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
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 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.
Response to Amendments
Applicant’s amendments, IDS filed on Aug. 17, 2026, and response filed Aug. 6, 2026 have been received and entered into the case.
Status of the Claims
Claims 1, 4, 7-9, 11-12, 14, 16-18, 21, 25-27 and 30 are currently pending.
Claims 1, 4, 14, 16, 21, and 25 are amended.
Claims 7-9 and 11-12 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 2-3, 5-6, 10, 13, 15, 19-20, 22-24 and 28-29 are cancelled.
Claims 1, 4, 14, 16-18, 21, 25-27 and 30 have been considered on the merits.
Claim Objections
Specification objections are withdrawn due to amendment.
Claim Rejections - 35 USC § 112(a)
The claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ), are revised due to amendment.
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.
Claims 1, 4, 14, 16-18, 21, 25-27 and 30 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 enablement requirement. The claims contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification, describes generating cells overexpressing BCL11B, does not reasonably provide enablement for a method of treating a hematopoietic stem cell transplant (HSCT) patient with a T cell therapy comprising thymic T cell reconstruction in the patient following the HSCT, by administering the modified cells.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, the enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of a treating a HSCT patient with a T cell therapy by administering an amount effective to promote T cell reconstitution in the patient of either hematopoietic stem and progenitor cells (HSPCs) or pluripotent stem cells modified to have increased BCL11B expression to result in thymic T cell reconstruction in the patient following HSCT. Thus, the claims taken together with the specification imply that a HSCT patient can be administered an amount effective to promote T cell reconstitution in the patient of HSPCs or pluripotent stem cells which have been modified to have increased BCL11B expression and as a result the patient will have thymic T cell reconstruction.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The prior art in general teaches safety concerns for T cell therapy and off target toxicity. For instance, D’Ippolito et al. (Cancer Immunology, Immunotherapy, 2019) reports that engineered T cells has the risk of severe off target toxicities and that different safety strategies are needed for engineered T cells to remove the cells in case of adverse events, control the T cell activity and to improve target selectivity (abstract and pg. 1703 Col. 2 para. 3 to pg. 1706 Col. 1 para. 2). Zhang et al. (Journal of Hematology & Oncology, 2023) reports that TIL (tumor-infiltrating lymphocyte) therapy has not been approved by US Food and Drug administration, has the challenges of that not all tumor tissues are suitable for such treatment, the time it takes to produce enough lymphocytes for treatment is long, the TILs become exhausted and TIL therapy has to be customized (pg. 3 Col. 2). Zhang teaches that there are a number of TCR (T cell receptor)-T cell therapy challenges including on-target off-tumor toxicity, poor persistence of the cells, expression and correct pairing of engineered TCR cells, and handling the constraints of the TME (tumor microenvironment) (pg. 4 Col. 1 para. 2 to pg. 5 para. 2). Zhang teaches that current CAR-T therapy has many challenges to overcome with the treatment of solid tumors (pg. 15 Col. 2 para. 3). Thus, as the state of the art stands, the method would be unpredictable depending on the specific engineered T cell, the source of the T cell, the subject and the disease being treated.
(5) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The instant specification provides no working examples and guidance for a method of a treating a HSCT patient with a T cell therapy by administering a therapeutically effective amount of either HSPCs or pluripotent stem cells modified to have increased BCL11B expression. The applicants have provided no data demonstrating the claimed method with an animal model. Therefore, there is no conclusive evidence in the instant disclosure to indicate that the instantly claimed method can be used to treat a HSCT patient with a T cell therapy by administering a therapeutically effective amount of either HSPCs or pluripotent stem cells modified to have increased BCL11B expression.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the claimed invention as instantly claimed. Therefore, the claims are rejected under 35 U.S.C. 112, first paragraph, for a lack of enablement.
Claim Rejections - 35 USC § 112(b)
The claim rejections under 35 USC § 112, (b) or second paragraph (pre-AIA ), are withdrawn due to amendment and part of the claim rejections are maintained.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
The claim rejections under 35 USC § 103 are revised due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
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, 4, 14, 16-18, 21, 25-27 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Themeli et al. (US 2016/0009813 A1) (ref. of record) in view of Chen et al. (Human Immunology, 2012) (ref. of record), Valamehr et al. (US 2020/0069734 A1, priority to Dec. 22, 2017) (ref. of record) and Ha et al. (Leukemia, 2017) (ref. of record).
With respect to the first recited step of claim 1, Themeli teaches providing hematopoietic stem cells and pluripotent stem cells (0007, 0013 and 0156). With respect to the second recited step of claim 1, Themeli teaches modifying the cells so that the cells have increased proliferation, survival and function (0008 and 0123). With respect to the third recited step of claim 1, Themeli teaches incubating the modified cells in vitro under conditions sufficient for differentiation of T cells from the HSPCs and/or pluripotent stem cells and proliferation of T cells from the HSPCs and/or pluripotent stem cells to produce the engineered T cells (0008-0009, 0015, and 0105). With respect to the fourth recited step of claim 1, Themeli teaches administering the modified cells to a subject for T cell therapy (0011-0012).
With respect to claim 1 and the fourth recited step of claim 1, Themeli teaches the method where the subject has previously had allogeneic hematopoietic cell transplantation (the subject is a hematopoietic stem cell transplant (HSCT) patient and the T cell therapy comprises thymic T cell reconstitution in the subject following the HSCT and the modified cells are administered to the subject with HSCT, therefore the cells would be in an amount effective to promote T cell reconstitution (0020 and 0256). With respect to claim 4, Themeli teaches the T cell therapy is a chimeric antigen receptor (CAR) T cell therapy and the method further comprises transducing the pluripotent stem cells and hematopoietic stem cells, or the modified cells with a heterologous nucleic acid molecule encoding the CAR before administering the cells to the subject (0008-0009). With respect to claim 14, Themeli teaches obtaining the cells from the subject (0145).
With respect to second recited step of claim 1 and claim 17, Themeli teaches increasing expression of a protein of interest by transducing the HSPCs, pluripotent stem cells, or mature T cells with a heterologous nucleic acid encoding the gene of interest or by inserting the gene using gene editing technology (0014-0016, 0068, 0105 and 0231). With respect to claim 18, Themeli teaches increasing expression of a protein of interest by transducing the cells with a viral vector containing the nucleic acid encoding for the protein of interest operably linked to a promoter (0231). Themeli is silent with respect to the multiplicity of infection that the cells are transduced at and does not teach that it is between 1 and 10 as recited in claim 21. Although Themeli is silent with respect to the multiplicity of infection, one of ordinary skill in the art would recognize that the multiplicity of infection is a result effective variable and that the multiplicity of infection would be matter of routine optimization depending on the cells being transduced and the desired expression levels.
With respect to claim 25, Themeli teaches that the cells and subject are human (0078 and 0143-0144). With respect to claim 30, Themeli teaches that the cells are autologous or non-autologous (01280240).
Themeli does not teach the method where the BCL11B expression is increased in the HSPCs and pluripotent stem cells to form modified cells with increased BCL11B expression compared to corresponding control cells by introducing into the cells a heterologous nucleic acid encoding BCL11B, wherein the increased BCL11B expression enhances the function and/or persistence of engineered T cells from the HSPCs or pluripotent stem cells, or increases proliferation of the mature T cells compared to the corresponding control cells as recited in second recited step of claim 1. Likewise, Themeli does not teach the method where the BCL11B expression level in the modified cells is at least that of a control CD34+ or CD34-CD4+CD8+ human thymic T-cell precursor as recited in claim 15. Similarly, Themeli does not teach the method where the BCL11B expression level in the modified cells is increased 2 to 10-fold in the mature T cells compared to the BCL11B expression in corresponding control cells as recited in claim 16.
However, Chen teaches a method of providing T cells and modifying the T cells so that the T cells have increased BCL11B expression (abstract). Chen further teaches the overexpression of BCL11B in the cells resulted in increased proliferation ability of the T cells (abstract). With respect to claim 16, Chen teaches the method where the BCL11B expression level in the modified cells is increased 30-fold in the mature T cells compared to the BCL11B expression in corresponding control cells (pg. 458-459 bridging para.). In further support, Valamehr teaches a method of cell therapy including T cells where the subject is administered modified cells where iPSCs cells have been modified by introducing genes expression proteins that improve differentiation potential, antigen targeting, antigen presentation, antibody recognition, persistence, immune evasion, resistance to suppression, proliferation, co-stimulation, cytokine stimulation, cytokine production, chemotaxis and cellular cytotoxicity such as HLA class I proteins including BCL11B (0004, 0052, 0117 and 0180). In additional support, Ha teaches that BCL11B regulates the initial stages of human T-cell differentiation and is essential for T-lineage commitment (abstract, Fig. 1 and pg. 2512 Col. 1 para. 3). Ha further teaches transducing CD34+ CB (cord blood) progenitors (HSPCs) with BCL11B KD and culturing to induce T-lineage differentiation (Fig. 2 and pg. 2504 Col. 1 para. 3).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of Themeli to increase the expression of BCL11B in the hematopoietic stem cells and pluripotent stem cells for the benefit of increasing the proliferation ability and differentiation potential of the cells and to induce T-lineage differentiation as taught by Chen, Valamehr and Ha. It would have been obvious to one of ordinary skill in the art to modify Themeli to include other known modifications to the hematopoietic stem cells and pluripotent stem cells which improve proliferation of the cells and promote the differentiation of the cells into the T cell lineage such as increasing BCL11B expression, since the ability to improve the ex vivo expansion of cells of hematopoietic stem cells and pluripotent stem cells and the differentiation into T cells was known in the art and increased BCL11B expression was known to improve proliferation and differentiation of the cells as taught by Chen, Valamehr and Ha. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification in the method of Themeli, since Themeli teaches the method where a protein expression is increased so that the cells have increased proliferation, survival and function, Chen and Valamehr teaches that the overexpression of BCL11B in the hematopoietic stem cells, pluripotent stem cells and mature T cells results in increased proliferation ability and differentiation potential and Ha teaches BCL11B expression promotes the differentiation of progenitor cells (HSPCs) into T cells.
Although neither Chen or Ha teach the ranges of the BCL11B expression level in the modified cells is increased 2 to 10-fold in the T cells or progenitor cells compared to the BCL11B expression in corresponding control cells as recited in claim 16, one of ordinary skill in the art would recognize that the level of BCL11B expression level is a result effective variable and that the level of BCL11B expression level would be matter of routine optimization depending on such factors as method of overexpressing the protein in the modified cells.
Neither Chen or Ha explicitly teach the method where the BCL11B expression level in the modified cells is at least that of a control CD34+ or CD34-CD4+CD8+ human thymic T-cell precursor as recited in claim 1, and is silent as to the level of expression of the modified cells compared to control CD34+ or CD34-CD4+CD8+ human thymic T-cell precursors. Similarly, Chen and Ha are silent to whether the modified cells have an increased central memory immunophenotype compared to control cells without the increased BCL11B expression and whether the cells are CD45RO+CD62L+CCR7+ T cells. Neither Chen nor Ha explicitly teach the method where the T cells proliferating from the modified cells have an increased central memory immunophenotype compared to control cells without the increased BCL11B expression as recited in claim 26 and do not teach the method where the T cells with the increased central memory immunophenotype are CD45RO+CD62L+CCR7+ T cells as recited in claim 27.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' generated cells differ, and if so to what extent, from the method and cells of Chen and Ha. The prior art cells are the same or similar because they are modified to overexpress BCL11B by transfecting the mature T cells or HSPCs with a heterologous nucleic acid encoding the gene of interest or by inserting the gene using gene editing technology (Chen, pg. 456-457 section 2.1 and Ha, Fig. 2 and pg. 2504 Col. 1 para. 3). The cited art taken as a whole demonstrates a reasonable probability that method for generating the modified cells and the modified cells resulting therefrom are either identical or sufficiently similar to the claimed method and modified cells that whatever differences exist are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants. Clear evidence that the method for producing the modified cells and resulting modified cells of the Chen or Ha do not possess a critical characteristic that is possessed by the claimed method (for example, that Chen’s or Ha’s modified cells do not have BCL11B expression levels that are at least that of control CD34+ or CD34-CD4+CD8+ human thymic T-cell precursors, do not have an increased central memory immunophenotype compared to control cells without the increased BCL11B expression and are not CD45RO+CD62L+CCR7+ T cells) would advance prosecution.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Aug. 6, 2026 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 112 (a) enablement, Applicant argues that they have amended the claims so that the claim no longer recites “a therapeutically effective amount” and there is no required demonstration of a therapeutic outcome to make the claims enabled (Remarks pg. 7 para. 1). Additionally, Applicant argues that the specification gives substantial direction for practicing each step of the claimed method including incubating modified cells in vitro under conditions sufficient for differentiation and proliferation and provides detail protocols for the BCL11B lentiviral vector construction, transduction of HSPCs and ATO culture conditions (Remarks pg. 7 para. 2). However, these arguments were not found to be persuasive, since the specification does not provide detail protocols for T cell therapy for T cell reconstitution following HSCT. The only guidance provided is that any suitable dose of cells can be administered that promotes T cell reconstitution in a subject with some potential dosages and potential outcomes (see para. 0102 of published application).
Applicant argues that the specification also provides working examples that demonstrate that the claimed process of producing engineered T cells where the BCL11B-overexpressing HSPCs exhibit accelerated T-cell differentiation, increase single-positive T cell output, production of cells having a naïve mature T-cell phenotype, and T cells that exhibit enhanced proliferation and robust differentiation into CCR7+CD62L+CD45RO+ central-memory cells upon activation (Remarks pg. 7-8 bridging para.). Applicant argues that the specification does not need to contain a working example where the invention is otherwise disclosed that a person of ordinary skill in the art can practice it without undue experimentation. Applicant further argues that the ATO system is a recognized model of human thymopoiesis which is relevant to the claims, since the differentiation and production of the engineered T cells occur in vitro prior to administration (Remarks pg. 8 para. 2). However, these arguments were not found to be persuasive, since no evidence has been presented that the generated cells can be used in a generalized method of treating a patient or subject. Even though the ATO system is a recognized model of human thymopoiesis, it does not recapitulate what would happen if the cells are administered to a subject or a model of a HSCT patient. The ATO system does not allow for predicting how the cells will interact with the patient’s immune system, whether they will be toxic, or how long the cells will persist. Additionally, given the unpredictability of T cell therapy, as explained in the rejections under 35 U.S.C §112a, an in vitro model of thymopoiesis does not provide adequate evidence that the cell therapy would be effective in vivo or support that a method of treatment would not require undue experimentation.
Applicant argues that the enhanced properties of the BCL11B-modified cells are intrinsic to the cells; that the specification demonstrates the induction of T-cell associate genes and repression of HSPC- and myeloid-associated genes after transduction of the cells under stroma-free conditions with NOTCH1 ligand and that it is sufficient to initiate T-cell differentiation from HSPCs in organoid lacking NOTCH1 signaling; and supports that BCL11B overexpression directly initiates the T-lineage program in modified cells producing the cell type that mediates thymic reconstitution independently of the environment (Remarks pg. 8 para. 3). However, these arguments were not found to be persuasive, since no evidence has been presented demonstrated that the cells would maintain their enhanced differentiation potential and functional properties once administered to a patient. The instant specification provides no working examples and guidance for a method of a treating a subject with a T cell therapy by administering a therapeutically effective amount of either hematopoietic stem and progenitor cells (HSPCs) or pluripotent stem cells modified to have increased BCL11B expression.
Applicant argues that D’Ippolito and Zhang do not establish that practicing amended claim 1 would require undue experimentation, since D’Ippolito discusses generalized safety consideration for engineered T cells and Zhang discusses challenges involving oncology-directed CAR-T therapies. Applicant further argues that the office action did not explain how these generalized concerns would prevent a skilled artisan from following the disclosed protocol to produce and administer engineered T cells to promote post-HSCT T-cell reconstitution in a subject which is different from tumor targeting immune-therapy (Remarks pg. 8-9 bridging para.). However, these arguments were not found to be persuasive, since both D’Ippolito and Zhang are relevant to T cell therapy or the administration of T cells to a patient and the teachings in both references would apply generally to methods of using T cells for treating conditions or diseases in a patient. Both D’Ippolito and Zhang report the challenges and unpredictability in administering T cells as a therapy in a subject demonstrating the need for detailed guidance and working examples for T cell therapy methods. As stated previously, the specification lacks both detailed guidance and working examples for promoting T cell reconstitution in a HSCT patient by administering the engineered T cells in an amount effective to promote T cell reconstitution.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that characterization of the prior art is overly broad and Themeli is silent with BCL11B and its treatment in leukemia following allogeneic transplantation is not T-cell reconstitution. Applicant further argues that Chen teaches overexpression of BCL11B in already differentiated peripheral T cells not HSPCs or pluripotent stem cells and Valamehr lists BCL11B among numerous genes and does not provide any BCL11B specific experiments or results. Applicant argues that Ha cites cord-blood experiments that show that reducing BCL11B impairs T-cell commitment and Ha’s gain-of-function experiments do not show accelerated production of mature T cells from normal HSPCs, enhanced function or persistence of the resulting T cells, or post-HSCT T cell reconstitution (Remarks pg. 10-11 bridging para.).
However, these argument were not found to be persuasive, for the following reasons. The administration of T cells following HSCT in Themeli would result in T cell reconstitution by expanding the pool of T cells in the patient and Themeli is not being relied upon for the teaching of BCL11B expression in the engineered T cells. Although Chen teaches BCL11B expression in differentiated peripheral T cells this is still relevant to the claimed method, since the cells administered to the patient in the claim are engineered T cells and not HSPCs or pluripotent stem cells. Valamehr is being relied upon for the teaching that T cells derived from iPSCs cells have been modified by introducing genes for expression proteins known to have beneficial characteristics for cell therapy which includes BCL11B. Even though BCL11B is included in a list, Valamehr clearly teaches it is known to improve the T cells for cell therapy when introduced to iPSCs. Ha is being relied upon for teaching further benefits of expressing BCL11B in the HSPCs. It is maintained, that one of ordinary skill in the art would have been motivated to modify the method of Themeli to increase the expression of BCL11B in the hematopoietic stem cells and pluripotent stem cells for the benefit of increasing the proliferation ability and differentiation potential of the cells and to induce T-lineage differentiation as taught by Chen, Valamehr and Ha. In response to applicant's argument that the references do not show accelerated production of mature T cells from normal HSPCs, enhanced function or persistence of the resulting T cells, or post-HSCT T cell reconstitution, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, the references teach enhanced function of the T cells. For example, Chen teaches the overexpression of BCL11B in the cells resulted in increased proliferation ability of the T cells (abstract).
Additionally, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Themeli is being relied upon for the teaching of treating a HSCT patient with engineered T cells that have enhanced function and persistence, and the teaching of BCL11B overexpression in the engineered T cells is taught by Chen, Valamehr, and Ha. One of ordinary skill in the art would have been motivated to modify the method of Themeli to increase the expression of BCL11B in the hematopoietic stem cells and pluripotent stem cells for the benefit of increasing the proliferation ability and differentiation potential of the cells and to induce T-lineage differentiation as taught by Chen, Valamehr and Ha. Applicant addressed each prior art reference separately and only with regard to the specific limitations of that reference. However, when the prior art references are taken as a whole, they teach that the skilled artisan knows each step of the method as currently claimed.
Applicant argues that the Office’s rationale depends on BCL11B’s role in T-lineage commitment as proof that its overexpression in multipotent progenitor cells would produce the claimed results and that prior BCL11B overexpression in murine HSPCs caused cell death (Remarks pg. 11 para. 2). However, this argument was not found to be persuasive, since as stated in the rejection, increasing BCL11B expression was known to improve the ex vivo expansion of cells of hematopoietic stem cells and pluripotent stem cells and the differentiation into T cells and increased BCL11B expression was known to improve proliferation and differentiation of the cells as taught by Chen, Valamehr and Ha.
Applicant argues that the instant application shows that BCL11B expression in human HSPCs have the unexpected benefit of accelerating T cell differentiation and significantly increases mature single-positive T cell output which is not taught by the cited references (Remarks pg. 11 para. 2). Applicant further argues because of this, the Office relied on impermissible hindsight to arrive at the claimed invention (Remarks pg. 11 para. 2). As stated previously, in response to applicant's argument that the references do not show accelerating T cell differentiation and significantly increases mature single-positive T cell output, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, the references teach enhanced function of the T cells. For example, Chen teaches the overexpression of BCL11B in the cells resulted in increased proliferation ability of the T cells (abstract). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
No claims are 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
