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 .
Notice of Pre-AIA or AIA Status
DETAILED ACTION
Status of the Claims
Claims 12-13, 15, 17, 21-33, 37-101, 103-126, and 128 are cancelled. Claims 1-11, 14, 16, 18-20, 34-36, 102, and 127 are pending and under examination.
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
The instant application is a national stage entry of PCT/US2022/045408 filed on 9/30/2022, which claims priority from 63/250,932 filed on 9/30/2021.
Information Disclosure Statement
The information disclosure statement filed on 10/22/2024 has been considered by the examiner.
Claim Objections
Claims 1, 2, 4, 6, 7, 19, 20, and 34 are objected to for the phrasing “selected from…..and…” which is more appropriately “selected from…..or….” for the group of options that is no longer in the form of “selected from the group consisting of….and…”.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112(a)
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 127 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 or preventing cancer/tumors, viral infections, or autoimmune diseases, does not reasonably provide enablement for treating any disease, disorder or condition nor preventing diseases, disorders or conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The claim allows for treating or preventing of a disease, disorder or condition by administration of the composition in claim 102. Claim 102 provides for circular RNA polynucleotide in general. This RNA is the active agent, but would require particular forms in order to be used for treating or even possibly preventing diseases, disorders or conditions.
Shi et al. (Signal Transduction and Targeted Therapy, 2024, volume 9, pages 1-43) teaches the progress and prospects of mRNA based drugs in pre-clinical and clinical applications (title and abstract). Shi recognizes that mRNA may be used for a wide range of diseases, however, despite numerous preclinical studies translation of the mRNA medicines is limited (Introduction). Shi sees potential for mRNA to help treat various diseases and that it is currently in early stages of development (page 34). Shi recognizes successful implementation involves modification of the mRNA molecule itself (page 34).
Applicant does have some information regarding using its treatment for providing CARs to mice that help deplete B-cells (page 681 of applicant’s specification). Applicant does also provide for using mRNA encoding mOX40L that provides results in mouse studies (pages 680 and 682 of the specification). The use of CARs, CAR-Tregs, and mOX40L that applicant provides in the specification have shown efficacy in the prior art for treating cancers/tumors and autoimmune disorders. mRNA vaccines are known to be used for vaccines to prevent/confer protection to viral infections (e.g. SARS-CoV-2, applicant example 62, or influenza in example 25). However, outside of discussion of these, there is no evidence of being able to treat other diseases, disorders or conditions. Shi makes evident that using mRNA (RNA) strategies, although promising, require development to be able to treat new diseases/disorders.
Applicant’s specification further provides that treating or preventing do not necessarily imply 100% complete treatment or prevention (paragraph 219 of specification). Applicant also indicates that prevention encompasses delaying onset of a condition or symptom thereof, which means the condition or symptom can occur although with delay. In this way, both treating and prevention are feasible for the diseases, disorders or conditions that applicant provides enablement for. Applicant does not discuss or does not provide examples for many diseases or disorders such as muscular dystrophies, neurodegenerative diseases like Parkinson’s disease, or Cystic fibrosis among many others.
Since the art recognizes that RNA treatment strategies require experimentation and development of new RNA molecules and applicant’s specification only provides for methods of designing RNAs to provide for delivering CARs, CAR-Tregs and antigens/vaccines that would allow treatment of disorders like autoimmune disorders, cancers and viral infections, applicant does not have enablement for the full scope of diseases, disorders and conditions that might be treatable or preventable with such a strategy of applicant. This would require undue experimentation by one of skill in the art (e.g. a medical doctor or medical research scientist) in order to provide the RNAs of various types and methods to treat the vast array of diseases, disorders and conditions that exist. Thus, applicant has enablement for using CAR, CAR-Treg and antigen or vaccine strategies to treat or prevent cancer, an autoimmune disorder or viral infections, but does not have enablement for treating or preventing all the possible diseases, disorders or conditions that would exist.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4 and 6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. R2 and R’ require an imidazolyl group, however, claims 4 and 6 contain rings that are not imidazolyl groups as they have options of rings with nitrogens in positions other than the 1 and 3 positions that are characteristic of imidazole groups. Thus, these claims attempt to expand this group to be groups that are not imidazolyl groups. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11, 14, 16, 18, 20, and 35-36 are rejected under 35 U.S.C. 103 as being unpatentable over Xu WO2021178396A1 (published 9-10-2021 and effective filing date of 3-2-2020, in applicant IDS).
Xu teaches a compound of formula I –
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Xu teaches compounds of formula III on pages 5-8:
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Xu teaches lipidoid nanoparticles comprising this compound plus cholesterol, DOPE or PEG2K-DEPC, and protein or nucleic acid (pages 8-9). The Figure 1A-1C brief description indicates the use of FLuc mRNA. Xu teaches “FIG. 3C shows the results of rough screening of different lipidoid library in primary human CD8+ T lymphocytes using FLuc mRNA. “F” indicates the lipidoids formulated with cholesterol, DOPE and DSPE-PEG to the weight ratio of 16: 4: 1 : 1.” (pages 2-3).
Xu teaches –
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Xu teaches treating disease and effective amounts of compound when administered treat a disease (pages 20-21). Xu teaches in vivo delivery (pages 25 and 29). Xu teaches steriosomers and enantiomers of its compounds (page 22). Xu teaches synthesis and detailed screening of lipidoids containing imidazole and imidazole analogues (pages 27-28).
One of ordinary skill in the art before the time of filing would have provided various imidazole compounds having different lipid groups via divalent linkers with ester bonds and with or without -OH groups by teachings of Xu, which provides for the purposes of carrying mRNA and other compounds for delivery. Xu may not teach specific compounds with one hydroxyl placed as in applicant’s formula 7 or two hydroxyl groups each followed by groups with ester linkages as in applicant’s formula 8, but it does have teachings where a hydroxyl can be placed at one of the given positions and also allows for ester linkages (-C(O)-O-) that can be on both sides of the divalent group having lipid chains. Thus, as Xu provides for structurally similar compounds for the same use of carrying mRNA to a cell or subject with structure and groups (imidazoles, hydroxyls, ester linkages, lipid chains, divalent linking of lipid chains from an alkyl bonded to the imidazole group) of applicant’s claims, one of ordinary skill in the art before the time of filing would have made such compounds with a reasonable expectation of success in obtaining other suitable imidazole containing divalent lipid compounds for mRNA delivery. See MPEP 2144.09 “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)” (MPEP 2144.09 I). Additionally, “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. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious)” (MPEP 2144.09 II). MPEP 2144.09 III provides “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979)”.
Claims 1-11, 14, 16, 18-20, 34-36, 102 and 127 are rejected under 35 U.S.C. 103 as being unpatentable over Xu WO2021178396A1 (published 9-10-2021 and effective filing date of 3-2-2020) in view of Benenato WO2021055833A1 (published 3-25-2021).
Xu teaches the claims as discussed above. Xu teaches a formulation, but no indication of branched lipid chains on its compounds (however, generally teaching of lipids (genus) in Xu).
Xu does not teach the branched chain lipid groups although it allows for the genus of lipid groups in its compounds. Xu teaches RNA/mRNA but does not teach circular RNA.
Benenato teaches lipid nanoparticles that can include RNA for delivery of therapeutics or prophylactics to mammalian cells and/or organs (abstract). Benenato teaches various compounds having divalent structure and containing branched lipid chains (claim 13 of Benenato, also claim 4 of Benenato). Benenato teaches circular RNA (paragraph 152 and embodiment 130). Benenato teaches various lipid nanoparticles having cholesterol and PEG lipid (see embodiments 154-173). Benenato teaches :
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(abstract) and
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.
One of ordinary skill in the art before the time of filing would have been able to modify imidazole-lipid compounds of Xu with branched lipid groups as well as straight chain lipid groups as these are seen as forms for making lipid nanoparticles by the prior art teachings of Benenato. Benenato also sees circular RNAs as a form of RNA for delivery by modified lipid nanoparticles. Thus, there was a reasonable expectation of success of making compounds and compositions of applicant’s claims by the combined teachings of Xu and Benenato with the expectation of delivering RNA including circular RNA molecules for treatments. See MPEP 2144.09 “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)” (MPEP 2144.09 I). Additionally, “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. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious)” (MPEP 2144.09 II). MPEP 2144.09 III provides “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979)”.
Conclusion
No claims are allowed.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613