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 .
Claim Status
Claims 1-2, 4-5, and 51-53 are currently pending in this application.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-5, 7-9, 25, 29, 32, 35, 39, and 44, in the reply filed on July 9, 2024 is acknowledged. Claims 1-2, 4-5, and 51-53 have been considered on the merits.
Previous Rejections
Status of the rejections: previous rejections pursuant to 112(a) are moot in view of the claim amendments. The previous rejections pursuant to sections 102(a) and 103 are withdrawn in view of the claim amendments.
Claim Interpretation
Claim 1 recites the term “HSPCs,” which is interpreted to encompass any population of cells wherein the cells are hematopoietic stem cells, hematopoietic progenitor cells, or a combination of the aforementioned cell types. And thus, it follows that claim 2 is interpreted to require those hematopoietic stem cells, hematopoietic progenitor cells, or the combination thereof be CD34+. In claim 51, the term “GEMys” is interpreted as typically used in the art to mean genetically engineered myeloid cells, but in view of claim 1, restricted to only those myeloid cells that are also some type of myeloid progenitor cell (i.e., a subtype of hematopoietic progenitor cell) and which comprise the recited vector, i.e., the genetic engineering. See instant [0028], [0075]-[0077]). Similarly, claim 52 limits the HSPCs to consisting essentially of myeloid hematopoietic progenitor cells (“GEMys”) that have been genetically engineered to comprise the vector comprising the transgene (e.g., hematopoietic stem cell-derived, myeloid progenitor cells comprising the transgene as the genetic engineering).
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.
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.
Claims 1-2, 4-5, and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over Reid (Reid et al., Stem Cell Reports 10: 1625-41 (2018)) in view of Gautam (Gautam et al., Cancer Gene Ther 7: 1060-8 (2000)).
The claims are interpreted as provided in a previous section.
Reid teaches transplanting a hematopoietic cell population (HSC) to engraft donor hematopoietic stem cells into a subject after irradiation to suppress endogenous HSC and that HSC expressing CXCR4 exhibit improved in vivo survival and HSC function (Abstract). Further, Reid teaches primary hematopoietic cell populations (adult/somatic HPCs) express CXCR4, particularly from human cord blood (CB) (Fig. 3C, 3F-J; pg. 1628, right col., last para.; Fig. S2A, S2D; Fig. 4; Table S2), and that CXCR4 is a receptor critical for hematopoietic stem cell (HSC) function, such as regulating their proliferation and acting as the sole chemokine receptor for migration/chemotaxis (pg. 1638, left col.; pg. 1625, right col., 1st para.).
Reid does not teach wherein the primary somatic HSC are genetically modified to contain a vector comprising a transgene encoding IL-12.
However Gautam teaches transplanting an HSPC population (32DIL-12) into a subject wherein the cells are first transduced to comprise a vector expressing a transgene encoding an IL-12, such as for stably expressing IL-12 in the recipient to induce IFN- and NK cell activation as a therapeutic (Abstract; Fig. 1; Table 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to obtain a CXCR4+ primary HSPC population for use in HSC transplantation as taught by Reid wherein the cells are engineered for IL-12 expression from a vector with an IL-12 transgene as taught by Gautam, such as wherein the source is human cord blood. One of ordinary skill in the art preparing a hematopoietic stem and progenitor cell population with the goal of treating leukemia in a subject with a gene therapy approach by delivering IL-12 via transplanted hematopoietic progenitor cells would be motivated by Gautam teaching the IL-12 transgene protected subjects from leukemia and improved survival (e.g., > 60 days post-transplantation) (pg. 1063, right col., to pg. 1064; Table 3, Fig. 5) and by Reid teaching general preparations of hematopoietic stem cells for transplantation benefit from CXCR4 expression, as occurs in natural somatic HSC in vivo (pg. 1634, left col., to pg. 1636; Fig. 6-7; Table S3).
Regarding claim 2, Reid teaches wherein the primary somatic HSC are enriched for CD34+ (pg. 1628, right col., last para.; Fig. 3G-H).
Regarding claims 4-5, Reid teaches genetically engineering HSC using a lentivirus viral vector to stably express a transgene before transplantation (pg. 10 at Lentivirus transgene expression), which is at least equivalent to the retroviral vector for transgene expression in HSPC as taught by Gautam.
Regarding claim 51, Reid teaches CXCR4+ primary HSPC populations comprises GEMys, including ones capable of forming granulocytes (G), erythrocytes (E), and monocytes (M) (i.e., GEM or GM) (Fig. 1-2, S1).
Regarding claim 52, Reid teaches wherein that the HSPC population consists essentially of GEMys (e.g., CB-derived CD34+CD45+ HPCs preferentially committed to myeloid lineages) (Fig. 2E, S1A).
Regarding claim 53, Reid teaches using a transgene expression vector comprising an EF-1α or a CMV promoter for driving expression (pHIV(IRES)EGFP (Addgene #21373)) (pg. 1061, right col.). Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing wherein the cells are engineered for IL-12 expression using a pHIV(IRES)EGFP lentiviral vector as taught by Reid by operably linking the IL-12 transgene to the EF-1α promoter as a known element of the prior art for providing a routine use from the prior art.
Thus, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 6/8/26 regarding the previous art rejections (pg. 6-9) have been fully considered and found persuasive; however applicant’s claim amendments resulted in the new grounds of rejection laid out above.
Applicant’s response argues regarding novelty (pg. 5) that the intended use of the claimed composition renders it incompatible with the teachings of Gautam; however, the claims are directed to a product and not any process of using it, and thus this argument is unpersuasive. Further, a new ground of obviousness rejection is set forth herein wherein the composition may have completely different intended uses unrelated to injecting the cells into a human patient.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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