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 . Claims included in prosecution are claims 4-9, 12-15, 17-20, 37-39, 42-46, and 48.
Restriction Requirement
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 1-3, 36, 49-50, and 52, drawn to a method of treating a cancer comprising administering a nanoparticle comprising a double-stranded DNA (dsDNA) and a cancer vaccine or a cancer therapeutic agent.
Group II, claim(s) 4-9, 12-15, 17-20, 37-39, 42-46, and 48, drawn to a method of treating leukemia or melanoma comprising administering a nanoparticle comprising double-stranded DNA (dsDNA).
Group III, claim(s) 22, drawn to a method of treating a cancer comprising administering a nanoparticle comprising a double-stranded DNA (dsDNA) and a checkpoint inhibitor.
Group IV, claim(s) 56-57, drawn to a lipid nanoparticle.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-IV lack unity of invention because even though the inventions of these groups require the technical feature of a method of treating a cancer comprising administering a nanoparticle comprising double-stranded DNA (dsDNA), this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Mitchell et al. (WO 2021/077066, Apr. 22, 2021) (hereinafter Mitchell) in view of Dutreix et al. (US 7,595,302, Sep.29,2009) (hereinafter Dutreix).
Mitchell discloses lipid nanoparticle compositions used to deliver various nucleic acid molecules and/or therapeutic agents to selected targets to prevent or treat diseases or disorders in a subject in need thereof (Abstract). In some embodiments the target is tumor cells and methods of treating/prevention target cancer (Pg. 9). In one embodiment, the nucleic acid molecule is a DNA molecule (Pg. 45). Cancers to be treated by the methods of treatment include leukemia and melanoma (Pg. 84).
Mitchell differs from the instant claims insofar as not disclosing wherein the lipid nanoparticle comprises double stranded DNA that is at least 45 base pairs in length.
However, Dutreix discloses double-stranded nucleic acid fragments having preferably 8-500 bp which are used to DNA repair induced lethality (DRIL in short) of tumoral cells/tissues (Abstract). The tumor sensitivity to direct or indirect DNA damaging anticancer therapies can be
enhanced by using double stranded nucleic acid molecules (col 2, line 50-53). They can be made linear or made of hairpin double stranded nucleic acids in which the loop can be nucleic acids (satisfies claim 42) (col 3, line 42-43). DRIL molecules can be made of at least one free dsDNA end (col 3, line 47-48). The method for promoting tumor sensibility to anticancer therapies comprises coupling the treatment with DRIL molecules with a double chemotherapy (col 5, line 30-31). In certain embodiments, the DRIL molecules are not chemically modified and correspond to native nucleic acid fragments (col 5, line 41-43).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant claims, to have modified the method of Mitchell to comprise the double stranded DNA of Dutreix motivated by the desire to enhance the tumor sensitivity to direct or indirect DNA damaging anticancer therapies as taught by Dutreix.
Alternatively, generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Mitchell discloses wherein the lipid nanoparticle comprises nucleic acids. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the composition of Mitchell to comprise double stranded DNA, since it is a known nucleic acid for use in treating cancers as taught by Dutreix.
In view of this document, the common technical feature linking Groups I-IV does not constitute a special technical feature as defined by PCT Rule 13.2, as it does not define a contribution over prior art for the reasons set forth above.
During a telephone conversation with Sheldon Heber on Aug. 4, 2026 a provisional election was made without traverse to prosecute the invention of Group II, claims 4-9, 12-15, 17-20, 37-39, 42-46, and 48. Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-3, 22, 36, 49-50, 52, and 56-57 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
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.
1. Claims 37-39 and 42 are 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.
Claim 37 recites the limitation "said dsDNA region" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 4 from which claim 37 depends make no mention of such a “region”.
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.
1. Claim(s) 4-6, 38-39, 42, and 44-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al. (WO 2021/077066, Apr. 22, 2021) (hereinafter Mitchell) in view of Dutreix et al. (US 7,595,302, Sep.29,2009) (hereinafter Dutreix).
Mitchell discloses lipid nanoparticle compositions used to deliver various nucleic acid molecules and/or therapeutic agents to selected targets to prevent or treat diseases or disorders in a subject in need thereof (Abstract). In some embodiments the target is tumor cells and methods of treating/prevention target cancer (Pg. 9). In various embodiments, the LNP further comprises at least helper lipid (Pg. 38). Suitable helper lipids include phospholipid, cholesterol lipid, cationic lipid, neutral lipid, charged lipid, steroid, polymer conjugated lipid, stabilizing lipid, or any combination thereof (Pg. 38). Suitable phospholipids include dioleoylphosphatidylethanolamine (DOPE) (Pg. 39). In some embodiments, the LNP comprises a phospholipid in a concentration range of about 15 mol% to about 50 mol% (Pg. 40). In some embodiments, the LNP comprises a cholesterol lipid in a concentration range of about 0 mol% to about 100 mol% (Pg. 40). In one embodiment, the nucleic acid molecule is a DNA molecule (Pg. 45). In one embodiment, the therapeutic agent is an antigen (Pg. 45). In certain embodiments, the antigen comprises a tumor antigen such as MAGE (satisfies claim 5-6) (Pg. 57). In one embodiment, the cationic lipid is present in the composition in an amount from about 30 to about 70 mole percent (Pg. 63). Suitable stabilizing lipids include pegylated lipids (Pg. 65). They may be included in an amount of 1 to about 10 mole percent (Pg. 66). Cancers to be treated by the methods of treatment include leukemia and melanoma (Pg. 84).
Mitchell differs from the instant claims insofar as not disclosing wherein the lipid nanoparticle comprises double stranded DNA that is at least 45 base pairs in length.
However, Dutreix discloses double-stranded nucleic acid fragments having preferably 8-500 bp which are used to DNA repair induced lethality (DRIL in short) of tumoral cells/tissues (Abstract). The tumor sensitivity to direct or indirect DNA damaging anticancer therapies can be
enhanced by using double stranded nucleic acid molecules (col 2, line 50-53). They can be made linear or made of hairpin double stranded nucleic acids in which the loop can be nucleic acids (satisfies claim 42) (col 3, line 42-43). DRIL molecules can be made of at least one free dsDNA end (col 3, line 47-48). The method for promoting tumor sensibility to anticancer therapies comprises coupling the treatment with DRIL molecules with a double chemotherapy (col 5, line 30-31). In certain embodiments, the DRIL molecules are not chemically modified and correspond to native nucleic acid fragments (col 5, line 41-43).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant claims, to have modified the lipid nanoparticles of Mitchell to comprise the double stranded DNA of Dutreix to use in a method for treating cancer/tumor motivated by the desire to enhance the tumor sensitivity to direct or indirect DNA damaging anticancer therapies as taught by Dutreix.
Alternatively, generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Mitchell discloses wherein the lipid nanoparticle comprises nucleic acids. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the composition of Mitchell to comprise the double stranded DNA of Dutreix as the nucleic acids to use in a method of treating cancer/tumor, since it is a known nucleic acid for use in treating cancers as taught by Dutreix.
Regarding claim 42, as discussed above, Mitchell in view of Dutreix disclose wherein the double stranded nucleic acid molecules can be made of hairpin double stranded nucleic acids in which the loop can be nucleic acids. This satisfies a dsDNA region as instantly claimed.
Regarding claims 45-46, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). As discussed above, the LNP may comprise 15-50 mol% of a phospholipid, 0-100% of cholesterol, 30-70 mol% of a cationic lipid, and 1-10 mol% of pegylated lipid. Accordingly, because the ranges recited in the instant claims overlap with and/or lie inside the ranges disclosed by Mitchell in view of Dutreix, the ranges disclosed by Mitchell in view of Dutreix meet the instantly recited limitations.
Therefore, the combined teachings of Mitchell and Dutreix render obvious claims 4-6, 38-39, 42, and 44-46.
2. Claim(s) 7-9, 12-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al. (WO 2021/077066, Apr. 22, 2021) (hereinafter Mitchell) in view of Dutreix et al. (US 7,595,302, Sep. 29,2009) (hereinafter Dutreix) and further in view of Bexon et al. (WO 2020/168005, Aug. 20, 2020) (hereinafter Bexon).
The teachings of Mitchell and Dutreix are discussed above.
The combined teachings of Mitchell and Dutreix differ from the instant claims insofar as not disclosing wherein the composition comprises administering a cancer therapeutic agent such as a PD-L1 and/or a PD-1 checkpoint inhibitor.
However, Bexon discloses methods of treating cancer using a combination of spherical nucleic acids and a checkpoint inhibitor (Abstract). Tumors use certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. These checkpoint pathways can prevent a latent immune response from acting on the tumor (Pg. 1). Suitable cancers to be treated include melanoma and leukemia (Pg. 4). In some embodiments, the checkpoint inhibitor is a PD-1 antibody or a PD-L1 antibody. In some embodiments, the checkpoint inhibitor is pembrolizumab or cemiplimab (Pg. 6). In some embodiments, the cancer in the subject is refractory or resistant to treatment with a checkpoint inhibitor (Pg. 6). The administration of the spherical nucleic acid in combination with the checkpoint inhibitor results in one or more of increased cytokine expression, increased chemokine expression, or increased immune cell activation (Pg. 8). Suitable subjects include humans (Pg. 40).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified the method/LNP of Mitchell in view of Dutreix to further comprise administering a cancer therapeutic agent such as a PD-L1 and/or a PD-1 checkpoint inhibitor motivated by the desire to achieve one or more of increased cytokine expression, increased chemokine expression, or increased immune cell activation as taught by Bexon. One of ordinary skill in the art would have had a reasonable expectation of success since Mitchell in view of Dutreix disclose wherein the LNP delivers therapeutic agents and wherein the double stranded DNA maybe combined with chemotherapeutics.
Regarding claim 9, as discussed above, in some embodiments, the checkpoint inhibitor is pembrolizumab or cemiplimab. This satisfies the instantly recited limitations.
Regarding claims 13-14 and 17-19, as discussed above, in some embodiments, the cancer in the subject is refractory or resistant to treatment with a checkpoint inhibitor. This satisfies the instantly recited limitations.
Therefore, the combined teachings of Mitchell, Dutreix, and Bexon render obvious claims 7-9, 12-15, and 17-20.
3. Claim(s) 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al. (WO 2021/077066, Apr. 22, 2021) (hereinafter Mitchell) in view of Dutreix et al. (US 7,595,302, Sep. 29,2009) (hereinafter Dutreix) and further in view of Siders et al. (Molecular Therapy, Vol. 6, No. 4, October 2002) (hereinafter Siders).
The teachings of Mitchell and Dutreix are discussed above.
The combined teachings of Mitchell and Dutreix differ from the instant claim insofar as explicitly not disclosing wherein the DNA used is noncoding.
However, Siders discloses that treatment of established peritoneal mesothelial tumors
with complexes composed of cationic lipid and noncoding plasmid DNA (pNull) results in the
inhibition of tumor growth accompanied by the induction of a tumor-specific cellular immune response. Among the tumors treated were melanoma tumors (Abstract).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified the method/LNP of Mitchell in view of Dutreix to further comprise administering a noncoding DNA motivated by the desire to inhibit tumor growth and induce tumor-specific cellular immune response as taught by Siders. One of ordinary skill in the art would have had a reasonable expectation of success since Mitchell in view of Dutreix disclose wherein the LNP comprises a cationic lipid.
Therefore, the combined teachings of Mitchell, Dutreix, and Siders render obvious claim 43.
4. Claim(s) 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell et al. (WO 2021/077066, Apr. 22, 2021) (hereinafter Mitchell) in view of Dutreix et al. (US 7,595,302, Sep. 29,2009) (hereinafter Dutreix) and further in view of Navarro et al. (WO 2021/123332, Jun. 24, 2021) (hereinafter Navarro) as evidenced by ChemSrc (DMG-PEG2000(C14-PEG2000), Dec. 18, 2020) (hereinafter ChemSrc).
The teachings of Mitchell and Dutreix are discussed above.
The combined teachings of Mitchell and Dutreix differ from the instant claim insofar as explicitly not disclosing wherein the composition comprises cKK-E12 and C14-PEG2000.
However, Navarro discloses lipid nanoparticles for the delivery of nucleic acids (Abstract). In further aspects, the invention provides the use of the compositions incorporating a cationic lipid and a nucleic acid compound as medicines (Pg. 4). Suitable cationic lipids include ckk-E12 (Pg. 54). In some embodiments, the LNPs comprise a polymer conjugated lipid where, preferably, the polymer conjugated lipid is a pegylated lipid (Pg. 55). In a preferred embodiment, the polymer conjugated lipid is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000 (DMG-PEG 2000) (Pg. 57). Diseases which preferably can be treated with the composition include cancer or tumor diseases (Pg. 86).
As evidenced by ChemSrc, DMG-PEG 2000 is C14-PEG2000 (Pg. 1).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. As discussed above, Mitchell in view of Dutreix discloses wherein the composition comprises cationic lipids and pegylated lipids. Accordingly, it would have been prima facie obvious for one of ordinary skill in the art to have formulated the composition of Mitchell in view of Dutreix to comprise ckk-E12 as the cationic lipid and DMG-PEG 2000 as the pegylated lipid to use in a method for treating cancer/tumor, since they are known cationic and pegylated lipids, respectively, as taught by Navarro.
Regarding the components and amounts recited in instant claim 48, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). As discussed above, suitable phospholipids comprise DOPE and the LNP of Mitchell in view of Dutreix and Navarro may comprise 15-50 mol% of a phospholipid, 0-100% of cholesterol, 30-70 mol% of a cationic lipid, and 1-10 mol% of pegylated lipid. Accordingly, because the ranges recited in the instant claims overlap with and/or lie inside the ranges disclosed by Mitchell in view of Dutreix and Navarro, the ranges disclosed by Mitchell in view of Dutreix and Navarro meet the instantly recited limitations.
Therefore, the combined teachings of Mitchell, Dutreix, and Navarro, as evidenced by ChemSrc, render obvious claim 48.
Conclusion
Claims 4-9, 12-15, 17-20, 37-39, 42-46, and 48 are rejected.
Claims 1-3, 22, 36, 49-50, 52, and 56-57 are withdrawn.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
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, Sahana S. Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.A./Examiner, Art Unit 1612
/LEZAH ROBERTS/Primary Examiner, Art Unit 1612
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