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 .
Applicant’s amendment and response filed on 5/11/2026 has been received and entered into the case.
Claims 1-21, 23, 26, 32-33 and 35-36 have been canceled, and claims 22, 24-25, 27-31 and 34 have been considered on the merits. All arguments have been considered.
Claim Rejections - 35 USC § 112
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 22, 24-25, 27-31 and 34 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a method of “treating” a subject with GVHD by administering a composition of mesenchymal lineage precursor or stem cells.
The scope of “treating” is broad as the instant specification does not define the term but discloses examples of the term. Paragraph [0047] of the instant specification discloses: “the terms “treating”, “treat” or “treatment” include administering a population of mesenchymal lineage stem or precursor cells and/or progeny thereof and/or soluble factors derived therefrom to thereby reduce or eliminate at least one symptom of a disease disclosed herein.” This statement is not a definition limiting the scope of the term “treating” and thus, the scope of “treating” would encompass any outcome of the method including not only “reducing” at least one symptom of the GVHD. It is noted that “eliminating at least one symptom” would be broadly considered to include “curing”, i.e. eliminating all the symptoms of GVHD. As the claims require a subject with GVHD, the scope of the claimed method does not encompass “preventing” GVHD.
Considering the broad scope of “treating” that encompassing “curing” as discussed above, it is considered that the instant specification failed to provide sufficient written description to support the entire scope of the claimed invention.
The instant specification does not provide any convincing evidence that the claimed method would necessarily and sufficiently cure the GVHD in a subject. The description in the instant specification is prophetic and no actual results to support the claimed method to arrive preventing or curing of any inflammatory disease including T-cell mediated inflammatory disease such as GVHD.
With the prophetic embodiment and limited description in the instant specification, and highly unpredictable nature of the claimed method particularly in preventing and/or curing the GVHD, it is the Examiner’s position that the inventors did not have possession on the entire scope of the claimed “treating” of the GVHD using the claimed mesenchymal precursor or stem cells.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” and further, “The description needed to satisfy the requirements of 35 U.S.C. 112 "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.< Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art. In most technologies which are mature, and wherein the knowledge and level of skill in the art is high, a written description question should not be raised for claims >present in the application when originally filed,< even if the specification discloses only a method of making the invention and the function of the invention. See, e.g., In re Hayes Microcomputer Products, Inc. Patent Litigation, 982 F.2d 1527, 1534-35, 25 USPQ2d 1241, 1246 (Fed. Cir. 1992) ("One skilled in the art would know how to program a microprocessor to perform the necessary steps described in the specification. Thus, an inventor is not required to describe every detail of his invention. An applicant's disclosure obligation varies according to the art to which the invention pertains. Disclosing a microprocessor capable of performing certain functions is sufficient to satisfy the requirement of section 112, first paragraph, when one skilled in the relevant art would understand what is intended and know how to carry it out."). In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
Applicant is advised to amend the method to disclose “reducing at least one symptom of graft versus host disease (GvHD) in a subject in need thereof” instead of “treating a subject with GvHD”.
Claims 22, 24-25, 27-31 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing at least one symptoms of GvHD, does not reasonably provide enablement for curing the GVHD. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 USPQd 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
The instant claims are directed to a method of treating GvHD in a subject comprising administering a composition comprising mesenchymal precursor or stem cells (MLPSCs) to the subject.
As discussed above, the scope of “treating” has been determined to encompass “curing” GVHD.
It is not known in the art that GVHD is a curable condition. There is no known cure of GVHD. Thus, while GVHD can be treated to reduce, improve or ameliorate the symptoms by many known means including stem cell therapy, however, they cannot be successfully cured.
The instant specification does not provide any working example and the disclosure is merely prophetic without providing any evidence that the claimed method would produce the claimed “treating” or any therapeutically effective outcome. Considering the characteristic of the claimed cells possessing anti-inflammatory property as discussed in the instant specification, it is plausible that the claimed cells would provide some improvement in controlling the conditions of GVHD. However, there is no showing in the instant specification such that the claimed cells would be able to cure GVHD.
M.P.E.P. § 2164.03 reads, "The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The 'amount of guidance or direction' refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. V. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) ("In applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required.”).”
The court has recognized that physiological activity is unpredictable. In re Fisher, 166 USPQ 18 (CCPA 1970). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved. In re Fisher, 166 USPQ 18 (CCPA 1970).
It is not to be left up to the skilled artisan to figure out how to make the necessary starting materials and then to figure out how to use them to produce the biological effects as recited in the claims. The courts held that the disclosure of an application shall inform those skilled in the art how to use applicant's claimed invention, not how to find out how to use it for themselves. In re Gardner et al. 166 USPQ 138 (CCPA 1970). For the broad scope of the claims, this specification only teaches what is intended to be done and how it is intended to work, but does not actually teach how to do that which is intended.
Thus, it is highly unpredictable if the claimed method would be able to cure GVHD in the subject. There is no working embodiment and no known data in the art suggesting that cure of GVHD is possible. Thus, there is undue experimentations needed to be carried out to determine if the claimed method would enable a person skilled in the art to successfully cure the GVHD.
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 22, 24-25, 27-31 and 34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 22 discloses the term “the selection method” in lines 4-5. There is no antecedent basis for the “selection method”. It is noted that the claim discloses the MLPSCs “selected for use in treatment of GVHD”, however, there is no “method” disclosed in this context. Applicant is advised to amend the limitation to, for example, “wherein the MLPSCs are selected by a method comprising…”
Claim 22 discloses a wherein clause containing steps (i)-(iii) which is disclosed as a selection method. It is not clear if these steps are required for the claimed method as they are disclosed in the wherein clause and they would be considered as optional. For search purpose, the steps disclosed in the wherein clause of claim 22 are not required for the claimed method of treating.
If these steps are required for the claimed method, applicant is advised to disclose them as active steps, i.e. “A method of treating…, the method comprising (i) culturing …; (ii) determining…; (iii) selecting,… and (iv) administering …”
Claims 22 and 24 disclose the term “at least about”. The term “at least” which requires a number for the lower end, i.e. at the minimum requirement, and the term “about” does not provide clear boundary of the range. Thus, one cannot determine what the minimum number of the claimed range, and thus, it is indefinite by using “at least” and “about” together in defining the range in the claims.
In determining the range encompassed by the term "about", one must consider the context of the term as it is used in the specification and claims of the application. Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir. 2007). In< W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), the court held that a limitation defining the stretch rate of a plastic as "exceeding about 10% per second" is definite because infringement could clearly be assessed through the use of a stopwatch. However, the court held that claims reciting "at least about" were invalid for indefiniteness where there was close prior art and there was nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of specific activity is covered by the term "about." Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991).
Claim 22 discloses “”into the culture medium” in step (ii). It is not clear if the term “into” intends to point out that TNF-R1 is secreted “into” the culture medium. It is understood that TNF-R1 is a receptor which is not secreted from the cells. If so, does that mean the amount of TNF-R1 as claimed is directed only to those secreted but not those inside of the cells? Clarification is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 22, 24-25 and 27-31 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Itescu et al. (WO2018/202853; IDS ref. FP24).
Regarding claims 22 and 25, Itescu et al. teach a method of treating GVHD by administering mesenchymal lineage precursor or stem cells (Abstract; para. 54).
Regarding the newly added wherein clause in claim 22, the wherein clause is considered optional as the steps are not directed to the method of treating rather they limit the product being used by the method. See MPEP2111.04(I). The wherein clause is considered as a product-by-process limitation. The product-by-process limitation only provides a structure to the product. In this case, the wherein clause of claim 22 only provides the structure to the MLPSCs expressing at least 200 pg/ml of TNF-R1 utilized in the claimed method of treating.
Itescu et al. teach the step of determining TNFR1 expression of the population of MLPSCs and an amount of at least about 200 pg/ml or at least 250 pg/ml is indicative of biological activity or therapeutic efficacy (para. 48). This limitation meets claim 22 and 24 with regard to the amount of TNF-R1.
Regarding claim 27, the wherein clause of the claim is directed to the result of the claimed method but does not require any active step to be performed. Thus, the limitation does not provide any weight in determining patentability of the claimed method. Furthermore, as the method taught by Itescu et al. is identical with the claimed method in its steps and materials being used, the results are expected the same.
Regarding claim 28 directed to the subject being refractory to steroid immunosuppressant, Itescu et al. teach that the MLPSCs are administered to the subject after the subject has been determined to be steroid refractory (para. 68).
Regarding claim 29 directed to the at least two doses of the composition being administered to the subject, Itescu et al. teach that the subject may receive two or more doses (para. 56).
Regarding claim 30, Itescu et al. teach that the mesenchymal lineage precursor or stem cells may be cryopreserved prior to administration to a subject (para. 151), and the isolated or enriched mesenchymal lineage precursor or stem cells can be cryopreserved, thawed and subsequently or further expanded ex vivo or in vitro by culture (para. 154). Itescu et al. also teach that the mesenchymal lineage precursor or stem cells are isolated, or isolated and enriched, cryopreserved, thawed and subsequently culture expanded (para. 36).
Regarding claim 31, Itescu et al. teach the mesenchymal lineage precursor or stem cells is a population of mesenchymal stem cells (para. 87).
Thus, the reference anticipates the claimed invention.
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 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.
Claim(s) 22, 24-25, 27-31 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Itescu et al. (supra).
The teachings of Itescu et al. anticipate the subject matter of claims 22, 24-25 and 27-31 as discussed above, and thus, they render the claimed invention obvious.
Regarding the limitation directed to the steps of selection method disclosed in claim 22, the 102 rejection above is based on the interpretation of the wherein clause as optional and a product-by-process limitation.
Assuming arguendo even if the limitation is considered to be required for the claimed method of treating, it would have been obvious to a person skilled in the art to carry out the selecting step based on the amount of TNF-R1. This is because Itescu et al. teach a method steps of determining TNF-R1 expression in MLPSCs (para. 220-223), and Itescu et al. teach the amount of TNF-R1 at least about 200 pg/ml or 250 pg/ml would be considered as therapeutic (para. 48). Thus, one skilled in the art would carry out the steps of determining TNF-R1 express of MLPSCs as taught by Itescu et al., and select the population that has at least about 200 pg/ml or 250 mg/ml of TNF-R1 to use in the method of treating GVHD with a reasonable expectation of success.
It is noted that the step (ii) of claim 22 discloses the amount of TNF-R1 expressed by the cells into the culture medium. If this limitation is considered as the measuring secreted TNF-R1, i.e. soluble TNF-R1, Itescu et al. teach that the step of determining the amount of TNFR1 levels includes soluble TNFR1 (sTNFR1) (para. 220), which would be secreted into the culture medium.
Regarding claim 34, while Itescu et al. teach the dosage of the MLPSCs is 2x106 cells/kg via intravenous injection (par. 402), however, they do not particularly teach the composition or a dose comprising greater than 6.68x106 viable cells/ml.
However, it would have been prima facie obvious to a person skilled in the art to determine optimal dose per injection based on the suitable volume of the injectable composition to achieve the desired outcome of treating GVHD with a reasonable expectation of success. By doing so, one skilled in the art would arrive the claimed dosage of greater than 6.68x106 cells/ml. For example, as 2x106 cells per kg of body weight of a subject are administered per injection, total cell number would be at least 108 cells per a person with 50 kg of body weight. As the injection volume per dose can be adjustable, the volume of 10 ml per injection would be at least 107 cells/ml. As such, the concentration of the cells utilized for the treatment of GVHD or an inflammatory disease would be considered as a result-effective parameter that can be readily modifiable by routine experimentations to arrive the claimed cell concentration.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
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 22, 24-25, 27-31 and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6, 10-11, 16, 20, 37 of copending Application No. 18/723204 (reference application) in view of Itescu et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘204 application disclose a method of treating GVHD in a subject by administering a composition comprising MLPSC.
Regarding the newly added wherein clause in claim 22, it is considered optional because they are directed to the product, i.e. product-by-process, but not for the method of treating as they are not required for the claimed method of treating a subject with GVHD. See MPEP2111.04(I). The product-by-process limitation only provides a structure to the product. In this case, the wherein clause of claim 22 only provides the structure to the MLPSCs expressing at least 200 pg/ml of TNF-R1.
While the claims of the ‘204 application do not teach the limitation, however, Itescu et al. teach the step of determining TNFR1 expression of the population of MLPSCs and an amount of at least about 200 pg/ml or at least 250 pg/ml is indicative of biological activity or therapeutic efficacy (para. 48). It would have been obvious to a person skilled in the art to use the MLPSCs having at least 200 pg/ml of TNFR1 for the method of the ‘204 application as Itescu et al. teach that the MLPSCs having at least 200 pg/ml would be therapeutically effective.
Regarding claim 27, claim 20 of the ‘204 application discloses that the treatment increases the probability of the subject surviving for at least 100 days.
Claim 6 of the ‘204 application discloses that the subject is steroid refractory (RE: claim 28).
Claim 46 of the ‘204 application discloses that the subject receives at least two doses (RE: claim 29).
Claim 30 of the ‘204 application discloses that the MLPSCs have been cryopreserved and culture expanded, and the MLPSCs are mesenchymal stem cells (RE: claims 30-31).
Claim 37 of the ‘204 application discloses the composition further comprising Plasma-Lyte A, DMSO, HAS and buffer (RE: claim 33) and the composition comprises greater than 6.68x106 viable cells/ml (RE: claim 34).
Thus, the claims of the ‘204 application in view of Itescu et al. render the claims of the instant application obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22, 24-25, 27-31 and 33-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 10-13, 15, 24-26 of copending Application No. 17/904581 (reference application) in view of Itescu et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘581 application disclose a method of treating GVHD by administering a composition comprising MLPSCs. As the claims of the ‘581 application disclose the identical method of treating GVHD as claimed in the instant application, the results of the ’581 application’s method are expected the same as the instant application (RE: claim 27).
Regarding the newly added wherein clause in claim 22, it is considered optional because they are directed to the product, i.e. product-by-process, but not for the method of treating as they are not required for the claimed method of treating a subject with GVHD. See MPEP2111.04(I). The product-by-process limitation only provides a structure to the product. In this case, the wherein clause of claim 22 only provides the structure to the MLPSCs expressing at least 200 pg/ml of TNF-R1.
While the claims of the ‘581 application do not teach the limitation, however, Itescu et al. teach the step of determining TNFR1 expression of the population of MLPSCs and an amount of at least about 200 pg/ml or at least 250 pg/ml is indicative of biological activity or therapeutic efficacy (para. 48). It would have been obvious to a person skilled in the art to use the MLPSCs having at least 200 pg/ml of TNFR1 for the method of the ‘581 application as Itescu et al. teach that the MLPSCs having at least 200 pg/ml would be therapeutically effective.
Claim 1 of the ‘581 application discloses that the subject is refractory to a steroid immunosuppressant and/or a biologic therapy (RE: claim 28).
Claim 19 of the ‘581 application teach at least two doses (RE: claim 29).
Claim 1 of the ‘581 application teaches that the MLPSCs have been cryopreserved and culture expanded (RE: claim 30).
Regarding claim 31, claim 15 of the ‘581 application teaches that the MLPSCs are mesenchymal stem cells.
Regarding the other components of the composition (RE: claim 33), the claims of the ‘581 application disclose the identical components.
Regarding the concentration of the viable cells in claim 34 of the instant application, claim 26 of the ‘581 application teaches the identical limitation.
Thus, the claims of the ‘581 application in view of Itescu et al. render the claims of the instant application obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Regarding the 112(a) rejections, applicant's arguments have been fully considered but they are not persuasive. It is noted that the claim rejection has been modified due to the instant amendment limiting the inflammatory disease into GVHD. The claim rejection has addressed the GVHD as a species of inflammatory diseases, and the issue with regard to “prevention” is withdrawn. However, the written description and scope of enablement issues are remained because the “treating” as claimed is interpreted to encompass “cure” of GVHD. Applicant is advised to amend the preamble of claim 22 to, for example, “reducing at least one symptoms of GVHD in a subject” to overcome the rejections.
Regarding claim rejection under 112(b), the claim rejection has been withdrawn but a new claim rejection is presented above.
Regarding the 102 rejection, the claim rejection has interpreted that the wherein clause disclosing steps of selecting a population of MPLSCs based on the expression of TNF-R1 requires only the MPLSCs expressing the claimed concentration of TNF-R1, i.e. at least 200 pg/ml of TNF-R1. Applicant is advised to amend the claim to disclose the steps of preparing (i.e. culturing, determining and selecting) MPLSCs as active steps as suggested in the 112(b) rejection above to overcome the rejection.
Regarding the 103 rejection, the rejection has been modified to address the limitation as amended. It is noted that the 103 rejection above has addressed the steps of making the MPLSCs based on the teaching of Itescu et al.
Applicant argued that Itescu teaches TNF-R1 secretion levels primarily as a characterization marker, subordinate to functional T-cell suppression assays, and does not establish TNF-R1 as independently determinative of clinical outcome. The claims do not disclose such that TNF-R1 as independently determinative of clinical outcome. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding the double patenting rejections, applicant requested that the rejections be held in abeyance. This is not a proper response to the double patenting rejection. Thus, the rejections are maintained.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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