DETAILED ACTION
This action is in reply to papers filed 02/17/2026.
Claims 1, 3-4, 10-13, 15-16, and 19-29 are pending and examined herein.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/17/2026 has been entered.
Withdrawn Objection(s) and Rejection(s)
The objection to claim 1 regarding minor informalities is withdrawn in light of the amendment to the claim to strike the limitation comprising the term “TNFR1.”
The rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn in light of the amendment to the claim to recite “in vitro” at line 6.
Applicant’s arguments regarding rejections under 35 U.S.C. 103 are addressed following the rejections.
Claim Objections
Claims 12-13 and 25 are objected to because of the following informalities:
Claims 12-13: Occurrences of the phrase “- Reduction in” should be corrected to “reduction in” (i.e., the dash should be removed and the limitation should start in the lower, rather than capital, case).
Claim 25: The percentages of the composition, which currently follows each component in parentheticals, should be rewritten such that they precede the component without parentheticals (e.g., “DMSO (10%)” should be rewritten as “10% DMSO”).
Appropriate correction is required.
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.
Claim(s) 1, 3-4, 10-13, 15-16, and 19-29 are rejected under 35 U.S.C. 103 as being unpatentable over Sturm (US 2015/0307844 A1; cited in IDS dated 11/20/2024 as US69), in view of Itescu (WO/2018/202853; cited in IDS dated 11/20/2024 as FP19).
Sturm discloses the production of mesenchymal stromal cells (MSCs; reads on mesenchymal stem cells; claims 1 and 15) and their use for the treatment of chronic Graft versus Host Disease in a human subject (p 9, Example 3).
Sturm discloses manufacturing MSCs (p 9, Example 1) derived from bone marrow mononuclear cells (para 139), wherein the MSCs were culture expanded for up to 5 passages (para 140; claims 1, 4), then cryopreserved in 10% DMSO, 50% Plasma-Lyte (reads on sterile, non-pyrogenic isotonic solution), 20% sodium chloride, and 20% human serum albumin and stored at -196℃ (para 140; claims 1, 24). Cells were prepared to allow for doses of 1-10 x 106 cells/kg patient body weight (para 140; claim 1).
Sturm further discloses using the MSCs produced by the method of Example 1 to treat steroid-refractory chronic graft versus host disease (cGVHD) (Example 3; claim 1). Patients with cGVHD had extensive disease despite prednisolone (reads on steroid immunosuppressant of claim 1 (ii); para 148) and had major target organ(s) with a score of 2 or greater according to the NIH Consensus Criteria (para 148). Patients received MSCs from family members or doners (para 156; claim 16). Patients received 8 infusions of MSC twice weekly for 4 weeks intravenously, or 2 infusions at weekly intervals (para 153; claims 1, 19-20). Most patients with cGVHD received 2 infusions in 1 treatment episode (para 157).
Two patients with cGVHD achieved a complete response, and two patients achieved a partial response (para 159; Table 2; claim 1 (iii)). Complete response was defined as loss all symptoms and signs of cGVHD, and partial response was an improvement in the NIH consensus score of at least one (para 149). Complete response was characterized in loss of oral and skin symptoms (p 11, Table 2), and partial response was characterized in reduction in KCS scores (keratoconjunctivitis sicca; reads on eye score), mucositis score (reads on gastrointestinal tract score), and skin score (Table 2) (claims 12-13).
Patients with complete and/or partial response received between 2 to 8 infusions (Table 2; claims 19- 20). Based on the administration regime used in the experiment (supra), a patient who received 8 infusions and achieved a complete and/or partial response will have achieved said response 28 days after initiation of treatment (claims 1 (iii), 10). Sturm discloses that 100% of patients with cGVHD who showed a partial or complete response was alive at least 5 months after the first MSC infusion (Figure 2B), implying that these patients had achieved partial or complete responses 90 days after initiation of treatment (claims 1 (iii), 11).
Regarding limitation (i) in claim 1: Sturm is silent as to the effect of the MSCs on IL-2Rα expression on T cells.
Itescu teaches an experiment to assess the immunosuppressive potential of the MLPSCs described above, by using an in vitro T cell proliferation assay as measured by percent inhibition of IL-2R (para 384, Fig 2). Itescu teaches that immunoselected MLPSCs have greater inhibition of IL-2R expression compared to MLPSCs produced under previous manufacturing conditions (para 384, Fig 2). Immunoselected MLPSCs exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells (MLPSCs A and B) (Fig 2). Itescu teaches that inhibition of T cell IL-2Ra expression greater than 65% in vitro is indicative of biological activity or therapeutic efficacy of the MLPSCs (para 31).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Sturm by utilizing immunoselected MLPSCs, as taught in Itescu. One of ordinary skill in the art would have been motivated to make this modification because Itescu teaches that immunoselected MLPSCs exhibit greater than 65% inhibition of IL-2R expression on T cells, which indicate improved therapeutic efficacy of the MLPSCs. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Itescu teaches a method of producing MLPSCs comprising immunoselection, which can then be used for the treatment or prevention of GVHD.
Regarding claim 3: Following the discussion of claim 1, Sturm is silent as to whether the MSCs used in the composition to treat patients with cGVHD in Example 3 were culture expanded from an intermediate cryopreserved MSC population.
However, Sturm teaches that once the MSCs have been expanded, they may be cryopreserved for future use, including subculturing upon thawing (para 108; reads on cells intended to be culture expanded from an intermediate cryopreserved MSC population).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have carried out the treatment disclosed in Example 2 of Sturm by using MSCs culture expanded from a cryopreserved MSC population, as taught in Sturm, to preserve and obtain an appropriate number of donor cells for patient treatment. One of ordinary skill in the art would have a reasonable expectation of successfully using an intermediate population of cryopreserved MSCs in the treatment regimen because Sturm teaches that MSCs can be cryopreserved for subculturing.
Regarding claims 21-23: Following the discussion of claim 1, Sturm teaches administering MSCs to treat cGVHD, wherein the patient receives at least 2 to 8 doses.
Sturm does not teach the limitations wherein the first two doses are administered weekly for two weeks (claim 21), the first doses are administered once weekly every two weeks (claim 22; see Claim Interpretation), or third and subsequent doses are administered monthly (claim 23).
However, Sturm teaches that “The cells may be given as a single dose, multiple doses over defined time period, or up to and including routine chronic maintenance dosing. The doses of cells will typically be spaced apart. For example, the doses might be 1 to 2 days apart or weekly or monthly” (para 132). Sturm further teaches that the patient may receive between 1 to 20, or more, doses (para 131).
Itescu teaches that “Selecting an administration regimen for a therapeutic formulation depends on several factors, including the serum or tissue turnover rate of the entity, the level of symptoms, and the immunogenicity of the entity. Preferably, an administration regimen maximizes the amount of therapeutic compound delivered to the patient consistent with an acceptable level of side effects” (para 277).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the administration regimen disclosed in Sturm to maximize the amount of therapeutic compound delivered to the patient consistent with an acceptable level of side effects, as taught by Itescu, to increase treatment efficacy and safety. One of ordinary skill in the art would have had a reasonable expectation of successfully modifying the timing of doses administered to patients to arrive at the claimed invention because Sturm teaches that the cells may be administered as multiple doses over a defined time period, including weekly and monthly.
Regarding claim 25: Following the discussion of claim 1, Sturm teaches cryopreserving MSCs in 10% DMSO, 50% Plasma-Lyte, and 20% human serum albumin (HSA). In an alternate embodiment, Sturm teaches that the isotonic solution for intravenous use comprises about 2% HSA (para 106).
Sturm does not teach a composition comprising 70% Plasma-Lyte or 5% HSA.
However, Sturm teaches that a cell therapy composition comprises “cells in the appropriate suspension medium at the appropriate cell number for therapy” (para 105). Sturm further teaches that “The "appropriate suspension medium" will depend upon the therapy, route of administration, cell type and the like” (para 106), and that “The techniques for preparing the cells of the invention for cryopreservation will depend upon the end use for the cells” (para 108).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have determined the optimal percentage of Plasma-Lyte and HSA in the composition of claim 1, as taught by Sturm, to obtain an appropriate suspension medium most suited for the particular therapy undertaken. One of ordinary skill in the art would have had a reasonable expectation of successfully determining the optimal percentage of individual components in the composition of claim 1 because Sturm teaches that the appropriate suspension medium depends on, and therefore can be adjusted for, factors including the route of administration and cell type. Furthermore, 5% HSA falls within the range of 2% and 20% HSA, as taught in Sturm.
Regarding claim 26: Following the discussion of claim 1, Sturm is silent as to the concentration of viable cells in the composition.
However, Sturm teaches that a cell therapy composition comprises “cells in the appropriate suspension medium at the appropriate cell number for therapy” (para 105). Sturm further teaches that “The "appropriate cell number" [for administration] is again dependent of the therapy being undertaken, route of administration, cell type and the like” (para 107).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have determined the optimal number and density of cells in the composition of claim 1, as taught by Sturm, to obtain a cell therapy composition most suited for the particular therapy undertaken. One of ordinary skill in the art would have had a reasonable expectation of successfully determining the optimal number and density of cells in the composition of claim 1 because Sturm teaches that appropriate number of cells in the composition depends on, and therefore can be adjusted for, factors including the route of administration and cell type.
Regarding claims 27-29: Following the discussion of claim 1, Sturm teaches manufacturing MLPSCs in a first culture medium, comprising 10% fetal bovine serum, and subsequently in a second culture medium comprising 2% human serum albumin (Example 1, para 139-141). Sturm does not teach expanding the MLPSCs in a single type of serum.
Itescu teaches a method of culturing immunoselected MLPSCs, wherein the MLPSCs are expanded in a single MLPSC expansion medium comprising 20% fetal bovine serum (para 302, 348). Itesu teaches that immunoselected MLPSCs cultured according to this method exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells (MLPSCs A and B) (Fig 2). Itescu teaches that inhibition of T cell IL-2Ra expression greater than 65% in vitro is indicative of biological activity or therapeutic efficacy of the MLPSCs (para 31).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Sturm by utilizing immunoselected MLPSCs cultured in a single MLPSC expansion medium comprising 20% (v/v) fetal bovine serum, as taught Itescu. One of ordinary skill in the art would have been motivated to make this modification because Itescu teaches that culturing immunoselected MLPSCs in an expansion medium comprising 20% fetal bovine serum results in cells that exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Itescu teaches the use of a medium comprising a single type of serum (i.e., fetal bovine serum) at 20% (v/v) to culture immunoselected MLPSCs.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 10-13, 15-16, and 19-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 16, 30, 37, 39, 43 and 46 of copending Application No. 18/723,204 (reference application) in view of Sturm (US 2015/307844 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons: Regarding claim 1 of the instant application, copending claim 1 recites a method for treating GvHD comprising administering a composition comprising MLPSCs. Copending claim 11 recites that the subject is refractory to steroid therapy. Copending claim 30 recites that MLPSCs are culture expanded and cryopreserved (claim 3), are MSCs (claim 15), and are allogenic (claim 16). Copending claim 43 recites that the composition is administered intravenously. Copending 46 recites that the subject received at least 2, 3, 4, 5, 6, 7, 8, 9 or 10 doses, wherein the first two doses are administered weekly for two weeks or are administered weekly every two weeks, and/or third and subsequent doses are administered monthly (claims 19-23). Copending claim 16 recites that the subject has at least a partial response at least 28 to 180 days after treatment (claims 10-11).
The copending claims do not recite the limitation wherein the disease to be treated is chronic GvHD. Sturm teaches the use of mesenchymal stromal cells (MSCs; reads on mesenchymal stem cells) for the treatment of chronic Graft versus Host Disease in a human subject (p 9, Example 3).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have applied the method of treating GvHD recited in the copending claims to treat chronic GvHD. One of ordinary skill in the art would have had a reasonable expectation of successfully applying the method to treat chronic GvHD because Sturm teaches that a composition comprising MSCs can be used for the treatment of chronic GvHD.
Following the discussion above, copending claim 16 reads on claims 12-13; copending claim 37 reads on claims 24-26.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 10-11, 15, 19-20, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22, 25, 28-31, 33-34 of copending Application No. 18/041,303 (reference application), in view of Sturm (US 2015/307844 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons: Regarding claim 1 of the instant application, copending claim 22 recites a method of treating a subject with inflammatory disease by administering a composition comprising MLPSCs that express at least 100 pg/mL TNFR1 into a culture medium. Copending claim 25 recites that the inflammatory disease of claim 22 is GvHD, copending claim 28 recites that the subject is refractory to steroid immunosuppressant and/or a biologic therapy, and copending claim 30 recites that the MLPSCs are culture expanded from a cryopreserved intermediate MLPSC preparation.
Copending claims 22, 25, and 30 do not have the limitation that a) GvHD is chronic GvHD, b) MLPSCs are administered intravenously to a human subject at a dose of about 1x106 MLPSCs/kg to about 3x106 MLPSCs/kg, or c) the subject has at least a partial response 28 to 90 days after treatment.
Regarding limitation a: Sturm teaches the use of mesenchymal stromal cells (MSCs; reads on mesenchymal stem cells) for the treatment of chronic Graft versus Host Disease in a human subject (p 9, Example 3).
Regarding limitation b: Sturm teaches that MSCs were prepared to allow for doses of 1-10 x 106 cells/kg patient body weight (para 140). Strum teaches that patients with cGvHD received infusions of MSC intravenously (para 153).
Regarding limitation c: Patients with complete and/or partial response received between 2 to 8 infusions (Table 2). Based on the administration regime used in the experiment, a patient who received 8 infusions and achieved a complete and/or partial response will have achieved said response 28 days after initiation of treatment (claim 10). Sturm teaches that 100% of patients with cGVHD who showed a partial or complete response was alive at least 5 months after the first MSC infusion (Figure 2B), implying that these patients had achieved partial or complete responses 90 days after initiation of treatment (claim 11).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have applied the method of treating GvHD recited in copending claims 22 and 25 to treat GvHD with the additional limitations of a-c above, to provide therapy to patients with chronic GvHD. One of ordinary skill in the art would have had a reasonable expectation of successfully modifying the method with the additional limitations of a-c because Sturm teaches that a composition comprising MSCs can be administered intravenously to a human subject with chronic GvHD at a dose of about 1x10^6 MLPSCs/kg to about 3x10^6 MLPSCs/kg, which results in the subject having at least a partial response 28 to 90 days after treatment.
Following the discussion above, copending claim 29 reads on instant claims 19-20; copending claim 30 reads on instant claim 3; copending claim 31 reads on instant claim 15; copending claim 33 reads on instant claims 24-25; and copending claim 34 reads on instant claim 26.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
RE: Rejections under 35 U.S.C. 103
Applicant argues: Applicant notes that the teachings of Sturm are focused on, and strongly suggest to a person of ordinary skill in the art, the necessity of particular cell culture conditions to obtain MLPSCs that are suitable for use in human cell therapy. Indeed, the very title of Sturm is "Cell Culture Method," and Sturm emphasizes that "Despite their promise, the clinical results obtained to date with MSC have generally been poor. The major reasons for these poor clinical outcomes appears to be due [to] the way the MSC have been produced." (paragraph [0003]; emphasis added). Thus, there can be little doubt that a person of ordinary skill in the art will view Sturm as teaching that following the specific culture methods taught in this document is critical to obtaining a population of MLPSCs that is suitable for cell therapy.
A key feature of the culture method taught in Sturm is that cells are to be cultured for a period
in a ("second") culture medium comprising human serum prior to cryopreservation or harvesting of cells for use in therapy. See, e.g., paragraphs [0139]-[0141] in Example 1. Sturm also teaches that the use of a second culture medium that comprises human serum (as opposed to bovine serum throughout the culture process) substantially alters the obtained population of human MSC, as reflected in different cell surface marker expression profiles, as shown in Example 2 [paragraph [0142]) of Sturm.
Turning to Itescu, it is clear that the MLPSC culture process uses non-human (bovine) serum
throughout the culture process for obtaining MLPSCs, i.e., the very aspect of MLPSC production that Sturm teaches to be problematic. Applicant notes that the teachings of Itescu indicate that obtaining MLPSCs having increased capacity to inhibit IL-2Ra expression on T cells does not depend specifically on immunoselection, as adherent-selected hMSCs based on an improved manufacturing process (without
immunoselection) were, likewise, shown to exhibit a capacity to inhibit IL-2Ra expression on T cells. See Itescu, Examples 5 and 6, Table 8, and Fig. 7. Thus, Applicant respectfully submits that, for at least this reason, a person of ordinary skill in the art would have no supported rationale or motivation to combine the teachings of Sturm and Itescu as the production methods for obtaining MLPSC populations suitable for human cell therapy are contradictory.
In response: Applicant’s arguments have been fully considered, but are not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Itescu teaches a method of culturing immunoselected MLPSCs, wherein the MLPSCs are expanded in a single MLPSC expansion medium comprising 20% fetal bovine serum (para 302, 348). Itesu teaches that immunoselected MLPSCs cultured according to this method exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells, which is indicative of biological activity or therapeutic efficacy of the MLPSCs (para 31).
Moreover, Examples 5 and 6 of Itescu show alternative manufacturing processes for producing high potency MLPSCs from stem cells isolated using plastic adherence techniques. However, the disclosure of this alternative process does not negate the data taught in Example 2 of Itescu, which shows that immunoselected MLPSCs exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells.
Applicant argues: Above and beyond these contradictory culture method teachings, each of these references highlights the fundamental importance of culture conditions to the specific properties of the final MLPSC population obtained. In particular, Itescu teaches that even relatively small changes to a MLPSC manufacturing process resulted in hMSCs having a consistently greater ability to inhibit the level of IL-2Ra expression in T cells. See, e.g., Itescu at paragraphs [0413]-[0419]. Thus, it is respectfully submitted that given the substantial differences in culture conditions taught in Sturm versus Itescu, a person of ordinary skill in the art could not reasonably infer that the MLPSCs utilized in Sturm "inherently" have the same properties as obtained by the manufacturing/culture process described in Itescu with respect to their ability to inhibit the level of IL-2Ra expression in T cells.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Itescu at paragraphs [0413]-[0419] (Examples 5-6) teach equipment changes, namely the use of syringe trees and tangential flow filtration in place of the Cytomate Cell Processor (Baxter) to wash, transfer, and concentrate cells, have an effect on the immunosuppressive characteristics of MLPSCs (para 415-416). Examples 5-6 do not pertain to the conditions of the culture medium.
Applicant argues: Itescu solely exemplifies the use of MLPSCs in the treatment of acute graft vs host disease (aGvHD). See Itescu, Example 4. Applicant emphasizes that a person of ordinary skill in the art at the filing date was well aware that aGvHD is a disease that is quite distinct from chronic GvHD. For example, chronic GvHD, unlike aGvHD, is characterized by autoimmunity driven primarily by hyperactivated B cell auto-antibody production and fibrosis. In contrast, in aGvHD, B-cell numbers are often low due to treatment or the disease itself, and they are not considered central to the pathology of this condition. Thus, a person of ordinary skill in the art would not view the findings of Itescu with respect to the of MLPSCs on T cell IL-2Ra expression in the context of acute GvHD as a relevant or informative indicator of MLPSC line suitability for treatment of chronic GvHD. It follows that the person of ordinary skill in the art would have no motivation or clear rationale to combine the teachings of Itescu with those of Sturm to arrive at Applicant's claimed method.
In response: Applicant’s arguments have been fully considered, but are not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the primary reference, Sturm, teaches the use of MLPSCs to treat both acute and chronic GvHD in a human subject in need thereof (e.g., Example 3). Moreover, Itesu teaches that immunoselected MLPSCs cultured according to the method taught therein exhibit greater than 65% inhibition of IL-2R expression on T cells, as opposed to non-immunoselected cells, which is indicative of biological activity or therapeutic efficacy of the MLPSCs in preventing or treating graft versus host disease (para 31-33), which includes both chronic and acute graft versus host disease.
RE: Double Patenting Rejections
Applicant argues: Applicant requests that these provisional rejections be held in abeyance until allowable subject matter has been identified.
In response: Applicant’s arguments have been fully considered, but are not persuasive. A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. See MPEP 804 (I)(B)(1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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