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 .
Claim Status
Claims 1-9, 13, 24, 28, 31-35, 37 and 55-56 are pending.
Claims 3-7, 9, 13, 24, 31-34 and 37 are currently amended.
Claims 10-12, 14-23, 25-27, 36 and 38-54 have been canceled.
Claims 2-3, 8-9, 28, 31-35, 37 and 56 are withdrawn as these claims are drawn to a non-elected group.
Claim 56 has been added.
Claims 1, 4-7, 13, 24 and 55 are currently under consideration.
Claims 1, 4-7, 13, 24 and 55 are rejected.
Acknowledgement of Receipt
Applicants’ election without traverse of Group II., claims 1, 4-7, 13, 24 and 55 drawn to a method of treating a proliferative disease in the reply filed on 10/03/2025 is acknowledged. Applicants’ election without traverse of SEQ ID NO. 1 (claim 1); covalently attached (claim 7) in the reply filed on 10/03/2025 is acknowledged. Claim 8 (i.e., non-covalently) and claim 9 (i.e., indirectly associated) are drawn to a non-elected species and have been withdrawn. This Office Action is in response to Applicants’ elections filed 10/03/2025.
Priority
This application is a 371 of PCT/US2021/062888 filed 12/10/2021. PCT/US2021/062888 has PRO 63/124,827 filed 12/13/2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 09/25/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this IDS has been considered by the Examiner.
Claim Objections
Claim 55 is objected to because of the following informalities: the number two in parentheses, “(2)” recited in line 9 of claim 55 lacks a component with which it is associated or is to appear after (e.g., (1)). Appropriate correction is 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.
Claims 1, 4-7, 13, 24 and 55 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 a method of treatment using psilocybin associated with a targeting peptide when administering to the subject orally, does not reasonably provide enablement for non-oral methods of treatment. 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.
In Geiger et al. (DARK Classics in Chemical Neuroscience: Psilocybin. ACS Chem. Neurosci. 2018, 9, 2438−2447) psilocybin undergoes hepatic first-pass metabolism where it is dephosphorylated to the active form of psilocybin (pg. 2440, sec. III. Drug Metabolism). In this case, the specification does not provide enablement for any claims in which the liver is avoided. Even if during non-oral administrations (e.g., intravenously), some of the recited “therapeutically effective amount of a pharmaceutical composition” did reach the liver where it would be metabolized to the active psilocybin, the specification remains to be deficient in evidence to show that the claimed invention would be capable of delivering the psilocybin “to a target environment of the subject” or even capable of crossing the blood brain barrier. Upon a thorough search of Applicants’ specification, it appears that no exemplary embodiments are provided. Applicants disclose only a section entitled “Experimental Plan” with no results (see Spec., [0119], Experiments 1, 2). MPEP 2164.06(b)(I.)(A) states that wherein the teachings set forth in the specification provided no more than a "plan" or "invitation" for those of skill in the art to experiment, the instant disclosure was non-enabling.
Claims 1, 4-7, 13, 24 and 55 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 a method to treat a proliferative disease, that being cancer, the specification does not reasonably provide enablement for a method to treat all proliferative diseases, including all cancers. 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 specification only discloses cancer, types thereof, and solid tumors as the proliferative disease (see Spec., [0008]). There is no mention of any other proliferative diseases. In Sporn MB, Harris ED Jr. (Proliferative diseases. Am J Med. 1981 Jun;70(6):1231-5), non-cancerous proliferative diseases include those that are cardiovascular, e.g., atherosclerosis, in which smooth muscle cells and plaque buildup in artery walls; skin conditions, e.g., psoriasis that has visible symptoms of scaly patches that can spread; autoimmune/inflammatory, e.g., rheumatoid arthritis (RA); and liver disease, e.g., cirrhosis where there is an excessive matrix turnover and scarring in the liver (abstract).
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 (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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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. Applicants are 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, 4-7, 13, 24 and 55 are rejected under 35 U.S.C. § 103 as being unpatentable over Londesbrough (US 2023/0023092, filed 04/17/2020, equivalent WO 2020/212948 cited on IDS) and Moudgil (US 2019/0359651, pub. 11/28/2019, equivalent WO 2018/132467 cited on IDS), further evidenced by Tyagi et al. (Surgical Neurology International 2016, 7:78).
For the purposes of this office action, the Applicant is made aware that these 103 rejections are being made to the embodiments to the claims that may be enabled.
Londesbrough discloses a method comprising administering an effective amount of crystalline psilocybin to the subject (title, abstract, claim 1). The methods described may be used to treat a variety of diseases, disorders, and while Londesbrough focuses on the benefits of psilocybin in neural plasticity and cognitive function, the disclosure teaches that such benefits extend to subjects that have cancer ([0014], [0112], [0133], [0344], [0554]). Londesbrough provides a pharmaceutical formulation comprising high purity crystalline psilocybin and one or more pharmaceutically acceptable carriers of excipients ([0172], [0214]). Londesbrough provides pharmaceutical compositions a formulation comprising crystalline psilocybin and one or more pharmaceutically acceptable carriers or excipients ([0213], [0225] see table, capsule, dry powder, solution; [0691] Examples formulation development where psilocybin is at 1.0 % w/w).
Londesbrough does not teach that the pharmaceutical composition comprises a targeting peptide comprising an amino acid sequence of SEQ ID NO: 1 wherein the targeting peptide is capable of delivering the psilocybin.
Moudgil discloses a method of detecting neuroinflammation in a subject, comprising administering to the subject a central nervous system homing peptide (title, abstract, [0054], claim 48). Moudgil discloses a molecular approach to identify novel markers in inflamed CNS ([0047]). Specifically regarding SEQ ID NO 1, Applicants disclose SEQ ID NO: 1 as having the amino acid sequence KRSS (see Spec., [0042], Table 1). Moudgil provides an isolated central nervous system-homing peptide, wherein the peptide comprises an amino acid motif selected from the group consisting of (SEQ ID NO: 1) KRSS ([0011], pg. 12, sequence listing: Lys Arg Ser Ser) and provides embodiments thereof ([0058]).
Moudgil teaches peptide, amino acid, and linker bond; ends or side chains(s) of homing peptide are joined to a scaffold that provides a molecular and either end (C or N-terminus) of a homing peptide can be coupled to the scaffold ([0057]). Compositions comprising the CNS-homing peptide and therapeutically active agent may be used to treat a variety of conditions associated with inflammation of the CNS ([0055]). The targeting peptide can be linked to a therapeutic agent, which may be used to treat neuroinflammation, serve as a “molecular homing device” to release the agent via reversible reductive cleavage of a disulfide bond ([0066-0070]). Moudgil teaches homing peptides distributed in the CNS conjugated with imaging agents which target inflamed CNS, and as the homing peptide target inflamed CNS, such conjugates can serve as good indicators of disease activity, specifically areas of inflammation ([0073]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to utilize the targeting peptide of Moudgil to deliver the psilocybin i.e., therapeutic agent, taught by Londesbrough with enhanced targeting. One would be motivated to do so with a reasonable expectation of success because Moudgil provides results that show that peptide KRSS preferentially homed to inflamed spinal cord of EAE mice but not in normal mice, and by extrapolation, in patients with neuroinflammatory conditions of the CNS ([0126]). Furthermore, Moudgil discloses the CNS-homing peptide is capable of application in a kit that includes a pharmaceutical composition ([0098]). Improves upon Londesbrough wherein subjects having chronic inflammatory demyelinating polyneuritis (Londesbrough [0025], [0361], [0447]). In addition, Moudgil teaches that neuroinflammation is associated with conditions to include traumatic brain injury (TBI) ([0055], [0094]). Evidenced by Tyagi et al., post-traumatic inflammation in the brain is linked to oncogenic transformation and glioma initiation and glioblastoma (i.e., brain cancer) (see Introduction).
Regarding claim 4, Londesbrough teaches that in some embodiments, the additional comorbidity or disorder is cancer ([0014], [0112], [0133], [0344], [0554]).
Regarding claim 5, Londesbrough meets the requirement that the target environment is the nervous system by disclosing a method of treating a subject in need thereof, the method comprising administering to the subject a therapeutically effective dose of psilocybin, wherein the subject has a demyelinating disease of the central nervous system ([0025], [0334], [0336], [0361], [0447] see embodiment 11).
Regarding claim 6 (i.e., directly) and claim 7 (i.e., covalently), Moudgil provides a homing peptide conjugate, i.e., a homing peptide having an amino acid sequence as described herein linked to one or more moieties (i.e., a physical, chemical, or biological material linked to a peptide) ([0067]). Drug molecules, prodrug molecules, or other therapeutic agents may be linked to a homing peptide via covalent bonds or non-covalent bonds ([0068]). The covalent linking of homing peptides to other components including therapeutic agents can be accomplished using techniques which would be readily apparent to one of ordinary skill in the art, e.g., homing peptides can be linked to molecules via the use of well-known coupling or activation agents ([0079-0080]). While Moudgil discloses a CNS-homing peptide comprising identical amino acid (SEQ ID NOs: 1) associated with an anti-inflammatory agent, Moudgil does not explicitly disclose that the anti-inflammatory agent is psilocybin.
In terms of a targeting peptide comprising SEQ ID NO 1 covalently attached to psilocybin, it would have been prima facie obvious, before the effective filing date of the claimed invention, to use the combined teachings of the references to arrive at the claimed invention. The CNS homing peptides taught by Moudgil mirror those in the instant claims. Moudgil teaches CNS-homing peptides combined with therapeutically active agent used to treat a variety of conditions associated with inflammation of the CNS. Moudgil discloses a therapeutic agent associated with the CNS-homing peptide. While Moudgil does not specifically disclose psilocybin as the active agent, Londesbrough teaches that psilocybin is used for treating subjects with neuroinflammatory conditions, and as a therapeutic to treat depressive disorders due to a medical condition (e.g., cancer). Therefore, one of ordinary skill in the art would anticipate success in substituting the generic anti-inflammatory disclosed by Moudgil with psilocybin, which is taught by Londesbrough as a therapeutic to treat depression because of its ability to reduce neuroinflammation (Londesbrough [0650]). A simple substitution of one known equivalent element for another obtains predictable results and a person of ordinary skill has good reason to pursue the known options within their technical grasp. If this leads to the anticipated success, it is likely the product not of innovation, but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)).
Regarding claim 13, Londesbrough teaches, at least one dose of psilocybin is administered to the subject, each dose of psilocybin administered to the subject is a therapeutically effective dose, and the dose of psilocybin is in the range of about 0.1 mg to about 100 mg ([0033], [0230-0248], [0251], claims 60-63). MPEP 2144.05 states that a prima facie case of obviousness exists in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art.
Regarding claim 24, pharmaceutical composition orally, Londesbrough discloses that in some embodiments the psilocybin is administered in an oral dosage form ([0032]).
Regarding claim 55, Londesbrough discloses methods to treat depressive disorder due to a medical condition to include certain cancers (e.g., pancreatic) ([0112]). While Londesbrough does not teach a solid tumor, in light of these teachings, it would have been prima facie obvious to a person of ordinary skill in the art, that proliferative disease encompasses solid tumor(s). For example, in the case of pancreatic cancer suggested by Londesbrough is a type of solid tumor cancer forming a firm mass that can grow and invade surrounding tissues. And, as mentioned above, Moudgil associates neuroinflammation with TBI ([0055], [0094]) and evidence from Tyagi et al., shows how post-traumatic inflammation in the brain is linked to oncogenic transformation and glioma initiation and glioblastoma (see Introduction).
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.
Co-pending application no. 18/004,546
Claims 1, 4-7, 13, 24 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, and 37 of copending Application No. 18/004,546 (reference application '546).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are each directed to overlapping embodiments: a method of treating a disease in a subject by administering a CNS-homing peptide associated with psilocybin and a pharmaceutical composition comprising the same. Furthermore, the sequences of ‘546, represented by SEQ ID NOs: 1-22, are identical to those which are instantly claimed by SEQ ID NOs: 1-22. Therefore, '546 teaches an identical method and composition as what is instantly claimed and instant claims 1, 4-7, 13, 24 and 55 are anticipated by '546 claims 1, 10, and 37. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending application no. 18/004,400
Claims 1, 4-7, 13, 24 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 13, and 32-33 of copending Application No. 18/004,400 (reference application '400).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are each directed to overlapping embodiments: a method of treating a disease in a subject by administering a CNS-homing peptide associated with psilocybin and a pharmaceutical composition comprising the same. Furthermore, the sequences of '400, represented by SEQ ID NOs: 1-22, are identical to those which are instantly claimed by SEQ ID NOs: 1-22. Therefore, '400 teaches an identical method and composition as what is instantly claimed and instant claims 1, 4-7, 13, 24 and 55 are anticipated by '400 claims 1-3, 13, and 32-33. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 4-7, 13, 24 and 55 are rejected; no claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 900-500 ET.
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/Karen Ketcham/
Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614