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 .
Election/Restrictions
Applicant’s election of (i) 1st scaffold PTGFRN protein, (ii) 2nd scaffold BASP protein, and (iii) non-peptide linker in the reply filed on 4/8/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
Claims 1, 66-69, 78-87 are pending.
Claims 2-65, 70-77, and 88-122 are cancelled.
Claims 79 and 85-86 are withdrawn as being directed to a non-elected invention, the election having been made on 4/8/2026.
Claims 1, 66-69, 78, 80-84, and 87 have been examined.
Priority
This application is a 371 of PCT/US2021/022420 03/15/2021
PCT/US2021/022420 has PRO 63/059,103 07/30/2020
PCT/US2021/022420 has PRO 63/055,657 07/23/2020
PCT/US2021/022420 has PRO 63/050,651 07/10/2020
PCT/US2021/022420 has PRO 63/035,367 06/05/2020
PCT/US2021/022420 has PRO 63/016,213 04/27/2020
PCT/US2021/022420 has PRO 63/010,603 04/15/2020
PCT/US2021/022420 has PRO 62/989,491 03/13/2020
Information Disclosure Statement
No IDS of record.
Claim Objections
Claims 81 and 84 are objected to because of the following informalities:
Claim 81 contains the acronym “PTGFRN”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Prostaglandin F2 Receptor Negative Regulator” with the acronym indicated in parentheses as (PTGFRN). The abbreviations can be used thereafter.
Claim 84 contains the acronym “BASP1”, and an acronym in the first instance of claims should be expanded upon/spelled out as “Brain Abundant Membrane Attached Signal Protein 1” with the acronym indicated in parentheses as (BASP1). The abbreviations can be used thereafter.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 66-67, and 78 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alvarez-Erviti et al. (Nature Biotechnology. 2011; 29: 341–345, previously cited 2/13/2026).
Claim 1 is drawn to a method of treating a neurological disorder in a subject in need thereof, comprising administering to the subject a cell-targeting extracellular vesicle (EV) comprising an antigen.
PNG
media_image1.png
336
402
media_image1.png
Greyscale
Alvarez-Erviti et al. teach “Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes” (Title). Alvarez-Erviti et al. teach the delivered siRNA effective to knockdown 60% mRNA and 62% protein of a therapeutic target in Alzheimer’s disease (Abstract). Alvarez-Erviti et al. teach in vivo delivery siRNA via tail vein injection (p346, col 2, para 4). Alvarez-Erviti et al. show a targeting peptide of central nervous system–specific rabies viral glycoprotein (RVG) peptide (YTIWMPENPRPGTPCDIFTNS-RGKRASNG) that specifically binds to the acetylcholine receptor is fusion to the extra-exosomal N-terminus of murine Lamp2b protein in the exosomes, secreted extracellular vesicles, (p341, col 2, para 2) as shown follows (p342, Fig 1). The rabies viral glycoprotein (RVG) peptide reads on an antigen. In addition, the exosomes isolated from producing cells also comprise cellular proteins further reading on antigens, reading on claim 1.
With respect to claims 66-67, Alvarez-Erviti et al. teach the targeting peptide fusion, covalently linked, to the extra-exosomal N terminus of murine Lamp2b, a protein found abundantly in exosomal membranes (p341, col 2, para 2), reading on a first scaffold moiety of Lamp2b.
With respect to claim 68, Alvarez-Erviti et al. show the exosomes expressing the targeting moiety conjugated Lamp2b secreted by the producing cells further inherently comprising other cellular membrane proteins and membrane phospholipids (p342, Fig 1), reading on a second scaffold protein as a producing-cell membrane scaffold protein.
With respect to claim 78, the targeting peptide fusion, covalently linked, to the extra-exosomal N terminus of murine Lamp2b via an amide bond, reading on the antigen linked to the 1st scaffold protein by a linker of an amide bond (p342, Fig 1).
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.
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.
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.
1. Claims 1, 66-69, 78, 80-83, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Dooley et al. (US 10,195,290 B1) in view of Alvarez-Erviti et al. and Kooijmans et al. (Pharmacological Research 111 (2016) 487-500).
Claim 1 is drawn to a method of treating a neurological disorder in a subject in need thereof, comprising administering to the subject a cell-targeting extracellular vesicle (EV) comprising an antigen.
Dooley et al. teach methods of preparing a therapeutic exosome using surface-engineered
PNG
media_image2.png
376
326
media_image2.png
Greyscale
exosomes with high density of exosome proteins for affinity purification, localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins (Abstract). Dooley et al. teach exosome as the term "extracellular vesicle" or "EV" refers to a cell-derived vesicle comprising a membrane that encloses an internal space (col 10, line 15-23). Dooley et al. teach fusion of an affinity tag to an exosome protein for purification of surface-engineered exosomes (col 6, line 66-67 to col 7, line 1-3; col 16, line 11-17) and further show the use of an antibody for specific isolation of PTGFRN surface-engineered exosomes (col 41, Sec. 6.9.7; col 43, Sec 6.9.11 as shown in Fig 26 above. Dooley et al. teach a targeting moiety can also be fused to an exosome protein for targeting the exosome to a specific organ, tissue, or cell for a treatment using the exosome (col 16, line 48-55). Dooley et al. further show a therapeutic polypeptide can be conjugated to an exosome protein of PTGFRN (col 44, line 1-5; Fig 36). Dooley et al. teach an exosome protein (e.g., PTGFRN of Dooley’s SEQ ID NO: 1 with 100% identity to the instant SEQ ID NO: 1) can be a native full-length protein or a fragment or modified PTGFRN protein (e.g., Dooley’s SEQ ID NO: 3 with 100% identity to the instant SEQ ID NO: 3 and Dooley’s SEQ ID NO: 33 with 100% identity to the instant SEQ ID NO: 33). Dooley et al. further teach exosome proteins provided herein contain modified proteins more highly enriched on their surface (col 17, line 3-13) than exosomes produced using conventional exosome scaffold protein of lysosome-associated membrane protein 2 of LAMP2 and LAMP2B (col 17, line 3-22 and 35-46).
Dooley et al. did not specify a neuron-targeting moiety conjugated to exosome.
Similarly, Alvarez-Erviti et al. teach “Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes” (Title). Alvarez-Erviti et al. show a targeting peptide of central nervous system–specific rabies viral glycoprotein (RVG) peptide (YTIWMPENPRPGTPCDIFT-NSRGKRASNG) that specifically binds to the acetylcholine receptor (p341, col 2, para 2) to deliver the targeted exosomes comprising a therapeutic agent to treat Alzheimer’s disease (Abstract). The RVG targeting peptide reads on both a targeting moiety and antigen.
Because (i) Alvarez-Erviti et al. teach the RVG targeting peptide is specifically binds to the acetylcholine receptor on neuron cells and (ii) Dooley et al. teach a targeting moiety can also be fused to an exosome protein for targeting the exosome to a specific organ, tissue, or cell for a treatment using the exosome (col 16, line 48-55) and PTGFRN protein is more highly enriched on surface-engineered exosomes (col 17, line 3-13) than exosomes produced using conventional exosome scaffold protein of Alvarez-Erviti’s lysosome-associated membrane protein 2 of LAMP2 and LAMP2B (col 17, line 3-22 and 35-46), one of ordinary skill in the art would have found it obvious to beneficial fuse Alvarez-Erviti’s RVG targeting peptide (antigen) to Dooley’s higher density of PTGFRN protein (e.g., SEQ ID NO: 1, 3, or 33) to generate PTGFRN surface-engineered exosomes targeting to acetylcholine receptor on brain neuron cells to deliver a therapeutic agent for treating a neurological disorder such as Alzheimer’s disease taught by Alvarez-Erviti et al., reading on claim 1.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Dooley’s surface-engineered exosomes with high density of exosome proteins (e.g., PTGFRN) and (ii) Alvarez-Erviti’s acetylcholine receptor binding peptide because (a) Dooley et al. teach a targeting moiety can also be fused to an exosome protein for targeting the exosome to a specific organ, tissue, or cell for a treatment using the exosome (col 16, line 48-55) and (b) Alvarez-Erviti et al. show a targeting peptide of central nervous system–specific rabies viral glycoprotein (RVG) peptide (YTIWMPENPRPGTPCDIFT-NSRGKRASNG) that specifically binds to the acetylcholine receptor (p341, col 2, para 2) to deliver the targeted exosomes comprising a therapeutic agent to treat Alzheimer’s disease (Abstract). The combination would have reasonable expectation of success because both references teach the use of a targeting exosomes to treat a disease.
With respect to claims 66-67, Dooley et al. teach PTGFRN (e.g., a full-length SEQ ID NO: 1) is a robust scaffold that is fusion to a payload of FVIII lacking the B Domain (BDDVIII) on N-, C-, or both the termini (p44, line 33-40).
With respect to claims 68-69, Dooley et al. teach a targeting moiety can be fused to an exosome protein for targeting the exosome to a specific organ, tissue, or cell for a treatment using the exosome (col 16, line 48-55). Dooley et al. show a second scaffold protein is IGSF3,
PNG
media_image3.png
433
467
media_image3.png
Greyscale
IGSF8 or BSG as shown follows (Fig. 8).
With respect to claim 78, Dooley et al. teach the use of a linker for conjugating a therapeutic compound to an exosome protein. Dooley et al. teach a therapeutic compound can be nucleotides, amino acids, lipids, carbohydrates, or small molecules (p16, line 25-27), reading on claim 78. For a therapeutic compound not a polypeptide, it would be obvious to use a linker of a non-polypeptide moiety, reading on claim 80. Kooijmans et al. is further cited to show the use of a chemical linker, such as N-hydroxy succinimidyl ester reactive groups, to a lysine residue known to the level of ordinary skill in the art (p490, col 2, Sec 2.4, para 1).
With respect to claim 81-83 and 87, Dooley et al. teach an exosome protein as a full-length PTGFRN of SEQ ID NO: 1 with 100% identity to the instant SEQ ID NO: 1 or a fragment or modified PTGFRN protein SEQ ID NO: 3 with 100% identity to the instant SEQ ID NO: 3 and SEQ ID NO: 33 with 100% identity to the instant SEQ ID NO: 33.
2. Claims 1, 66-69, 78, 80-84, and 87 are rejected under 35 U.S.C. 103 as being unpatentable over Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. as applied to claims 1, 66-69, 78, 80-83, 87 and further in view of Frey et al. (J Cell Biol. 2000 Jun 26;149(7):1443–1454.), Forsova et al. (The FEBS Journal 283 (2016) 1550–1569), and Martyn et al. (Anaesthesia, 2009, 64 (Suppl. 1), pages 1–9).
Claim 84 is drawn to the exosome further comprising a scaffold protein of BASP1.
Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. teach administration of PTGFRN surface-engineered exosomes targeted to the acetylcholine receptor to treat a neurological disorder.
Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. do not specify the targeting exosomes further comprising a protein of BASP1.
Frey et al. teach “Shared and Unique Roles of CAP23 and GAP43 in Actin Regulation, Neurite Outgrowth, and Anatomical Plasticity” (Title). Frey et al. teach CAP23 protein is a membrane associated protein (p1452, col 1, para 1). Frey et al. teach CAP23 is widely and abundantly expressed during development, maintained in selected brain structures in the adult and reinduced during nerve regeneration. Frey et al. teach a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction can be rescued by CAP23 in adult motoneurons (Abstract) as shown in figure 3 (p1447).
PNG
media_image4.png
602
771
media_image4.png
Greyscale
Forsova et al. is cited to show Brain acid-soluble protein-1 (BASP1) also known as NAP-22 and CAP-23 and abundant at the inner surface of the plasma membrane of axon terminals. Forsova et al. further teach CAP-23 expression is upregulated during neuritogenesis and axonal regeneration (p1551, Introduction, col 1, para 1). Martyn et al. is cited as evidence to show acetylcholine receptor expression at neuromuscular junction (p2, Fig 1). Because (a) Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. teach administration of PTGFRN surface-engineered exosomes targeted to the acetylcholine receptor (e.g., neuromuscular junction taught by Forsova et al.), (b) Frey et al. teach a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction can be rescued by CAP23/BASP1 in adult motoneurons (Abstract; p1447, Fig 3), and (c) Forsova et al. is cited to show Brain acid-soluble protein-1 (BASP1) also known as NAP-22 and CAP-23 and abundant at the inner surface of the plasma membrane of axon terminals (BASP1 is a membrane associated protein). Forsova et al. further teach CAP-23 expression is upregulated during neuritogenesis and axonal regeneration (p1551, Introduction, col 1, para 1), one of ordinary skill in the art would have found it obvious to combine Brain acid-soluble protein-1 (BASP1/CAP23) with the PTGFRN surface-engineered exosomes targeted to the acetylcholine receptor at neuromuscular junction to treat a neurological disorder by promoting neuritogenesis and axonal regeneration suggested by Forsova et al. (p1551, Introduction, col 1, para 1), reading on claim 84.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. with (ii) Frey et al. in view of Forsova et al. and Martyn et al. because (a) Dooley et al. in view of Alvarez-Erviti et al. and Kooijmans et al. teach administration of PTGFRN surface-engineered exosomes targeted to the acetylcholine receptor to treat a neurological disorder, (b) Frey et al. teach a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction can be rescued by CAP23/BASP1 in adult motoneurons (Abstract) as shown in figure 3 (p1447), (c) Forsova et al. is cited to show Brain acid-soluble protein-1 (BASP1) known as CAP-23 and abundant at the inner surface of the plasma membrane of axon terminals. Forsova et al. further teach CAP-23 expression is upregulated during neuritogenesis and axonal regeneration (p1551, Introduction, col 1, para 1), and (d) Martyn et al. is cited as evidence to show acetylcholine receptor expression at neuromuscular junction (p2, Fig 1). The combination would have reasonable expectation of success because (a) the PTGFRN surface-engineered exosomes targeted to the acetylcholine receptor can deliver a therapeutic agent to cells expressing acetylcholine receptor at neuromuscular junction and (b) BASP1/CAP-23 taught by Frey et al. and Forsova et al.is able to rescue/treat a defect to produce stimulus-induced nerve sprouting at the adult neuromuscular junction as taught by Frey et al. (Abstract’ p1447, Fig 3).
Double Patenting
Statutory Double patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 66-69, 78, 80-84, and 87 of copending Application No. PCTUS2122420 (reference application, 3/15/2021).
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
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, 66-69, 78, 80-84, and 87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-5 of U.S. Patent No. 10,195,290 (the ‘290 patent) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘290 patent disclosed a pharmaceutical composition comprising an exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof.
Claim 4 of the ‘290 patent disclosed PTGFRN as the instant SEQ ID NO: 1.
Claim 5 of the ‘290 patent disclosed PTGFRN as the instant SEQ ID NO: 33.
Claims 1 and 4-5 of the ‘290 patent did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof taught by claims 1 and 4-5 of the ‘290 patent to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 1 and 4-5 of the ‘290 patent with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 1 and 4-5 of the ‘290 patent in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
Claims 1, 66-69, 78, 80-84, and 87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,561,740 (the ‘740 patent) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘740 patent disclosed a pharmaceutical composition comprising an exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof.
Claim 2 of the ‘740 patent disclosed PTGFRN protein as SEQ ID NO: 1.
Claim 3 of the ‘740 patent disclosed PTGFRN protein as SEQ ID NO: 33.
Claims 1-3 of the ‘740 patent did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof taught by claims 1-3 of the ‘740 patent to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 1-3 of the ‘740 patent with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 1-3 of the ‘740 patent in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
Claims 1, 66-69, 78, 80-84, and 87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of U.S. Patent No. 11,992,527 (the ‘527 patent) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘527 patent disclosed an isolated extracellular vesicle (EV) comprising (i) an antigen, (ii) scaffold X moiety, and (iii) scaffold Y moiety.
Claim 12 of the ‘527 patent disclosed scaffold X moiety as PTGFRN and scaffold Y moiety as BASP1.
Claims 1 and 12 of the ‘527 patent did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising both PTGFRN and BASP1 to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising both PTGFRN and BASP1 taught by claims 1 and 12 of the ‘527 patent to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 1 and 12 of the ‘527 patent with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 1 and 12 of the ‘527 patent in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
Claims 1, 66-69, 78, 80-84, and 87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,257,313 (the ‘313 patent) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘313 patent disclosed a pharmaceutical composition comprising an exosome comprising a target protein comprising PTGFRN or a fragment thereof and an excipient.
Claim 1 of the ‘313 patent did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof taught by claims 1-3 of the ‘740 patent to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claim 1 of the ‘313 patent with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 1-3 of the ‘740 patent in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 85 and 97 of copending Application No. 17/441,162 (the ‘162 application, 4/13/2026) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 85 of the ‘162 application disclosed an extracellular vesicle comprising a bioactive molecule linked to a scaffold protein.
Claim 97 of the ‘162 application disclosed the scaffold protein as PTGFRN.
Claims 85 and 97 of the ‘162 application did not teach administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising both PTGFRN and BASP1 to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN as taught by claims 85 and 97 of the ‘162 application to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 85 and 97 of the ‘162 application with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 85 and 97 of the ‘162 application in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 23 of copending Application No. 17/441,524 (the ‘524 application, 6/17/2025) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘524 application disclosed an isolated extracellular vesicle (EV) comprising (i) an antigen, (ii) a first scaffold moiety of PTGFRN protein or a fragment thereof.
Claim 23 of the ‘524 application disclosed the EV further comprising a second scaffold protein of brain acid soluble protein 1 (BASPl protein).
Claims 1 and 23 of the ‘524 application did not disclosed the EV further comprising a targeting moiety to deliver a therapeutic agent to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising both PTGFRN and BASP1 to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN as taught by claims 1 and 23 of the ‘524 application to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 1 and 23 of the ‘524 application with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 1 and 23 of the ‘524 application in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/058,193 (the ‘193 application, 6/10/2025) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘193 application disclosed a method of isolating an exosome comprising PTGFRN protein.
Claim 1 of the ‘193 application did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN taught by claim 1 of the ‘193 application to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claim 1 of the ‘193 application with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claim 1 of the ‘193 application in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. PCTUS1848026 (the ‘026 application, 8/24/2018) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 1 of the ‘026 application disclosed a method of isolating an exosome comprising PTGFRN protein.
Claim 1 of the ‘026 application did not disclose administration of the exosome as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising a scaffold protein of PTGFRN or a functional fragment thereof taught by claim 1 of the ‘026 application to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claim 1 of the ‘026 application with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claim 1 of the ‘026 application in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 66-69, 78, 80-84, and 87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. PCTUS2278150 (the ‘150 application, 10/14/201822) in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Claim 2 of the ‘150 application disclosed a method of producing extracellular vesicles (EVs) from producer cells.
Claims 34-36 of the ‘150 application disclosed the EV comprising a scaffold protein of PTGFRN of SEQ ID NO: 1.
Claims 37-38 of the ‘150 application disclosed the EV comprising a scaffold protein of BASP1.
Claims 2 and 34-38 of the ‘150 application did not disclose administration of the exosome comprising PTGFRN and BASP1 as a drug carrier to treat a neurological disorder.
The relevancy of Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach the use of a targeting exosome comprising both PTGFRN and BASP1 to deliver a drug to treat a neurological disorder described above, not repeated here.
Because Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. teach beneficial use of a targeting exosome comprising both PTGFRN and BASP1 taught by claims 2 and 34-38 of the ‘150 application to treat a neurological disorder, one of ordinary skill in the art would have found it obvious to combine claims 2 and 34-38 of the ‘150 application with Dooley et al., in view of Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al.
Thus, claims 2 and 34-38 of the ‘150 application in view of Dooley et al., Alvarez-Erviti et al., Kooijmans et al. and further in view of Frey et al. Forsova et al., and Martyn et al. are obvious to the instant claims 1, 66-69, 78, 80-84, and 87.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIA-HAI LEE whose telephone number is (571)270-1691. The examiner can normally be reached Mon-Fri from 9:00 AM to 6:00 PM.
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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.L/Examiner, Art Unit 1658
25-June-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights