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 .
This action is responsive to the claim set filed on Nov. 4, 2024. Claims 1-8 are pending and examined below.
Priority
The application is a DIV of U.S. App. Serial No. 16/996,786, which claims priority to provisional application 62/889,438, filed Aug. 20, 2019; as such the earliest possible priority date is Aug. 20, 2019.
Information Disclosure Statement
The information disclosure statement filed Nov. 4, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Claim Rejections - 35 USC § 102/§ 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 (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.
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) 1-8 are rejected under 35 U.S.C 102(a)(1) 35 U.S.C. 103 as being anticipated by, or in the alternative as being unpatentable over, Munir et al. (Stem Cell Dev, 2015) as evidenced by Ulrich et al. (Stem Cells Dev, 2015, cited in IDS filed on Nov. 4, 2024).
The claims are directed to methods of treating a patient having osteoarthris, degenerative disc disease or an autoimmune disease by inhibiting immune responses in the patient through administration of mesenchymal stem cells (MSC) that express CD146 receptors in an amount of at least 10 pg/106 cells.
Munir et al. teach the immodulatory potential of mesenchymal stem cells (MSC) and their therapeutic efficacy in clinical trials of Crohn’s disease, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). (Abstract). Munir teaches that MSC are known to dampen the innate immune response through numerous, independent pathways and concludes, “MSC appear to have the ability to turn off inflammatory response…” (pg. 2092, “MSC and innate immunity”). Munir et al. teach three clinical trials that administered human bone-marrow MSC to patients, specifically NCT 01540292 treating severe or refractory Crohn’s disease; NCT00698191 treating refractory systemic lupus erythematosus; and NCT01873625 treating affected knee osteoarthritis caused by rheumatoid arthritis. (pg. 2094, Table 1).
As evidenced by Ulrich et al., all human bone-marrow MSC express CD146bright, such that trying to separate MSC from this source into functionally different positive and negative subsets used FACS was not possible. (pg. 1563, 2nd col. “In addition, in our recent experiments, all human bmMSC expressed CD146 at a bright signal intensity. We still attempted to separate human bmMSCs in CD146pos or CD146neg subsets by FACS, but functionally different subsets of MSCs were not obtained.”) (citations omitted)”).
Munir et al. is silent as to the concentration of the CD146 receptors in the bone-marrow MSC that were administered. The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not applicants' MSCs that express CD146 receptors in an amount of at least 10 pg/106 cells, differ and if so to what extent, from the prior art’s human bone-marrow MSCs which are known to express CD146bright. Where an examiner cannot determine whether or not the reference inherently possesses properties which anticipate, or render obvious, the claimed invention a rejection under §§102/103 is appropriate. See MPEP §§ 2112-2112.02.
The cited art taken as a whole demonstrates a reasonable probability that the cells administered by Munir et al. and the method of administration is either identical or sufficiently similar to the claimed cells administered for treatment of disease, or that whatever differences exist, they are not patentably significant. Therefore, the burden of establishing novelty or unobviousness by objective evidence is shifted to applicants. See MPEP § 2212(v). Clear evidence that the human bone-marrow MSCs of the cited prior art do not possess a critical characteristic that is possessed by the claimed MSCs that express CD146 receptors in an amount of at least 10 pg/106 cells would advance prosecution. Applicant is requested to specifically point out the support for any amendments made to the disclosure and arguments in response to this Office Action, including the claims. See MPEP §§ 714.02 and 2163.06. Applicant is also requested to refer to pages and line numbers in the as-filed specification. It is noted that other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
As Munir et al. teach three clinical trials that administered human bone-marrow MSC to patients, and all bone-marrow MSC are positive for CD146, it is asserted that the human bone-marrow MSCs administered to treat Crohn’s disease, SLE and RA taught by Munir et al. had MSCs that express CD146 in an amount of at least 10 pg/106 cells.
Even if the human bone-marrow MSCs administered as taught by Munir et al. do not meet the limitation that they express CD146 receptors in an amount of at least 10 pg/106 cells, this difference would have been obvious, as Munir et al. teach that differences seen in clinical application are “likely to be due to differences in the MSC source and experimental conditions, such as the duration of treatment with TLR agonists and the number of MSCs used.” As such, modifying the cells prior to administration is a result-effective variable, and thus, prima facie obvious. MPEP 2144.05.
With respect to claim 2, Munir et al. teach the claimed autoimmune diseases, specifically RA, SLE and Crohn’s disease.
With respect to claim 3 and 8, Munir et al. teach intravenous administration for NCT 01540292 treating severe or refractory Crohn’s disease; NCT00698191 treating refractory systemic lupus erythematosus; and inter-articular administration for NCT01873625 treating affected knee osteoarthritis caused by rheumatoid arthritis. (pg. 2094, Table 1). With respect to claim 8, Munir et al. inherently teaches administration of the bone-marrow MSCs in an acceptable pharmaceutical carrier, as each of these routes of administration – IV or inter-articular – would require the cells be suspended in acceptable pharmaceutical carrier.
With respect to claim 4-6, (each of which increases the amount of CD146 receptors in 106 cells (12, 15, and 18), as Munir et al. teach three clinical trials that administered human bone-marrow MSC to patients, and all bone-marrow MSC are positive for CD146, it is asserted that the human bone-marrow MSCs administered to treat Crohn’s disease, SLE and RA taught by Munir et al. had MSCs that express CD146 in an amount of at least each of these claimed concentrations. If that is not the case, applicants are encouraged to present information to support this assertion, including indicating how the cells that administered are prepared such that the concentration of CD146 receptors is increased.
With respect to claim 7, Munir teaches human mesenchymal stem cells. (pg. 2094, Table 1).
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
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