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 .
Priority
Acknowledgement is made that the instant application is a divisional of US application number 16/622,237 (now US patent 11851677) which is a National Stage of International application No. PCT/US2018/037286 (filed 06/13/2018), which claims the benefits of US Provisional Application No. 62/519,123 (filed 06/13/2017).
Claim Objections
Claims 22, 23, 26, 28, 29, 31, 38, and 40 objected to because of the following informalities:
Claim 22 recites the abbreviation MCSF without defining the full term.
Claims 23 and 28 recite the abbreviation GvHD without defining the full term.
Claims 26, 29, 31, 38, and 40 recite the abbreviation GMCSF without defining the full term.
The full term should precede the first use of an abbreviation. Appropriate correction is required.
Claim Interpretation
Claims 22, 26, 28, 29, 33-35, and 38 use product-by-process language. Product-by-process claims are considered only in so far as the process of production affects the final product. Therefore, if the product as claimed is the same or obvious over a product of the prior art (i.e., is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113.
Regarding claim 22: Claim 22 is drawn to a method of treating a subject in need of cell therapy comprising administering a therapeutically sufficient number … of induced myeloid suppressive cells. The induced myeloid suppressive cells are obtained by directing differentiation of induced definitive hemogenic endothelium cells (iHE) with a medium composition comprising a ROCK inhibitor and MCSF. The specification of the instant application teaches differentiation of hiPSCs to CD34+ hemogenic endothelium (See ¶000160-000161). The induced CD34+ hemogenic cells are further differentiated in myeloid differentiation media comprising VEGF, bFGF, SCF, IL3, FLT3L, MCSF, GMCSF, StemRegenin 1, and ROCK inhibitor (See ¶000162 and Table 5). The resulting cells were CD45+ and predominately expressed myeloid marker CD33 (See ¶000163). Therefore, the myeloid suppressive cells of claim 22 are understood to require CD45+ cells.
Regarding claims 26, 29: Claim 26(a) and (b) and Claim 29(a) further define the medium composition used to differentiate iHEs to MDSCs. The specification teaches induced CD34+ hemogenic cells are further differentiated in myeloid differentiation media comprising VEGF, bFGF, SCF, IL3, FLT3L, MCSF, GMCSF, StemRegenin 1, and ROCK inhibitor (See ¶000162 and Table 5). The resulting cells were CD45+ and predominately expressed myeloid marker CD33 (See ¶000163). Therefore, the myeloid suppressive cells derived in a medium comprising the limitations of 26(a) and (b) are understood to require CD45+ cells.
Regarding claim 28: claim 28(d) required the limitation of deriving iHE cells from iPSCs. The specification of the instant application teaches using iPSC derived iHEs to produce CD45+ MDSCs. Therefore 28(d) requires CD45+ MDSCs. Claim 28(e) require using thiazovivin or Y27632 as the ROCK inhibitor in the myeloid differentiation media. There is no evidence that the identity of the ROCK inhibitor would result in MDSCs which are different from CD45+ MDSCs. Therefore 28(e) requires CD45+ MDSCs.
myeloid marker CD33 (See ¶000163). Therefore, the myeloid suppressive cells derived in a medium comprising the limitations of 29(a) are understood to require CD45+ cells.
Regarding claims 33-35: Claim 33 further defines the method of deriving iHE cells from iPSCs. The specification of the instant application teaches using iPSC derived iHEs to produce CD45+ MDSCs. In the absence of evidence to the contrary, the method by which the iHEs are derived from iPSCs does not lead to MDSCs which are different from CD45+ MDSCs. Furthermore, while claims 33-35 depend from claim 28, limitations (a)-(f) of claim 28 are presented as alternatives and therefore the broadest reasonable interpretation of the MDSC of claim 28 is a CD45+ MDSC.
Regarding claims 38-40: Claims 38-40 further defines the medium composition used to differentiate iHEs to MDSCs. The specification teaches induced CD34+ hemogenic cells are further differentiated in myeloid differentiation media comprising VEGF, bFGF, SCF, IL3, FLT3L, MCSF, GMCSF, StemRegenin 1 (reads on AhR antagonist), and ROCK inhibitor (See ¶000162 and Table 5). The resulting cells were CD45+ and predominately expressed myeloid marker CD33 (See ¶000163). Claim 38 depends from claim 37 and thus is understood to require MDSCs that are CD45+ and CD33+
Claim Rejections - 35 USC § 112(b)
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.
Claims 26-28 and 31 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 26-28 recites the limitation "the population of induced myeloid suppressive cells". There is insufficient antecedent basis for this limitation in the claim.
Claim 31 recites the limitation "the " in line 12. There is insufficient antecedent basis for the adhesion molecule in the claim.
Appropriate correction is required.
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.
Claims 22, 23, 26-29, 33-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Messmann et al (Blood, 2015).
Messmann et al teach a method for treating graft-versus-host disease (GVHD) in a murine allogeneic bone marrow transplantation model (See abstract). GVHD targets organs such as lung and liver (See MDSC treatment induces the induction of type 2 T cells). The method comprises transplantation of CD45.1+ Myeloid-derived suppressor cells (MDSCs) generated from bone marrow, in vitro (See abstract and Fig. 3). After 4 days of culture, Messman et al detected 92% of the cells differentiated into MDSCs and 66% of MDSCs were monocytic (See Fig. 1). After MDSC transplantation, monocytic MDSCs were found to be the major population in the liver (See MDSC proliferate in vivo, reduce alloantigen-specific T-cell proliferation only insubstantially, and o not influence alloantigen-specific T-cell homing). Messmann teaches MDSCs inhibit T-cell expansion and functions (See abstract). Specifically, the in vitro generated MDSCs reduce alloantigen-specific T-cell proliferation early after transplantation (See Fig. 3)
Regarding claims 22, 26, 28, 29, 33-35: Messmann et al teach a method for treating GVHD in mice which reads on a method of treating a subject in need of cell therapy. The method comprises transplanting in vitro derived CD45.1+ MDSCs which reads on administering a therapeutically sufficient number of cells wherein the cells comprise induced myeloid suppressive cells that are CD45+.
Regarding claim 23: Following the discussion of claim 22 above, Messmann et al teach a method for treating GVHD in mice which reads on a subject that has GVHD. Furthermore, Messmann teaches the in vitro generated MDSCs reduce alloantigen-specific T-cell proliferation after transplantation which reads on the administered cell comprising myeloid suppressive cell suppress T cell proliferation in vivo.
Regarding claim 27: Following the discussion of claim 22 above, Messman discloses differentiating bone marrow cells to MDSCs and obtaining a population that is 92% MDSC by day 4 of culturing. Messman further discloses the MDSCs comprise 66% monocytic MDSCs which reads on the population of induced immune regulatory cells comprises more than 90% iMDSCs wherein the iMDSCs comprise monocytic MDSCs.
Claims 22, 23, 26, 28, 29, 33-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (WO2012054747A2).
Chen discloses a composition and methods for treating tumors using isolated MDSCs in combination with oncolytic viruses, nanoparticles, or other anti-tumor agents (See abstract). The composition can be used to treat solid tumors (See ¶00107). The MDSCs of Chen can be derived in vitro from ES cells, HSCs or iPS cells using cytokines including GM -CSF,M-CSF, and/or G-CSF(See ¶0082-0083). The method of treating a tumor comprises administering to a patient in need of treatment a therapeutically effective amount of a pharmaceutical formulation comprising a MDSC, an anti-tumor agent, and a pharmaceutical carrier (See ¶0012). The anti-tumor agent can be The MDSCs further express CD33 (See claim 28). In Example 6, Chen discloses a series of experiments in which CD45.1+ MDSCs are used for adoptive transfer to mice carrying hepatic tumors (See¶00170). Additionally, in example 11, Chen discloses treatment with the NP-OVA-PGN-loaded MDSC decreased Treg activation in metastatic organs and spleen (See ¶00187).
Regarding claims 22, 26, 28, 29, and 33-35: Chen discloses a methods for treating tumors comprising administering a composition comprising MDSCs and an oncolytic virus, nanoparticle, or other anti-tumor agent which reads on a method of treating a subject in need of cell therapy comprising administering a therapeutically sufficient number of cell to the subject in need wherein the cells comprising myeloid suppressive cells. Chen further discloses the cells can be derived in vitro from HSCs or iPSCs. Additionally, Chen teaches examples using CD45.1+ MDSCs which reads on CD45+ MDSCs.
Regarding claims 23 and 25: Following the discussion of claim 22 above, Chen discloses the tumor can be a solid tumor. Additionally, Chen discloses an example in which treatment with the MDSC composition resulted in decreased Treg activation in metastatic organs and spleen which reads on suppressing T cell effector function in vivo.
Regarding claim 36: Following the discussion of claim 22 above, Chen discloses using isolated MDSCs which reads on obtaining the population of induced immune regulatory cells comprises isolating the induced myeloid suppressive cells.
Regarding claims 37-40: Following the discussion of claim 22 above, Chen discloses the MDSCs are CD45.1+ and CD33+ which reads on CD45+ and CD33+ MDSCs.
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.
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 22, 23, 26, and 28-35 are rejected under 35 U.S.C. 103 as being Chen (WO2012054747A2) in view of Torikai et al (Blood, 2013).
The teachings of Chen are set forth above.
Chen anticipates claims 22, 23, 26, 28, 29, and 33-35
Regarding claims 30-32: Chen discloses a method of treating a subject with a tumor comprising transplanting CD45+ MDSCs. Chen further discloses the cells can be derived from ESCs or iPSCs.
Chen does not disclose deriving MDSCs from iPSCs comprising genetically modified modalities contributing therapeutic attributes to the MDSCs.
Torikai et al discloses a method of eliminating HLA-A expression from embryonic stem cells (ESCs) using zinc finger nucleases (ZFN) targeting the HLA-A gene on 6p21 (reads on 31 a) the genetically modified modalities comprise deletion of any of the HLA genes in the chromosome 6p21 region) (See abstract and Fig. 1). Torikai et al further discloses deletion of HLA-A results in cells that can evade T-cell recognition and can therefore able to overcome rejection by a recipient without the need to suppress host immunity. The ability to overcome host immunity makes these cells useful for allografts (See Sec. Discussion). The ESCs of Torikai have therefore been genetically modified to modulate immune response (reads on claim 30)
Given that Chen discloses a method of treating a tumor comprising transplanting cells and Torikai et al discloses a method of deleting HLA-A in stem cells which allows the cells to overcome host immune responses, it would have been prima facie obvious to a person of ordinary skill in the art to use the HLA-A deleted ESCs of Torikai et al to produce MDSCs for use in the treatment method of Chen. One would have been motivated to differentiate MDSCs from the HLA-A deleted ESCs of Torikai et al for use in the treatment method of Chen because Chen is transplanting cells and Torikai et al discloses the HLA-A deleted cells are able to overcome host immunity and are therefore useful for allografts (reads on 32(ii)a therapeutic attribute of the source specific immune cells comprising HLA presentation or lack thereof). There is a reasonable expectation of success because Torikai et al disclose ESCs and Chen teaches the MDSCs can be derived from ESCs.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/ Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633