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 1-9 are pending. Claims 1-6 are withdrawn. Claims 7-9 are under examination.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 7-9) in the reply filed on 06/04/2026 is acknowledged.
Claims 1-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/04/2026.
Information Disclosure Statement
The information disclosure statements filed 04/25/2024 have been considered and initialed copies are enclosed.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete because it is missing the size of the XML file in bytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claims 7-9 are objected to because of the following informalities:
Please include the full meaning of NRG1 and NRG2.
Claims 7-8 are dependent on non-elected invention that are not under examination. Claim 7 and 8 should be amended to independent form.
Appropriate correction is required.
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.
Claim 7-9 is 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.
Claims 7 and 8 depend on claim 1 which recites “a composition comprising extracellular vesicles (EVs) produced from donor cells engineered to express NRG1, NRG2, or a combination thereof”. The metes and bounds of “donor cells engineered to express NRG1, NRG2, or a combination thereof” is vague and indefinite. It is not clear as written how Applicants intend the donor cells to be engineered to express NRG1, NRG2, or a combination thereof.
Claim 9 is drawn to a method for treating neurofibromatosis type 1 (NF1) in a subject, comprising delivering intracellularly into skin cells of the subject a polynucleotide comprising nucleic acid sequences encoding NRG1, NRG2, or a combination thereof, and a nucleic acid sequence encoding neurofibromin, wherein the skin cells produce EVs decorated with NRG1, NRG2, or a combination thereof and encapsulating neurofibromin as a therapeutic cargo.
The metes and bounds of claim 9 is vague and indefinite because while the skin cells produce EVs decorated with NRG1, NRG2, or a combination thereof and encapsulating neurofibromin as a therapeutic cargo, the claim does not indicate that the polynucleotide comprising nucleic acid sequences encoding NRG1, NRG2, or a combination thereof, and a nucleic acid sequence encoding neurofibromin is expressed. The “term” polynucleotide is not defined in the specification to encompass an expression vector. Thus, in the absence of sequences that enable the expression of the polynucleotide, “delivering intracellularly into skin cells of the subject a polynucleotide comprising nucleic acid sequences encoding NRG1, NRG2, or a combination thereof, and a nucleic acid sequence encoding neurofibromin” is gene therapy and would not result in “skin cells produce EVs decorated with NRG1, NRG2, or a combination thereof and encapsulating neurofibromin as a therapeutic cargo” as claimed.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Verma et al. WO 2021/184022 09/16/2021.
Verma et al disclose a method for selectively delivering a therapeutic cargo to Schwann cells in a subject (paragraph 35, 37, 39), comprising administering to the subject an effective amount of a composition comprising extracellular vesicles (EVs) produced from donor cells (derived from living or dead organism, explanted tissues or organs, prokaryotic or eukaryotic cells, and/or cultured cells -paragraph 100) engineered to express a growth factor such as NRG1 or NRG2 thereof wherein the EVs encapsulate a therapeutic cargo (biologically active molecule -paragraph 39, payload-paragraph 100, payload is growth factor such as NRG1 or NRG2).
Claim(s) 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burzyn et al. WO 2021/030776 02-18-2021 (hereinafter, "Burzyn") cited in IDS.
Burzyn teaches a polynucleotide comprising nucleic acid sequences encoding NRG1, wherein the skin cells produce (extracellular vesicles) EVs decorated with NRG1, NRG2, or a combination thereof (engineered EVs, e.g., exosomes, can be produced from a cell transformed with an exogenous sequence, Para. [0494]; the extracellular vesicle further comprises an exogenous targeting moiety, Para, [0016]; the target moiety is a "tropism moiety". As used herein, the term "tropism moiety" refers to a targeting moiety that when expressed on an EV (e.g., exosome) alters and/or enhances the natural movement of the EV. For example, in some aspects, a tropism moiety can promote the EV (e.g., exosome) to be taken up by a particular cell, Para. [0546]; the target moiety comprises a neurotrophin selected from the group consisting of neuregulin, Para. [0585]; the producer cell is a mammalian cell line. Non-limiting examples of mammalian cell lines include BJ human foreskin fibroblast cells, Para. [0639]).
Burzyn et al discloses a method for selectively delivering the EVs decorated with NRG1, NRG2, or a combination thereof to Schwann cells in a subject, comprising administering to the subject an effective amount of said EVs (a method of treating a cancer in a subject in need thereof, comprising administering an effective amount of an extracellular vesicle disclosed herein, Para, [0039]; EV, e.g., exosomes, disclosed herein can be surface engineered to direct them to a specific cellular type, e.g., Schwann cells, Para. [0545]).
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 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.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Verma et al. WO 2021/184022 09/16/2021 in view of Schulz et al WO 2017182500 10-26-2017 cited IDS.
Verma et al disclose a method of treating cancer such as neurofibromatosis (paragraph 211) in a subject, comprising administering to the subject an effective amount of a composition comprising extracellular vesicles (EVs) produced from donor cells (derived from living or dead organism, explanted tissues or organs, prokaryotic or eukaryotic cells, and/or cultured cells -paragraph 100) engineered to express a growth factor such as NRG1 or NRG2 wherein the EVs encapsulate a therapeutic cargo (biologically active molecule -paragraph 39, payload-paragraph 100, payload is growth factor such as NRG1 or NRG2). Verma et al disclose the use of the exosomes for targeted delivery NRG1 or NRG2.
Verma et al does not disclose treating neurofibromatosis type 1 (NF1).
Schulz et al disclose a method of treating neurofibromatosis type 1 (NF1) comprising administering neuregulin. Schulz et al disclose neuregulin administration represents an effective therapeutic approach for treating neurofibromatosis. Schulz et al disclose that neuregulin family comprise NRG1, NRG2, NRG3, and NRG4 which comprise EGF-like domains that may be used in treating neurofibromatosis type 1 (NF1). See p. 1 lines 5-21, p. 2 lines 1-21, p. 4 lines 3-6, claim 1 and claim 9 on page 39.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have used the composition of Verma et al to treat neurofibromatosis type 1 (NF1) as taught by Schulz et al, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Schulz et al teach that neuregulins including the NRG1, NRG2 can be used to treat neurofibromatosis type 1 (NF1). In addition, the use of the exosomes to deliver NRG1 or NRG2 or combination thereof for treatment of NF1 ensures targeted delivery.
Status of Claims
Claims 1-6 are withdrawn. Claims 7-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLUWATOSIN A OGUNBIYI whose telephone number is (571)272-9939. The examiner can normally be reached IFP.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645
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