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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Nov. 10, 2025. Claims 1, 3-6, 8, 10, 14, 16. 18-21, 23, 25, 29, 31 and 33-37 are pending. Claims 3-4, 18-19, 31 and 33-37 are withdrawn. Claims 1, 5-6, 8, 10, 14, 16, 20-21, 23, 25 and 29 are currently examined.
Claim Objection
(Previous objection- withdrawn) Claim 10 is objected to because of the following informalities: The phrase “and further wherein the wherein the T cell receptor comprises CD3, CD4, or CD8;” contains a duplicate term “wherein the”.
This objection is withdrawn in view of the amendment filed on Nov. 10, 2025.
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.
(Previous rejection- withdrawn) Claims 1-2, 5-6, 8, 10, 14, 16-17, 20-21, 23, 25 and 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite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.
This rejection is withdrawn in view of the amendment filed on Nov. 10, 2025.
Claim Rejections - 35 USC § 112 (Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Previous rejection- withdrawn) Claims 1-2, 5-6, 8, 10, 14, 16-17, 20-21, 23, 25 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is withdrawn in view of the amendment filed on Nov. 10, 2025.
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.
(Previous rejection- maintained with edition) Claims 1, 5-6, 8, 10, 14, 16, 20-21, 23, 25 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Situ et al. ( Virology. 2018 Dec; 525:170-181).
The base claim 1 is directed to a gene delivery system comprising a lentiviral gene delivery vector particle comprising a polynucleotide encoding at least one gene-of-interest, wherein the lentiviral gene delivery vector comprises a modified Sindbis virus envelope protein comprising at least one mutation that renders the Sindbis virus envelope protein unable to bind a cell surface protein on a target cell; and at least one bispecific polypeptide comprising a first binding domain for the modified Sindbis virus envelope protein and a second binding domain for a target cell-specific receptor protein.
The base claim 16 is directed to a composition comprising a lentiviral gene delivery vector particle comprising a polynucleotide encoding at least one gene-of-interest, wherein the lentiviral gene delivery vector comprises a modified Sindbis virus envelope protein comprising at least one mutation that renders the Sindbis virus envelope protein unable to bind a cell surface protein on a target cell; and at least one bispecific polypeptide comprising a first binding domain for the Sindbis virus envelope protein and a second binding domain for a target cell-specific receptor protein.
Situ et al. discloses two lentiviral vectors system by pseudotyping the vectors with modified Sindbis virus envelope proteins, where the antibody such as anti-hTfR1 antibody can bind both lentiviral pseudoparticle and the target cell expressing the cell surface protein hTfR1 simultaneously. One of the systems Situ et al. taught is the 2.2 pseudotype that contains the ZZ peptide inserted into the E2 protein of the Sindbis virus. The ZZ peptide binds the Fc region of antibodies and the antibody can bind to a receptor such as hTfR1 of a target-cell. Another system Situ et al. taught is the E2 71 AV, STAV, eMA, and mSAH pseudotypes that are inserted with avidin streptavidin, monomeric rhizavidin, and the monomeric streptavidin/rhizavidin, respectively, in E2. These molecules are known to bind biotin. Therefore, the E2 71 AV, STAV, eMA, and mSAH pseudotypes are expected to be conjugated with biotinylated antibodies and the antibody such as anti-hTfR1 antibody to bind to the target-cell receptor (See page 4, paragraph 5; Fig. 1, page 20 and below). Situ et al. also teaches the “gene-of-interest” is a reporter gene of EGFP (See e.g. page 6, paragraph 2 and Fig. 3).
Furthermore, Situ et al. teaches that they have successfully used targeting lentiviral vector system with the ZZ domain for specific transduction of desired cell types in immunodeficient mice, demonstrating the proof of principle of the targeted lentiviral transduction. High stability of binding between E2 71 eMA and mSAH and biotinylated ligands will enable this targeting lentiviral transduction system to be applicable to immunocompetent animal experimental settings, facilitating application of targeted lentiviral transduction to broad fields of research (See page 11, paragraph 2). Here the animal transduction experiment indicates an administration of a composition of the pseudotyped lentiviral vector to the subject, which teaches claim 16 for “a composition comprising a viral gene delivery vector particle” as claimed.
Accordingly, Situ et al. anticipates the amended base claims 1 and 16 by teaching a gene delivery system/composition comprising a lentiviral gene delivery vector, a modified Sindbis virus envelope protein being unable to bind its original receptor-binding regions through E2 insertion, and a bispecific antibody that can bind the viral vector and a target cell-specific protein (See Fig. 1 below). Here the target-cell specific receptor protein is hTfR1, the viral gene delivery vector particle is a lentivirus and the bispecific polypeptide is an anti-hTfR1 antibody. Although Situ et al. does not explicitly adopt the term “bispecific polypeptide” as claimed, the teaching of the antibody in Situ is actually a “bispecific polypeptide” because the anti-hTfR1 antibody applied in the Situ’s study is used to bind both the target-cell receptor hTfR1 and the modified E2 of Sindbis virus, where the E2 is inserted with ZZ peptide or conjugated with a biotin-binding protein (See page 28).
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Regarding claims 5, 6, 8, 20-21 and 23, Situ et al. teaches that the bispecific polypeptide is an anti-hTfR1 antibody (See page 28 and below), which teaches claims 5 and 20. Here the hTfR1 antibody is an anti-human TfR1 antibody (claims 6 and 21). Because the E2 of Situ et al. is modified, the anti-hTfR1 antibody is considered to bind the Sindbis virus envelope protein in the E2 domain of the modified Sindbis virus envelope protein, which teaches claims 8 and 23.
Regarding claims 10 and 25, Situ et al. teaches that they used the ZZ peptide, IgG Fc-binding peptide derived from protein A, as an adaptor molecule fused with the mutated Sindbis virus envelope protein (2.2, Fig. 1A and B) to non-covalently conjugate targeting antibodies to lentiviral vectors. Lentiviral vectors pseudotyped with 2.2 can be easily conjugated with antibodies against various target molecules, including CD4, Transferrin receptor 1 (TfR1), PSCA, CD19, CD20, DC-SIGN, CD34, and P-glycoprotein, by simply mixing the vectors with antibodies (See page 3, paragraph 3, and Fig. 1 above).
Regarding claim 14 and 29, Situ et al. teaches the gene-of-interest is a marker gene, EGFP. For example, Situ et al. teaches that since the titers are exceptionally high, it is possible that the EGFP expression of the cells transduced by the E2 71 eMA and SAH pseudotypes is mediated by pseudo-transduction, which is the binding of the EGFP protein associated with the vectors (See e.g., page 8, paragraph 2).
Responses to Applicant’s Remarks
Applicant’s arguments filed on Nov. 10, 2025 has been received and fully considered.
Applicant’s amendment on claim objection is considered and the objection is withdrawn.
Applicant’s argument for rejections under 35 U.S.C. § 112 (a) and 112 (b) are considered and the rejections are withdrawn.
Applicant’s arguments for the rejection under 35 U.S.C. § 102 is not found persuasive for the following reasons:
1). Applicant argued that “Applicant’s invention is shown in "Sindbis virus Env" on the top left, whereas Situ is on the top right” based on Situ’s Fig. 1 (See Remarks, page 3). It is not clear what the exact direction the applicant referred to. Nevertheless, the “left” or “right” location is not required in the claims.
2). Applicant argued that “…at a minimum, Situ fails to teach or suggest the claim elements of a) a lentiviral gene delivery vector comprising a modified Sindbis virus envelope protein comprising at least one mutation that renders the Sindbis virus envelope protein unable to bind a cell surface protein on a target cell” (See Remarks, page 3).
This is not persuasive because Situ teaches that several receptor-binding regions of E2 to eliminate its original tropism through mutation /insertion (See pages 3, paragraph 1 and page 4, paragraph 3).
3). Applicant argued that “… the system described by Situ requires the addition of a binding domain (monomeric rhizavidin or streptavidin) against biotin on the Sindbis virus envelope protein (See Remarks, page 3).
This is not persuasive because the amended claims do not limit the binding position in the antibody as well as the claims use the term “comprise” in the claim, which cannot limit the binding format. Also, the antibody can bind ZZ peptide directly in a construct 2.2 (See Fig.1 above).
4). Applicant argued that “There is no teaching in Situ of a bi-specific polypeptide comprising a first binding domain that can directly bind Sindbis virus envelope protein without having first modified the Sindbis virus envelope protein also to contain monomeric rhizavidin or streptavidin”
This is not persuasive because the amended application claims “a first binding domain is the modified Sindbis virus envelope protein “without limiting what part of the modified protein. Situ modified the E2 protein by an insertion that is a modified Sindbis virus envelope protein as claimed.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672