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 Group I, drawn to claims 1, 4-5, 7, 13-14, 18, 23, 45, 87, 89, 91-93, 99 and 221-224, in the reply filed on 11/24/2025 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)).
Applicant’s election of the following species in the reply filed on 11/24/2025 is acknowledged:
Variable 1 - Applicant elects as the transmembrane domain B) a single pass domain such as VSVG as defined in claim 5;
Variable 2 - Applicant elects as the target molecule, CD antigen as defined in claim 14;
Variable 3 - Applicant elects as the targeting moiety, an scFv as defined in claim 18;
Variable 4 - Applicant elects as the intravesicular polypeptide, a STING pathway activator as defined in claim 87, and 91-93; and
Variable 5 - Applicant elects as cargo, a STING pathway activator as defined in claim 222.
Upon reconsideration, the election of species for Variable 5 is withdrawn.
Claims 225-226 are withdrawn from consideration as being drawn to a non-elected invention. Claims 89, 99, and 221 are withdrawn from consideration as being drawn to a non-elected species.
Claims 1, 4-5, 7, 13-14, 18, 23, 45, 87, 91-93, and 222-224 are examined on the merits herein.
Priority
The instant application is a 371 of PCT/CA2020/051630 filed 11/27/2020, which claims benefit of provisional application 62/941,768 filed 11/28/2019.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See Table 12.
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 sequence identifiers, 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.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 14 and 87 are objected to because of the following informalities:
Regarding claim 14: In line 1, “method1” should be corrected to “method.” In line 2, “a CD antigen” should be corrected to “a CD antigen.” In line 4, “DC40” is presumed to be a typographical error for “CD40,” and if so, should be corrected.
Regarding claim 87: there is an extra comma after “nucleic acid-binding domain” in line 7.
Appropriate corrections are required.
Claim Interpretation
The phrase “intravesicular polypeptide” is defined in the specification as “the polypeptide portion of the recombinant polypeptide that extends internally to the EV” (para 444).
Claim Rejections - 35 USC § 112(b)
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 1 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.
Claim 1 recites the limitation "said at least one target molecule" in line 4-5. There is insufficient antecedent basis for this limitation in the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4-5, 7, 13-14, 18, 23, 222, and 223 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Leonard (WO/2019/199941; cited in IDS filed 7/12/2022).
Leonard discloses a method of using the extracellular vesicles for delivering agents to target cells in vivo (para 3, 5, 81) (claim 1). The extracellular vesicles comprise an engineered targeting protein that targets the extracellular vesicles to a target cell, tissue, or pathway (para 6). The targeting protein is a fusion protein that includes an affinity agent (reads on targeting moiety), a transmembrane domain that orients the fusion protein in the membrane of the extracellular vesicles (reads on EV-anchoring polypeptide), and an engineered tag, such as an artificial epitope at its N- or C-terminus (reads on intravesicular polypeptide) (para 6, 31-33) (claims 1, 4). The extracellular vesicle is produced by transfecting a producer cell (para 57) (claim 1).
Leonard discloses that the EV-directed transmembrane polypeptide may be a transmembrane domain of VSVG (para 41) (claim 5). Leonard discloses that the extracellular vesicles may be a part of a pharmaceutical composition to be administered to a patient to treat a disease or disorder (para 58) (reads on mammalian cell of claim 7). Leonard discloses EVs that display anti-CD2 scFV (Abstract, para 15,19-20, 28, 137-142) (claims 13-14, 18). Leonard discloses that the fusion protein may comprise a structure as follows: Nter- signal peptide-scFV-transmembrane domain-Cter (para 13) (claim 23).
Leonard discloses that the extracellular vesicles comprise a cargo protein or RNA, which is separate from the recombinant polypeptide, wherein the cargo is an RNA that binds to an RNA-binding domain on the recombinant polypeptide (Figure 3; para 13, claim 18) (claim 222). Leonard discloses that the nucleic acid encoding the recombinant polypeptide may be present in expression vectors (para 82) (claim 223).
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.
Claim(s) 1 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Leonard (WO/2019/199941; cited in IDS filed 7/12/2022), in view of Zhang (US20200405640A1).
The teachings of Leonard are set forth above. Leonard anticipates claim 1.
Regarding claim 45: Leonard does note teach the method of claim 1, wherein said at least one targeting moiety comprises at least two targeting moieties, optionally wherein said at least two targeting moieties specifically bind to at least two different target molecules.
Zhang teaches extracellular vesicles that redirect immune effector cells towards cancer cells for killing (Abstract). Zhang teaches a polynucleotide encoding a fusion polypeptide comprising an immune effector cell binding domain or an antigen binding domain, a linker polypeptide, and an exosome addressing domain (para 16). Zhang teaches that the extracellular vesicles can comprise one or more antigen binding domains (reads on targeting moieties), which may be different from one another (para 159, 161, 207).
It would have been prima facie obvious for a person of ordinary skill before the effective filing date of the claimed invention to have modified the method of Leonard by using a polypeptide comprising at least two targeting moieties, as taught in Zhang. One of ordinary skill in the art would have been motivated to make this modification to obtain an engineered extracellular vesicle that can target two different target molecules, as taught in Zhang (para 161). One of ordinary skill in the art would have had a reasonable expectation of making this modification because Zhang teaches that an engineered extracellular vesicle can comprise one or more antigen binding domains.
Claim(s) 1, 87, and 91-93 are rejected under 35 U.S.C. 103 as being unpatentable over Leonard (WO/2019/199941; cited in IDS filed 7/12/2022), in view of Jang (US20210322327A1), as evidenced by Neumann (Acta Crystallographica Section D: Structural Biology, 2024, 80(5): 350-361).
The teachings of Leonard are set forth above. Leonard anticipates claim 1.
The phrase “intravesicular polypeptide” is defined in the specification as “the polypeptide portion of the recombinant polypeptide that extends internally to the EV” (para 444).
Leonard does not teach the method of claim 1, wherein said intravesicular polypeptide comprises an immunomodulatory molecule.
Jang teaches a method of producing extracellular vesicles comprising STING agonists (Abstract, para 411). Jang teaches that STING agonists can be encapsulated in EVs, such as exosomes, via any appropriate technique known in the art, including transfection and transduction (para 411). Jang teaches that the STING agonist may be a cyclic dinucleotide, including cyclic di-AMP (c-di-AMP) (para 303) (claim 92). Neumann shows that CdaA is a bacterial cyclase that synthesizes c-di-AMP (Abstract) (claim 93). Jang teaches that exosomes encapsulating or associated with a STING agonist can, upon administration to a subject in need, modulate the human immune system, and that such compositions can be used to treat a plurality of diseases or conditions wherein a modulation of the STING signaling pathway is of beneficial effect, including treatment of tumors or cancerous lesions in human subjects (para 4).
It would have been prima facie obvious for a person of ordinary skill before the effective filing date of the claimed invention to have modified the method of Leonard by incorporating CdaA, which is a bacterial dinucleotide cyclase which is a STING pathway activator, as taught by Jang. One of ordinary skill in the art would have been motivated to make this modification because Jang teaches that exosomes comprising a STING agonist can be used to treat diseases and conditions in vivo, including treatment of tumors in human subjects (para 4). One of ordinary skill in the art would have had a reasonable expectation of making this modification because Jang teaches that a STING pathway activator can be encapsulated in an exosome by transfection and transduction (para 411).
Claim(s) 1 and 223-224 are rejected under 35 U.S.C. 103 as being unpatentable over Leonard (WO/2019/199941; cited in IDS filed 7/12/2022), in view of Wang (US20210161817A1).
The teachings of Leonard are set forth above. Leonard anticipates claims 1 and 223.
Regarding claim 224: Leonard teaches that the vector comprising the nucleic acid encoding the recombinant vector may be a viral vector (para 84), but does not specify that it is an oncoviral vector. Leonard teaches that “suitable production cells” may be used as the producer cell (para 57), but does not specify that the producer cell is a tumor cell.
Wang teaches a method of using extracellular vesicle compositions for targeted delivery of a therapeutic agent to particular cells in a subject, including targeted delivery of drugs in the treatment of cancer (Abstract). Wang teaches that the exosome-producing cell may be a cancer cell (para 129). Wang teaches that the viral vector may be an adenovirus vector (reads on oncolytic virus vector) (para 122).
It would have been prima facie obvious for a person of ordinary skill before the effective filing date of the claimed invention to have modified the method of Leonard by using an adenoviral vector, as taught in Wang. One of ordinary skill in the art would have been motivated to make this modification because Wang teaches that if the exosome producing cell is a cancer cell, it is naturally loaded with tumor-cell associated antigens or antigenic fragments thereof (para 129). One of ordinary skill in the art would have had a reasonable expectation of making this modification because Wang teaches that a cancer cell can be used as a producer cell and that an adenovirus vector can be used as the viral vector in the EV delivery system taught therein.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632