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 included in the prosecution are claims 1, 21, 22, 24, 36, 45-47, 54 and 59-67.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/02/2026 has been entered.
Applicants' arguments, filed 06/02/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 36 and 46 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 36 fails to further limit the subject matter of the claim upon which it depends since claim 1 limits the cargo to only having a nucleic acid or polypeptide (i.e., wherein the cargo is a nucleic acid or polypeptide) and claim 36 broadens the scope by including an exogenous protein, an exogenous nucleic acid, a cytosolic protein, or a membrane protein in the cargo.
Claim 46 fails to further limit the subject matter of claim 1 since claim 46 recites wherein the cargo comprises a nucleic acid or polypeptide which is already recited in claim 1. Also, claim 1 recites wherein the cargo is a nucleic acid or polypeptide, which does not allow the cargo to comprise additional compounds.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Since Applicant has not corrected the 112 issue, the rejection is maintained.
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.
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, 21, 22, 24, 36, 45-47, 54 and 63-67 are rejected under 35, U.S.C. 103 as being unpatentable over Mangeot et al. (US 2012/0322147, Dec. 20, 2012) (hereinafter Mangeot) in view of Selaru (US 2018/0028687, Feb. 1, 2018) (hereinafter Selaru), Cheng et al. (US 2015/0133420, May 14, 2015) (hereinafter Cheng), and Walfish et al. (US 2016/0011197, Jan. 14, 2016) (hereinafter Walfish).
Mangeot discloses a microvesicle secreted by a eukaryotic cell, wherein the microvesicle comprises a viral membrane fusion protein and a protein of interest (i.e., cargo) (i.e. polypeptide) (i.e., therapeutic agent) (¶ [0012]). The viral membrane fusion protein is overexpressed (¶ [0011]). The protein of interest may be an exogenous protein (¶ [0166]). The microvesicle secreted by the eukaryotic cell does not comprise any viral structural protein (¶ [0016]). The term “viral structural protein” refers to viral proteins that contribute to the overall structure of a capsid protein (¶ [0017]). The microvesicle may not contain any nucleic acid encoding for the protein of interest (¶ [0019]). Typically, the eukaryotic cell is a mammalian cell. Examples of suitable mammalian cells include HEK-293 cells (¶ [0020]). The microvesicles are considered to be exosome-like and have a size between 40 and 150 nm (¶ [0063]). The viral membrane fusion protein enables the microvesicles to efficiently deliver the material contained in said microvesicles to a target cell (¶ [0068]). The microvesicles can be used for vaccination purposes (¶ [0106]).
Mangeot differ from the instant claims insofar as not disclosing wherein microvesicles have a lipid bilayer and a lumen comprising cytosol from the source cell.
However, Selaru discloses wherein exosomes refers to a small membrane extracellular vesicle of ~30-300 nm diameter that is secreted from producing cells into the extracellular environment. The surface of an exosome comprises a lipid bilayer from the membrane of the donor cell and the lumen of the exosome is topologically the same as the cytosol from the cell that produces the exosome. The exosome contains proteins (¶ [0042]).
Mangeot discloses wherein the microvesicles are exosome-like. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art that the microvesicles of Mangeot comprises a lipid bilayer and a lumen comprising cytosol since exosomes comprises these components as taught by Selaru.
The combined teachings of Mangeot and Selaru do not disclose wherein the viral membrane fusion protein is Nipah virus protein F or G.
However, Cheng discloses wherein expression of Nipah fusion (F) and attachment (G) proteins by themselves induces pH-independent cell membrane fusion and 25HC inhibits virus-cell membrane fusion (¶ [0114]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. The microvesicles of Mangeot comprises a viral membrane fusion protein. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated Nipah F or Nipah G into the microvesicles of Mangeot since they are known and effective viral membrane fusion proteins as taught by Cheng.
The combined teachings of Mangeot, Selaru, and Cheng do not disclose wherein the microvesicles do not comprise a nucleus.
However, Walfish discloses wherein removing nuclei removes bulk of cellular DNA (¶ [0115]).
Mangeot discloses wherein the microvesicles do not contain any nucleic acid. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have removed the nucleus since this is a known method for not having nucleic acids as taught by Walfish,
In regards to the functional limitations recited in instant claims 1 and 63-67, as noted in Example 135 of the instant specification, “often, entry of complex biological cargo into target cells is accomplished by endocytosis. Endocytosis requires the cargo to enter an endosome, which matures into an acidified lysosome. Disadvantageously, cargo that enters a cell through endocytosis may become trapped in an endosome or lysosome and be unable to reach the cytoplasm. The cargo may also be damaged by acidic conditions in the lysosome. Some viruses are capable of non-endocytic entry into target cells; however, this process is incompletely understood. This example demonstrates that a viral fusogen can be isolated from the rest of the virus and confer non-endocytic entry on a fusosome that lacks other viral proteins.” Example 135 further discloses that there was “a significant delivery of Cre cargo by NivG+F fusosomes even when recipient cells were co-treated with Baf to inhibit endocytosis-mediated uptake.” Thus, since it appears that the claimed property is through a fusosome comprising a viral fusogen and Mangeot discloses microvesicles comprising a viral membrane fusion protein, the microvesicles of Mangeot would necessarily have the claimed properties when contacted with a target cell population.
In regards to instant claim 45 reciting a pharmaceutical composition, Mangeot discloses wherein the microvesicles can be used for vaccination purposes. Therefore, a pharmaceutical composition comprising the microvesicles with a pharmaceutically acceptable carrier would have been obvious.
2. Claims 59-62 are rejected under 35, U.S.C. 103 as being unpatentable over Mangeot et al. (US 2012/0322147, Dec. 20, 2012) (hereinafter Mangeot) in view of Selaru (US 2018/0028687, Feb. 1, 2018) (hereinafter Selaru), Cheng et al. (US 2015/0133420, May 14, 2015) (hereinafter Cheng), Walfish et al. (US 2016/0011197, Jan. 14, 2016) (hereinafter Walfish), and Khvorova et al. (US 2017/0183686, Jun. 29, 2017) (hereinafter Khvorova).
The teachings of Mangeot, Selaru, Cheng, and Walfish are discussed above. Mangeot, Selaru, Cheng, and Walfish do not teach wherein the microvesicles comprise a targeting moiety.
However, Khvorova discloses wherein exosomes can be specifically targeted to a desired cell type or tissue type by expression of a targeting peptide on the exosome surface. The targeting peptide can bind to a moiety present on the surface of the desired target cells (¶ [0138]). Targeting peptides can be selected to target particular tissue types such as brain. This can be achieved by using a targeting peptide that interacts with a neuronal cell surface marker (¶ [0140]). The targeting peptide can be localized to the surface of the exosome by expressing it as a fusion protein with an exosomal transmembrane protein (¶ [0141]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated a targeting peptide to the microvesicle of Mangeot motivated by the desire to have the microvesicle target a desired cell type such as brain cells as taught by Khvorova.
Response to Arguments
Applicant argues that none of Mangeot, Selaru, Cheng, Walfish, or Khvorova, alone or in combination, teach or suggest a delivery agent for delivery of cargo to a target call by a non-endocytic pathway, such as to a other than an endosome or a lysosome.
The Examiner does not find Applicant’s argument to be persuasive. As noted in Example 135 of the instant specification, “often, entry of complex biological cargo into target cells is accomplished by endocytosis. Endocytosis requires the cargo to enter an endosome, which matures into an acidified lysosome. Disadvantageously, cargo that enters a cell through endocytosis may become trapped in an endosome or lysosome and be unable to reach the cytoplasm. The cargo may also be damaged by acidic conditions in the lysosome. Some viruses are capable of non-endocytic entry into target cells; however, this process is incompletely understood. This example demonstrates that a viral fusogen can be isolated from the rest of the virus and confer non-endocytic entry on a fusosome that lacks other viral proteins.” Example 135 further discloses that there was “a significant delivery of Cre cargo by NivG+F fusosomes even when recipient cells were co-treated with Baf to inhibit endocytosis-mediated uptake.” Thus, since it appears that the claimed property is through a fusosome comprising a viral fusogen and Mangeot discloses microvesicles comprising a viral membrane fusion protein, the microvesicles of Mangeot would necessarily have the claimed properties when contacted with a target cell population. Thus, Applicant’s argument is unpersuasive.
Conclusion
Claims 1, 21, 22, 24, 36, 45-47, 54 and 59-67 are rejected.
No claims are allowed.
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/TRACY LIU/Primary Examiner, Art Unit 1614
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