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, 14, 15, 21, 22, 24, 32, 34, 36, 45-47, 50 and 54-58.
Applicants' arguments, filed 02/06/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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, 46, and 56 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.
The claims fail to further limit the subject matter of the claim upon which it depends since these claims recite wherein the cargo comprises a therapeutic agent, which is broader in scope from the nucleic acid and polypeptide recited in claims 1 and 50.
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.
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.
Claims 1, 14, 15, 21, 22, 24, 32, 34, 36, 45-47, 50 and 54-58 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), as evidenced by Basler et al. (WO 2020/210003 A2, Oct. 15, 2020) (hereinafter Basler).
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,
The combined teachings of Mangeot, Selaru, Cheng, and Walfish do not disclose 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.
In regards to instant claims 45 and 55 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.
In regards to instant claims 1 and 50 reciting Henipavirus F and G proteins, as evidenced by Basler, Nipah virus F and G proteins are a species of henipavirus (equivalent abstract).
Response to Arguments
Applicant argues that the Office provides conclusory statements that it would be obvious for the skilled artisan to combine these references together.
The Examiner disagrees and does not find Applicant’s argument to be persuasive. The motivation statements provided in the rejection are: (1) 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; (2) 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; (3) 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; and (4) 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.
None of these motivation statements are conclusory since they are supported by the prior art. Also, Applicant has not explained how they are conclusory statements. As such, Applicant’s argument is unpersuasive.
Applicant argues that the Office provides no evidence that the Nipah virus F or G proteins of Cheng have any recognized suitability for use in fusosome compositions comprising a cargo, much less fusosome compositions having the specific features recited in the pending claims.
The Examiner does not find Applicant’s argument to be persuasive. Obviousness does not require absolute predictability. See MPEP 2143.02(II). Thus, it is not required for Cheng to specifically disclose that it is suitable for Mangeot’s fusosome composition comprising a cargo. As discussed in the rejection, 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. Applicant has not identified any features of Cheng that teaches away from this modification. As such, Applicant’s argument is unpersuasive.
Applicant argues that Cheng provides no express teaching that would lead the skilled artisan to choose the fusion proteins of Nipah virus for use in a fusosome over fusion proteins from any of the other viruses discussed therein.
The Examiner does not find Applicant’s argument to be persuasive. Selecting from a finite number of identified, predictable solutions is obvious according to MPEP 2143(I). Applicant has not shown wherein fusion proteins of Nipah virus is advantageous over fusion proteins from other viruses. Therefore, selecting fusion proteins of Nipah virus remains obvious. As such, Applicant’s argument is unpersuasive.
Applicant argues that Cheng provides no teaching that Nipah virus F and F proteins provide an advantage or expected beneficial result over the fusion proteins of Mangeot.
The Examiner does not find Applicant’s argument to be persuasive. Selection of a known material based on its suitability for its intended use supports a prima facie case of obviousness according to MPEP 2144.07. Thus, it would have been obvious to have used other fusion proteins besides the ones disclosed by Mangeot based on suitability. This is further supported by MPEP 2144.06 stating wherein it is obvious to substitute equivalents known for the same purpose. As such, Applicant’s argument is unpersuasive.
Applicant argues that impermissible hindsight reconstruction was used.
The Examiner does not find Applicant’s argument to be persuasive. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Applicant has not shown wherein Applicant’s disclosure was used. As such, Applicant’s argument is unpersuasive.
Conclusion
Claims 1, 14, 15, 21, 22, 24, 32, 34, 36, 45-47, 50 and 54-58 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TRACY LIU/Primary Examiner, Art Unit 1614