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 in the reply filed on 10/10/2025 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)).
Accordingly, Claims 136, 137, 139, 140, 143, 144 and 146 are withdrawn from consideration for being directed to non-elected subject matter. Claims 77, 78, 84, 85, 87, 89, 90, 96, 99, 105, 106, 144 and 146 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/15/2024 and 10/10/2025 have been considered by the examiner.
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 105, 106 and 148 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.
Claim 105 is rejected because it depends on claim 76, a canceled base claim. MPEP 608.01 (n)(v) set forth that if the base claim has been canceled, a claim which is directly or indirectly dependent thereon should be rejected as incomplete. As such, claim 105 is rejected for being indefinite because the claim is not complete.
Claim 106 depends on claim 105, thus it is also incomplete.
Regarding claim 148, the claim depends on claim 136, which is a method, not a composition. The recitation of “the composition of claim 136” renders this claim indefinite because is unclear whether the claimed subject matter is a method as in claim 136 or a composition as recited in claim 148.
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.
(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) 77, 78, 84, 85, 89, 90, 96 and 147 is/are rejected under 35 U.S.C. 102(a1) as being anticipated by Kubuschok et al (IDS).
Claim 77 is drawn to a composition comprising nucleated cells that comprises an exogenously mutated Ras antigen or an exogenous nucleic acid encoding the mutated Ras antigen.
Kubuschok et al. teach spontaneous lymphoblastoid cell lines (SP-LCL) were established from pancreatic cancer patients and transfected with mutated Ras (page 817, 1st col., last paragraph), and long term culture of said cell lines were established (page 817, 2nd col., 1st paragraph, last line). Since SP-LCL cells are nucleated cells, said cells transfected with nucleic acid encoding mutated Ras, therefore, it anticipates the claimed invention of claim 77.
Regarding claim 78, since the specification does not define the term “perturbation,” electroporation of the SP-LCL cells with plasmid DNA encoding mutant Ras (page 817, 1st col., last paragraph), meets the limitation of “the nucleic acid encoding mutant Ras entered the nucleated cell through perturbation.”
Regarding claim 84, the wherein clause is not given weight because it is unclear what structural change the nucleated cells would have when they pass through multiple constrictions arranged in series and/or in parallel. The specification teaches the constriction of the cell is intended for a transient opening of the membrane pore so that mutant Ras may enter the cell (see page 71-72, bridging paragraph). As such, it is reasonable to interpreted that the pore of the nucleated cell would close following the introduction of mutated Ras. Therefore, the prior art disclosed cell still read on the claimed composition even though it may have passed through serial and/or parallel constriction.
Regarding claims 85 and 89, the SP-LCL cells taught by Kubuschok are immortalized B lymphocytes (page 816, 2nd col., 3rd paragraph), which meets the limitation of being immune cells and B cells.
Regarding claims 90 and 96, Kubuschok teaches Ki-Ras oncogene is selected as model tumor antigen because many human cancers harbor point mutations in the Ras gene at codon 12 (bridging paragraph of 1st and 2nd col., page 816). Kubuschok teaches plasmid carrying Ras mutation G12D and G12V are generated for transfection (page 817, 1st col., 3rd paragraph).
Regarding claim 147, the mutated Ras taught by Kubuschok is a tumor antigen (see title).
Claim(s) 77, 84, 85, 89 and 147 is/are rejected under 35 U.S.C. 102 (a1)(a2) as being anticipated by Nicolai (WO2013/149167).
Nicolai teaches a method of generating viral vector that comprising a polynucleotide encoding an exogenous antigen, a polynucleotide encoding a Sindibis E2 glycoprotein that preferentially binds dendritic cells expressing DC-SIGN, and a polynucleotide encoding a Vpx protein or a Vpr protein that retains SAMHD1-inhibiting activity (page 3, lines 1-5). Nicolai teaches the antigen may be a tumor antigen including mutated Ras (page 3, paragraph [0013], line 9). Nicolai teaches that viral vector may contact the target cells in vitro, wherein the target cells are typically populations of cells comprising dendritic cells from a subjects in whom it is desired to stimulate response from an antigen (paragraph [0175], lines 1-4). Nicolai teaches that target dendritic cells obtained from a patient and transduced with a recombinant virus containing a polynucleotide that encodes the desired antigen (paragraph [0186]). The teaching from Nicolai thus teaches at least a dendritic cell that comprises exogenous nucleic acid encoding mutated Ras, and anticipates claims 77, 85, 89 and 147.
Regarding claim 84, the wherein clause is not given weight because it is unclear what structural change the nucleated cells would have when they pass through multiple constrictions arranged in series and/or in parallel. The specification teaches the constriction of the cell is intended for a transient opening of the membrane pore so that mutant Ras may enter the cell (see page 71-72, bridging paragraph). As such, it is reasonable to interpreted that the pore of the nucleated cell would close following the introduction of mutated Ras. Therefore, the prior art disclosed cell still read on the claimed composition even though it may have passed through serial and/or parallel constriction.
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.
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) 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kubuschok, in view of Nicolai.
The teaching from Kubuschok has been discussed above. Kubuschok further teaches “in view of the potent stimulatory capacity of mutant Ras-LCLs, it is important to evaluate their role in comparison to consider the option to combine both APCs for immunization.” Kubuschok teaches that this is due to the observation that mutated Ras-LCLs alone are not able to prime naïve T lymphocytes against mutated Ras, only secondary response that is predominated by CD8+ T lymphocytes, whereas peptide pulsed dendritic cells can prime naïve T lymphocytes, indicating that a combination of tumor antigen presenting DCs and LCLs may be another possible vaccination strategy (page 826, 1st col., 2nd paragraph).
However, Kubuschok does not demonstrate a plurality of PBMC nucleated cells that comprise two or more of cell types including B cell and dendritic cells.
The teaching from Nicolai has been discussed above.
It would have been obvious to an ordinary skilled in the art to recognize that vaccine strategy including both LCLs and DCs expressing tumor antigen, mutated Ras may be more effective as immunotherapy for treating tumor with Ras mutation based on the teaching from Kubuschok as discussed in Kubuschok’s teaching. The ordinary skilled in the art reading Nicolai would know how to design vectors expressing tumor antigen to target specially to DC for efficient antigen presentation. The ordinary skilled in the art would have reasonable expectation of success for introducing mutated Ras into both DCs and B cells following combined teaching from Kubuschok and Nicolai. Therefore, the claimed invention of claim 87 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Allowable Subject Matter
Claim 99 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637