of Lee et al. (US 2018/0148719 A1).
The instant claims are drawn to a particular cationic lipid as well as lipid nanoparticles comprising said cationic lipid.
The conflicting claims are drawn to a particular cationic lipid as well as lipid nanoparticles comprising said cationic lipid.
The conflicting claims do not recite various features recited by the instant claims such as delivery of CRISPR components.
Lee et al. (hereafter referred to as Lee) is drawn to lipid nanoparticles delivering guide RNA for CRISPR, as of Lee, title, abstract and paragraph 0004. The composition of Lee includes a cationic lipid, as of Lee, paragraph 0005. Lee also teaches mRNA encoding Cas9 protein as of paragraph 0006.
Lee does not teach a cationic lipid with the recited structure.
It would have been prima facie obvious for one of ordinary skill in the art to have substituted the lipid of the conflicting claims in place of the lipid of Lee. The conflicting claims are drawn to a cationic lipid usable in a lipid nanoparticle for delivering nucleic acids. Lee is also drawn to a lipid nanoparticle for delivering nucleic acids for gene editing that includes a cationic lipid. As such, the skilled artisan would have been motivated to have substituted the cationic lipid of the conflicting claims in place of that of Lee in order to have predictably formed a lipid nanoparticle for predictable delivery of gene editing components with a reasonable expectation of success. The simple substitution of one known element (e.g. the cationic lipid of the conflicting claims) in place of another (the cationic lipid of Lee) to achieve predictable results (e.g. delivery of gene editing components) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to instant claim 36, the required lipid composition is recited by conflicting claim 26.
As to instant claim 37, the required mRNA, siRNA, or other nucleic acids are recited by conflicting claim 27.
As to instant claim 38, the required mRNA, siRNA, or other nucleic acids that encode a therapeutic protein of interest are recited by conflicting claim 27.
As to instant claim 39, it is noted that conflicting claim 28 recites that the therapeutic protein of interest is an enzyme, antibody, antigen, or others.
As to instant claims 40-41, Lee teaches delivery of mRNA encoding a Cas9 enzyme, as of paragraph 0006. This Cas9 enzyme is useful for CRISPR, as of Lee, paragraph 0017.
As to claim 42, Lee teaches lipid nanoparticles as of the reference title.
Claims 1, 3, 7-8, 15-16, 20, 22, 27-30, 35-42, 52, 54-55, 58, 61, 66-67, 71-72, and 74-78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-154 of copending Application No. 19/711,592 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a compound with the chemical structure:
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Copending claim 1 is drawn to a compound with the formula
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The instant and copending claims differ because R5-R8 in the instant claims may be heterocylic groups, which are not recited by the copending claims, and because the copending claims recite options not recited by the instant claims such as fluorinated R5-R8 groups. As such, there are differences between the instant and copending claims. Nevertheless, the cases whereby R5-R8 are unsubstituted alkyl groups is recited by both the instant and copending claims. This subject matter would appear to effectively anticipate the instantly claimed invention, thereby resulting in a prima facie case of anticipatory-type non-statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Relevant Prior Art – No Rejection
As relevant art, the examiner cites Payne et al. (US 2018/0169268 A1). Payne et al. (hereafter referred to as Payne) teaches the following subject matter in the abstract, which is reproduced below.
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The abstract indicates that R1 in the above-reproduced structure is a branched chain alkyl group, and R2 is a linear alkyl group.
Payne differs from the instantly claimed invention at least because the compound of Payne has significantly fewer carbonyl groups than the structure of formula (I) in claim 1. The structure of formula (I) in claim 1 has six carbonyl groups plus the “Y” group that may be a seventh carbonyl group. In contrast, the above-reproduced structure has only three carbonyl groups. As such, the structure of Payne differs from the claimed invention for at least this reason.
As additional relevant prior art, the examiner cites Karmali et al. (US 2023/0320995 A1). Karmali teaches the following chemical structure as of page 4, paragraph 0061, which is reproduced below next to the claimed structure with annotation by the examiner.
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In the above-reproduced structure, the above-indicated carbonyls are oriented such that the ester oxygen faces the nitrogen atom upon the branches converge (to the right of the structure) and the carbonyl carbon faces the point where the branches diverge (to the left of the structure). In contrast, in the claimed invention, the carbonyl groups at this point (which are between L2 and L4, and between L3 and L5) are oriented such that the carbonyl carbon faces the “Y” group where the branches converge (at the right of the structure) and the ester oxygen faces the diverging branches (to the left of the structure). As such, the carbonyls of Karmali are oriented backwards as compared with the claimed invention. There would have been no motivation for the skilled artisan to have reversed the orientation of the carbonyls; as such, no rejection over Karmali has been written by the examiner
Allowable Subject Matter
Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 17 requires that R5-8 are heteroaryl groups. The examiner understands the term “heteroaryl” to refer to an aromatic, heterocyclic group, which refers to a ring containing multiple different types of atoms that follows the Huckel rule relating to aromaticity. This does not appear to have been taught by the prior art. The examiner presents the following rationale in support of this position.
As relevant prior art, the examiner cites Rajappan et al. (US 2023/0295081 A1). Rajappan ‘081 is discussed in detail above, as it teaches the following chemical structure, as of page 10, relevant structure reproduced below from paragraph 0143.
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Rajappan ‘081 differs from the claimed invention because Rajappan ‘081 defines the variables R5-8 differently from how these variables are defined in the instant claims. Specifically, Rajappan ‘081 defines these groups as monocycloalkyl groups, bicycloalkyl groups, or aryl groups, as of Rajappan ‘081, paragraphs 0166-0168, or alkyl groups substituted with monocycloalkyl groups, bicycloalkyl groups, or aryl groups, as of Rajappan ‘081, paragraphs 0163-0165. However, applicant appears to define “aryl” as including only carbocyclic groups and not heterocyclic groups, as of paragraph 0049, reproduced below.
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This definition appears to limit the term “aryl” to groups only containing carbon and hydrogen in the ring. As such, Rajappan does not appear to teach a heteroaryl group at this position.
The examiner notes that Rajappan does teach multiple heterocycles as of page 12, paragraphs 0180 and 0181. However, these heterocycles are drawn to R1 and R2, which is at the opposite end of the molecule as compared with R5-8. The teachings on page 12 of Rajappan ‘081 would not have motivated the skilled artisan to have made R5-8 into heteroaryl groups. Also, the heterocycles taught by page 12 of Rajappan ‘081 are not aromatic and are not heteroaryl groups.
The examiner notes that Rajappan ‘081 teaches lipids on page 44, left column, that include aryl groups at the R5-8 positions; however, these aryl groups are benzene rings and do not include atoms other than carbon in the ring and therefore not heteroaryl groups.
The examiner notes that if applicant chooses to amend the limitations of claim 17 into claim 1, then applicant will have to cancel claims 15-16, lipid 42 in claim 34, and would have to cancel claim 35 to avoid rejections under 35 U.S.C. 112(b) or 112(d). This is because none of the recited lipids in claim 35 have a heteroaryl group at R5-8.
Conclusion
Less than all claims are in condition for allowance.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
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