DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 7-17-23.
Claims 25-27, 112-119, 131-136 are pending in the instant application.
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.
Claims 113-119, 131, 132 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 113, in line 3, recites the phrase “RNAi agent at least substantially complementary to the target gene.” This phrase is vague and indefinite.
Appropriate correction is required.
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 113-119, 131-132 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the targeting and inhibition of myostatin (MSTN) in the triceps and gastrocnemius of mice, rats and monkeys upon the administration by unknown means, and dosing regimens of RNAi in various lipid formulations and further comprising lipid PK/PD modulators, does not reasonably enable methods of reducing any target gene in any target cell in vivo, or treating, preventing or ameliorating any condition, disease or disorder comprising administration by any route of compositions comprising any RNAi agent at least substantially complementary to any target gene and the lipid formulations claimed.
. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The claims are drawn to methods of reducing any target gene in any target cell in vivo, or treating, preventing or ameliorating any condition, disease or disorder comprising administration by any route of compositions comprising any RNAi agent at least substantially complementary to any target gene and the lipid formulations claimed.
Teachings in the art and in the specification.
Teachings in the art:
Roberts et al (Nature Rev., Drug Discovery, Vol. 19, pages 673-694 (2020)) teaches on page 673 that “achieving efficient oligonucleotide delivery, particularly to extrahepatic tissues, remains a major translational limitation.”
Kobelt et al (Cancer Gene Therapy in Gene Therapy of Cancer: Methods and Protocols, Methods in Molecular Biology, Vol. 2521, pages 1-15 (Springer Nature 2022)) teach that limitations to cancer gene therapy relate to limitations in gene transfer efficiency (see esp. pages 3-4).
In addition, Osborn et al (Nucleic Acid Therapeutics, Vol. 28, No. 3, pages 128-136 (2018)) state the following about challenges to siRNA delivery on page 128:
…The primary challenge facing the clinical development of small interfering RNAs (siRNA) has been overcoming barriers that impede in vivo delivery. siRNAs are large, polyanionic macromolecules with intrinsically poor pharmacological properties. Unmodified siRNAs have a half-life of less than 5 min in circulation, and they do not permeate intact cellular membranes…
Damase et al (Frontiers in Bioengineering and Biotechnology, Vol. 9, Article 628137, pages 1-24 (2021)) on page 13 also address the challenges of using RNA-based drugs:
Targeted delivery is a major hurdle for effective RNA therapeutics, a hurdle that must be overcome to broaden the application of clinical translation of this type of therapeutic. …There is a need for novel delivery vehicles that will deliver the RNA drug to the site of therapeutic action facilitating the entry of the RNA drug into the cytoplasm where it may exert its effect…
Bost et al (ACS Nano, Vol. 15, pages 13993-14021 (2021)) on page 13993 also address the current challenges of oligonucleotide therapeutics:
…Historically, the largest hindrance to the widespread usage of ON therapeutics has been their inability to effectively internalize into cells and escape from endosomes to reach their molecular targets in the cytosol or nucleus…
The Teachings in the Specification:
The specification teaches at ¶¶ 0706-0782 the administration of pharmaceutical compositions comprising various dosing regimens comprising formulations of lipids, lipid PK/PD formulations, peptide delivery agents and RNAi specifically targeting MSTN mRNA. It is unclear, however, what route of administration was used in these experiments in mice, rats and monkeys. The inhibition of the MSTN target gene was measured in the triceps and gastrocnemius.
The examples provided in the instant specification, of the inhibition of MSTN in the triceps and gastrocnemius by undisclosed routes of administration, are not representative or correlative of the ability to provide in vivo effects comprising the administration by any route of the therapeutic compositions claimed.
In light of the teachings in the art and the specification, one skilled in the art would not accept on its face the examples provided in the instant disclosure, and summarized above, as being correlative or representative of the ability to provide therapeutic effects in any subject comprising any route of administration, as instantly claimed.
Since the specification fails to provide the requisite guidance for delivery via any route of administration and provision of therapeutic effects in a subject, and since determination of the factors required for accomplishing therapeutic efficacy in a subject is highly unpredictable, it would require undue experimentation to practice the invention over the broad scope claimed.
For the aforementioned reasons, the instant rejection under 35 U.S.C. 112, first paragraph is proper.
Claims 113-119, 131-132 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The breadth of the claims:
The claims are drawn to methods of reducing any target gene in any target cell in vivo, or treating, preventing or ameliorating any condition, disease or disorder comprising administration by any route of compositions comprising any RNAi agent at least substantially complementary to any target gene and the lipid formulations claimed
Teachings in the specification:
This phrase is recited in ¶¶ 0063, 0232, 0233 and 0318 and the specification suggests that 85% complementary is within the definition of “at least substantially complementary.”
No examples have been provided for at least substantially complementary. The specification, prior art and claims do not adequately describe the genus of RNAi agents claimed, and/or fail to provide a representative number of species, and do not indicate what distinguishing attributes are concisely shared by the members of this genus, and further whereby therapeutic effects have been provided in any subject.
For the reasons stated above, the instant rejection for lacking adequate written description is proper.
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 25-27, 112 and 133, 135, 136 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-10 of U.S. Patent No. 11,845,937. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compositions comprising LP 29a and LP 29b.
Claims 25-27, 112 and 133, 135, 136 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20, 31 and 57 of copending Application No. 18/181,311 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compositions comprising LP 29a and LP 29b.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
LP 238b appears free of the prior art searched and of record.
Claim 134 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.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
1-20-26
/JANE J ZARA/Primary Examiner, Art Unit 1637