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
Pursuant to a preliminary amendment filed on December 23, 2024, claims 1 – 3, 5 – 6, 10 – 11, 16, 20, 23 – 25, 29 – 30, 35, 37, 39, 41, 43, and 46 are currently pending in the instant application. Claims 1, 2, and 3 are independent claims.
Therefore, claims 1 – 3, 5 – 6, 10 – 11, 16, 20, 23 – 25, 29 – 30, 35, 37, 39, 41, 43, and 46 are examined on the merits to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on December 23, 2024, January 17, 2025, August 22, 2025, January 21, 2026, and February 18, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed June 21, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/IB2022/062711, filed December 23, 2022, which claims the benefit of AU2021904222, filed December 23, 2021.
Therefore, the earliest priority date is December 23, 2021.
Claim Objections
Claim 2 is objected to for the recitation of “ii)” in lines 1 – 2. There is a comma missing before the “ii)” in line 2.
Claims 1 and 6 are objected to because abbreviations such as MAGIG , IBMTR should be spell out at the first encounter in the claims. Appropriate correction is requested.
Nonstatutory 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.
The instant claims 1 – 3, 5 – 6, 10 – 11, 16, 20, 23 – 25, 29 – 30, 35, 37, 39, 41, 43, and 46 are provisionally rejected on the grounds of nonstatutory double patenting of the claim of copending Application No. 17,904,581 (US 20230097931 A1, published March 30, 2023). Although the conflicting claims are not identical, they are not patentably distinct from each other because instant application claims 1 – 3, 5 – 6, 10 – 11, 16, 20, 23 – 25, 29 – 30, 35, 37, 39, 41, 43, and 46 are anticipated by claims 1 – 26 of the copending application. This is a provisional nonstatutory double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1 – 26 of the copending application are directed to a method of treating or preventing chronic Graft versus Host Disease (cGvHD) in a human subject in need thereof, the method comprising administering to the subject a composition comprising culture expanded mesenchymal lineage precursor or stem cells (MLPSCs) at a dose of about 1 X 10⁶ MLPSCs/kg to about 3 X 10⁶ MLPSCs/kg, wherein the culture expanded MLPSCs have been cryopreserved and thawed (reads on instant claims 1 – 3). Claim 10 of the copending application teaches that the subject has at least a partial response after 28 days of treatment (reads on instant claim 16). Claim 24 teaches that the composition further comprises Plasma-Lyte A, dimethyl sulfoxide (DMSO), human serum albumin (HSA) (reads on instant claim 37).
The instant application teaches a method of treating GvHD, the method comprising administering a composition of MLPSC, wherein the subject has severe GvHD as determined by MAP. The copending application teaches a method of treating GvHD, comprising administering MPLSCs, while the instant application teaches a method of treating GvHD, comprising administering MLPSCs, wherein the subject has severe GvHD as determined by MAP. The instant application narrows the scope of the subjects that are being treated. Therefore, the instant application is in essence a “species” of the generic invention of copending application. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejection - 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 2– 3, 5 – 6, 11, 16, 20, 23 – 25, 30, 35, 37, 39, and 46 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.
Claims 2, 3, 20, 23, 24 , 25 are indefinite for the recitation of “preferably,” such as recited in claim 2, line 4. It is unclear what are the requirements for treatment, and thus the metes and bounds of the claim cannot be determined.
Claim 5 and 25 are indefinite for the recitation of “the subject’s MAP,” such as recited in claim 5 lines 1 – 2. There is a lack of antecedent basis for the term “the subject’s MAP.”
Claim 6 is indefinite for the recitation of “the IBMTR severity scale” and “the Glucksberg severity scale” in lines 7 – 8. There is a lack of antecedent basis for the terms “the IBMTR severity scale” and “the Glucksberg severity scale.” Claim 6 is also indefinite for the recitation of “Minnesota high risk GvHD” in line 10. It is unclear what is meant by “Minnesota high risk GvHD,” as this term has not been defined in the as-Filed Specification.
Claim 6 is indefinite for the recitation of “and/or” in line 5. It is unclear what the metes and bounds of the term “and/or” could be interpreted in line 6. Specifically, it is unclear what the requirements of the subject with GvHD.
Claim 11 is indefinite for the recitation of “the subject’s GvHD” in line 2. There is a lack of antecedent basis for the term “the subject’s GvHD.”
Claim 20 is indefinite for the recitation of “and/or” in line 3. It is unclear what the metes and bounds of the term “and/or” could be interpreted in line 3. Specifically, it is unclear what the requirements of the treatment with GvHD.
Claim 25 is indefinite for the recitation of “and/or” in line 4. It is unclear what the metes and bounds of the term “and/or” could be interpreted in line 4. Specifically, it is unclear what the requirements of the treatment pertaining to MAP are.
Claim 30 is indefinite for the recitation of “and/or” in line 6. It is unclear what the metes and bounds of the term “and/or” could be interpreted in line 6. Specifically, it is unclear what the requirements of the MLPSC are.
Claim 30 is indefinite for the recitation of “the MLPSCs are culture expanded” in line 4. It is unclear what is meant by the term “culture expanded,” and the cells can be cultured, then expanded, or cultured, or expanded. Thus, the metes and bounds of the claim cannot be determined.
Claim 35 is indefinite for the recitation of “administering between 1x107 cells and 2x108 cells” in line 2. Cells are administered in vivo at a concentration/kg. Thus, it is unclear what concentration of the cells are administered.
Claim 37 contains the trademark/trade name Plasma-Lyte A. Where a trademark or trade name (research designation) is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b). Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the components of the composition, and, accordingly, the identification/descriptions are indefinite.
Claim 37 is indefinite for the recitation of “Plasma-Lyte A (70%), DMSO (10%), HAS (25%) solution” in line 2. It is unclear whether the parenthesis refers to the concentration of the reagent or the amount of the reagent in the composition. Additionally, if the parentheses are referring the amount of the reagent, the total amount is adding up to more than 100%. Thus, the metes and bounds of the claim cannot be determined.
Claim 39 is indefinite for the recitation of “the composition comprises MPC” in line 1 – 3. It is unclear whether MPCs and MLPSCs (as taught in claim 1) are the same. Thus, the metes and bounds of the claim cannot be determined.
Claim 46 is indefinite for the recitation of “and/or” in line 6. It is unclear what the metes and bounds of the term “and/or” could be interpreted in line 6. Specifically, it is unclear what the requirements of the dosing are.
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 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 1- 3, 5, 6, 10 – 11, 20, 23, 25, 29 – 30, and 41 are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Kasikis et al. (hereinafter referred to as “Kasikis”) (Kasikis S. Bone Marrow Transplant. 2021 Nov;56(11):2869-2870. doi: 10.1038/s41409-021-01442-3. Epub 2021 Sep 1. PMID: 34471240; PMCID: PMC9840529.).
Regarding claims 1 - 3, Kasikis teaches using Remestemcel-L as a treatment for graft-vs-host disease (GVHD), wherein the Remestemcel-L is comprised of culture expanded mesenchymal stromal cell (pg. 1). Kasikis teaches that the patients had severe, high risk clinical disease at the initiation of remestemcel-L treatment according to MAP (pg. 2, second paragraph) (interpreted as the subject has severe GvHD as determined by MAP, and having determined a subject’s MAP). (Please note: the as-Filed Specification teaches that mesenchymal lineage precursor or stem cell (MLPSC) refers to undifferentiated multipotent cells that have the capacity to self-renew while maintaining multipotency and the capacity to differentiate into a number of cell types either of mesenchymal origin, for example stromal cells (Paragraph [0115])). Kasikis teaches that 54 children with steroid-refractory (SR) GVHD treated with remestemcel-L as second-line therapy (pg. 1) (interpreted as administering a composition comprising MLPSC to a subject with GvHD, and selecting a subject having MAP indicative of severe GvHD). Kasikis teaches that MAGIC Algorithm Probability (MAP) combines the serum concentrations of two biomarkers, Reg3α and ST2, into a single value that predicts long term outcomes such as response to therapy after 28 days and 6 month non-relapse mortality (NRM) (pg. 2, third paragraph) (interpreted as the morality is 6 month NRM).
Regarding claim 5, Kasikis teaches that remestemcel-L study patients were high risk by MAP ≥0.291 (pg. 2, third paragraph).
Regarding claim 6, Kasikis teaches that 54 children with steroid-refractory (SR) GVHD treated with remestemcel-L as second-line therapy (pg. 1) (interpreted as the subject is a pediatric subject).
Regarding claim 10, Kasikis teaches MAPs ≥0.291 predict high NRM and poor responses to therapy in SR acute GVHD (pg. 2, third paragraph) (interpreted as the subject has a 6 month NRM of greater than 70%).
Regarding claim 11, Kasikis teaches that all 52 of these patients in both groups had GVHD that had either worsened within 3 days, not responded within 7 days, or progressed after an initial response to treatment with systemic steroids (pg. 2, first paragraph).
Regarding claim 20, Kasikis teaches that 1/10 high risk patients treated with BAT were alive compared to 7/11 receiving remestemcel-L at day 180 (Figure 1) (interpreted as the treatment incrases the probability of the subject surviving at least 180 days).
Regarding claim 23, Kasikis teaches that second line treatments in the control group were determined by the treating physician and included extracorporeal photopheresis, etanercept, infliximab, ruxolitinib, anti-thymocyte globulin, mycophenolate, alemtuzumab, basiliximab and tocilizumab (pg. 2, second paragraph).
Regarding claim 25, Kasikis teaches that 8/12 study patients treated with remestemcel-L, who were high risk by biomarkers, achieved a clinical response by day 28 of remestemcel-L (pg. 2, third paragraph) (interpreted as the treatment decreases the subject’s MAP by day 28).
Regarding claim 29, Kasikis teaches that serum concentrations of Reg3α and ST2 was measured by ELISA and calculated the MAP for all 52 patients (pg. 2, third paragraph).
Regarding claim 30, Kasikis teaches using Remestemcel-L as a treatment for graft-vs-host disease (GVHD), wherein the Remestemcel-L is comprised of culture expanded mesenchymal stromal cell (pg. 1).
Regarding claim 41, Kasikis teachs that the patients progressed after an initial response to treatment with systemic steroids (pg. 2, second paragraph).
Kasikis meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Claim Rejection - 35 USC § 103
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.
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 1, 16, 24, 35, 37, 39, 43, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Kasikis, as evidenced by Kurtzberg et al. (Kurtzberg et al. Biol Blood Marrow Transplant. 2020 May;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018. Epub 2020 Feb 1. PMID: 32018062; PMCID: PMC8322819.), and Karantalis et al (Karantalis V. et al. Circ Res. 2015 Apr 10;116(8):1413-30. doi: 10.1161/CIRCRESAHA.116.303614. PMID: 25858066; PMCID: PMC4429294.).
Regarding claim 1, Kasikis teaches using Remestemcel-L as a treatment for graft-vs-host disease (GVHD), wherein the Remestemcel-L is comprised of culture expanded mesenchymal stromal cell (pg. 1). Kasikis teaches that the patients had severe, high risk clinical disease at the initiation of remestemcel-L treatment according to MAP (pg. 2, second paragraph) (interpreted as the subject has severe GvHD as determined by MAP, and having determined a subject’s MAP). (Please note: the as-Filed Specification teaches that mesenchymal lineage precursor or stem cell (MLPSC) refers to undifferentiated multipotent cells that have the capacity to self-renew while maintaining multipotency and the capacity to differentiate into a number of cell types either of mesenchymal origin, for example stromal cells (Paragraph [0115])). Kasikis teaches that 54 children with steroid-refractory (SR) GVHD treated with remestemcel-L as second-line therapy (pg. 1) (interpreted as administering a composition comprising MLPSC to a subject with GvHD, and selecting a subject having MAP indicative of severe GvHD). Kasikis teaches that MAGIC Algorithm Probability (MAP) combines the serum concentrations of two biomarkers, Reg3α and ST2, into a single value that predicts long term outcomes such as response to therapy after 28 days and 6 month non-relapse mortality (NRM) (pg. 2, third paragraph) (interpreted as the morality is 6 month NRM).
Kasikis does not specifically exemplify the partial response after 28 to 180 days of treatment (claim 16), the reduction of the subject’s ST2 levels (claim 24).
Regarding claim 16, Kasikis teaches that the MSCs reduced damage in target organs, including wound healing properties in the GI tract (pg. 3, third paragraph). Thus, this can be interpreted as a reduction of the gastrointestinal tract score of at least one point.
Regarding claim 24, Kasikis teaches Figure 1, which teaches the MAP scores at day 180 after treatment with remestemcel-L. The initial MAP score for all patients was 0.29, and for many patients, it has dropped below 0.29. The MAGIC Algorithm Probability (MAP) combines the serum concentrations of two biomarkers, Reg3α and ST2 (pg. 2, second paragraph). Since the MAP score have dropped, the ST2 scores are considered to be lowered as well.
Regarding claim 35, 37, 43, and 46, Kasikis teaches the teachings of the phase 3 (NCT02336230) clinical study, but does not specifically exemplify the dosage and components of the administered composition. Kurtzberg also reports the teachings of the phase 3 (NCT02336230) clinical study and the components of the administered composition. Regarding claims 35, 43, and 46, the children with primary SR-aGVHD were treated intravenously with 2 × 106 cells/kg twice weekly for 4 weeks, as evidenced by Kurtzberg t al. (Abstract). Regarding claim 37, Remestemcel-L comprises healthy adult volunteer donor human bone marrow-derived MSCs that have been ex vivo cultured and cryopreserved in Plasma-Lyte A supplemented with human serum albumin and dimethyl sulfoxide, as evidenced by Kurtzberg et al. (pg. 4, third paragraph).
Regarding claim 39, Kasikis teaches the use of mesenchymal stromal cell, but does not specifically exemplify that the cells are isolated from bone mononuclear cells with anti-STRO-3 antibodies. However, it is well known in the art that MPCs as by selecting cells bearing the Stro-1 or Stro-3 receptor from bone marrow and then culture expanding that cell, as evidenced by Karantalis et al. (pg. 3, first paragraph).
Conclusion
Claims 1 – 3, 5 – 6, 10 – 11, 16, 20, 23 – 25, 29 – 30, 35, 37, 39, 41, 43, and 46 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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