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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/01/2023 was filed before the mailing date of the first non-final action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 16-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature judicial exception without significantly more.
Regarding claims 16-23, the claims are directed to a cell composition comprising immature blood cells expressing GPR56.
The claims are directed to a composition of matter, which is a statutory category of invention.
(Step 1: YES).
The claims are then analyzed to determine whether it is directed to any judicial exception. The claims are directed to a composition comprising immature blood cells expressing GPR56, wherein the said cells are human cells. Because there is no difference between the claimed and naturally occurring immature blood cells expressing GPR56, the claimed cells do not have markedly different characteristics, and thus are a “product of nature” exception. Thus, the claims recite at least one exception, which may be termed a product of nature. (Step 2A prong 1: YES).
The claims are then analyzed to determine if additional elements integrate the
judicial exception into a practical application. The claims recite no additional elements
and are limited to immature blood cells expressing GPR56 that are human in origin. (Step 2A prong 2: NO). Therefore, the claims are directed to a law of nature judicial exception and do not qualify as eligible subject matter.
The claims are patent ineligible.
Claim interpretation
Claim 1 is directed to a method of extracting GPR56 expressing cells from a cell aggregate containing immature blood cells. As per the specification, examples of the immature blood cell include hematopoietic stem cells (HSC), hematopoietic progenitor cells (HPC), a common lymphoid progenitor cell, a B cell-NK cell progenitor , a common myeloid progenitor cell, an erythroid progenitor cell, and a granulocyte-monocyte progenitor cell. HSC or HPC is preferred.
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.
(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 1, and 3-9 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tokoro et al (Experimental Hematology,2018).
Regarding claims 1,3, and 8-9, Tokoro et al developed a novel monoclonal antibody against mouse GPR56 (57R2A) to study the expression and distribution of GPR56 protein in hematopoietic stem cells (HSC). Tokoro et al also teach a method of isolating GPR56 expressing cells from bone marrow mononuclear cells (BMMNCs) using flow cytometry. It should be noted that BMMNCs read on cells containing immature blood cells as they contain HSCs. Tokoro et al demonstrate that HSCs, including the CD34+ cell population, contain GPR56 expressing cells. ( See abstract, and Fig.2C). Therefore, the cells of Tokoro extracted from the BMMNCs using anti-GPR56 will inherently contain a fraction of cells that express CD34 along with GPR56. Tokoro et al further demonstrate the ability of the isolated cells expressing GPR56 to repopulate bone marrow when transplanted intravenously into healthy irradiated mice, suggesting that GPR56 can be used to positively select for HSCs. (See Fig.3, and sections “ Flow cytometry analyses of GPR56 in mouse hematopoietic stem/progenitor cells”, and “LTR assay of GPR56-expressing BMMNCs” on page 53 ).
Regarding claim 4, Tokoro et al do not explicitly demonstrate that the isolated GPR56 cells also express CD45. However, Tokoro et al state that “ the expression of GPR56 mRNA in the define mouse hematopoietic stem/progenitor cell populations were confirmed by BloodSpot, a public database of gene expression in hematopoiesis. The levels of GPR56 mRNA were higher in HSCs than in progenitors (Supplemental Figure E1), suggesting that GPR56 mRNA is highly expressed in mouse HSCs”. It should be noted from supplementary Fig.E1 that cell populations termed long-term self-renewing HSCs (LT-HSC-CD150+) and short-term self-renewing HSCs (ST-HSC-CD150-) are characterized by the expression of CD43 along with GPR56. ( See Supplementary Fig.1 on page 59). Therefore, the cells of Tokoro extracted from the BMMNCs using anti-GPR56 will inherently contain a fraction of cells that express CD43 along with GPR56.
Regarding claims 5-7, the claims recite a product-by-process limitation. Product-by-
process limitations are considered only insofar as the method of production imparts distinct
structural or chemical characteristics or properties to the 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. In this case, prior art has demonstrated that it is possible to isolate GPR56 expressing cells from different sources, such as BMMNCs. Tokoro et al , for example, teach a method of isolating cell expressing GPR56 from bone marrow mononuclear cells, and demonstrate that hematopoietic stem cells, including the CD34+ cell population, express GPR56 . Therefore, even if the source of GPR56 expressing cells were obtained from BMMNCs rather than pluripotent stem cells and their derivatives, the end products are the same (i.e. HSCs-expressing GPR56). Hence, the scope of dependent claims 5-7 is the same as claim 1 and is considered unpatentable over the prior art, even though the prior art product is made by a different process. Absent evidence to the contrary and the claims are considered obvious. See MPEP 2113.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 10-15 are rejected under 35 U.S.C. 103 as being unpatentable over Tokoro et al (Experimental Hematology,2018), in view of Lowe et al (Methods in Molecular Biology,2016), and Gupta et al (Current Protocols in Immunology,2014).
The teachings of Tokoro et al are set forth above. Tokoro et al anticipate claims 1, and 3-9.
Regarding claim 2, the teachings of Tokoro et al are set forth above. Tokoro et al do not teach a method for isolating GPR56 expressing cells from human cell aggregate. However, Tokoro et al state that “ The data from BloodSpot further suggest that the mRNA of human GPR56 is also expressed in HSCs, which are defined as Lin- CD34+ CD38- CD90”. ( See 1st column-last paragraph-on page 58). Also, attached is a figure adopted from BloodSpot online available data that shows the presence of GPR56 expressing cells in human HSCs. ( See Fig. below). Therefore, it would have been prima facie obvious to one with ordinary skill in the art to adapt the method of Tokoro et al for isolating GPR56 expressing cells from human HSCs. Tokoro et al provide an evidence that human HSCs also express GPR56 and state that “ the conserved expression profiles of mouse and human GPR56 indicate that the molecule has a conserved function in HSCs”. ( See page 58-1st column- last paragraph ).Thus, providing a motivation for to a person of ordinary skill in the art to use the method of Tokoro et al to extract cells expressing GPR56 from human immature blood cells, because Tokoro et al demonstrated that these cells has a high potential to repopulate the bone marrow of a recipient mice. In other words, claim 2 is combining prior art elements according to known methods to yield predictable results, namely the predictable result being the isolation of GPR56 expressing cells from human
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immature blood cells.
Regarding claims 10-13, and 15, the teachings of Tokoro et al are set forth above. Tokoro et al do not teach a method for inducing the differentiation of GPR56 expressing cells into mature blood cells. As discussed above, the teachings of Tokoro et al clearly demonstrate that GPR56 can be used to selectively sort for HSCs, evident by the ability of GPR56 expressing cells to repopulate the bone morrow of a recipient mice. It is submitted that inducing the differentiation of hematopoietic stem cells into mature blood cells are so well-known in the art that a person of ordinary skill in the art could easily conceive applying the well-known techniques to differentiate GPR56 expressing cells into lymphoid blood cells expressing CAR.
For example, Lowe et al teach an in vitro method for producing NK cells (which is a lymphoid cells) expressing CAR from HSCs. The method of Lowe et al involves the following steps:
Extracting HSCs from umbilical blood cord
Genetically modifying HSCs to express CAR,
Differentiating the CAR-HSC into mature NK cells by placing the said cells in NK differentiation medium. The method of Lowe et al further includes the step of expanding the generated CAR-NK cells, this reads on claim 15. ( See section 2 “ Materials).
Therefore, it would have prima facie obvious to one with ordinary skill in the art at the time the invention was filed to combine the teachings of Tokoro et al and Lowe et al to produce GPR56- derived CAR-NK cells. An ordinary skill in the art who had viewed Tokoro et al could have come across Lowe et al and immediately noticed the strong possibility of modifying the method of Tokoro et al to further include the step of inducing the differentiation of the extracted GPR56 cells into mature CAR-NK cells, as taught by Lowe et al, would have the predictable results of generating engineered cells that can be used in cell-based therapy. In other words, claims 10-13, and 15 are combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Regarding claim 14, following the discussion above, Tokoro et al also do not teach a method for inducing the differentiation of GPR56 expressing cells into mature myeloid cells.
Gupta et al et al teach in vitro methods for producing mature myeloid cells from HSCs (typically isolated from bone marrow or peripheral blood). Gupta et al teach HSC can be induced to differentiate into myeloid cells by culturing them in a medium containing a selective set of cytokines and interleukins. For example, Gupta et al teach a method for inducing the differentiation of HSCs into neutrophil. The method involves the following steps:
Extracting HSCs from mice femurs and tibiae and magnetically separating them to exclude lineage-positive cells.
The resulting population enriched for hematopoietic stem cells is then expanded in medium supplemented with SCF and IL-3 to yield high numbers of early myeloid progenitors plus promyelocytes.
Then G-CSF is added to the mixture to increase the number of promyelocytes; followed by a final induction with only G-CSF. ( See basic protocol 2, section 22F.5.5).
Therefore, it would have prima facie obvious to one with ordinary skill in the art at the time the invention was filed to combine the teachings of Tokoro et al and Gupta et al to produce GPR56- derived myeloid cells. An ordinary skill in the art who had viewed Tokoro et al could have come across Gupta et al and immediately noticed the strong possibility of modifying the method of Tokoro et al to further include the step of inducing the differentiation of the extracted GPR56 cells into mature myeloid cells, as taught by Gupta et al, would have the predictable results of generating myeloid cells that can be used in cell-based therapy. In other words, claim 14 is combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638