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 .
Priority
This application is a national stage entry of a 35 USC 371 of PCT/KR2022/014100 (filed 09/21/2022), which claims priority to REPUBLIC OF KOREA application 10-2021-0170214 (filed on 12/01/2021).
Claim Status
Claims 1-11 and 13 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 13 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claim 13 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because it is directed to a use of mesenchymal stem cells expressing CD47. The claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e. results in a claim which is not a proper process under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ678 (Bd.App.1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp.131, 149 USPQ 475 (D.D.C.1966).
Claim Rejections - 35 USC § 112
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.
Claim 13 is 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 13 is directed to the use of mesenchymal stem cells expressing CD47. Claim 13 provides for the use of mesenchymal stem cells expressing CD47, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim Rejections - 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 (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 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.
Claims 1-11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Braza et al (Stem Cells, 2016) in view of Deng et al (International journal of clinical and experimental pathology, 2015); evidence1d by Chen et al (Scandinavian journal of immunology, 2023).
Braza et al teaches mesenchymal stem cell (MSC) have immunosuppressive functions and is sufficient to treat asthma by being phagocyted by lung macrophages, which leads to M2 suppression (See, Abstract).
Regarding claims 1-3,6 and 11, Braza et al teaches the use of bone marrow derived mesenchymal stem cells (MSCs) and injecting them to allergy induced asthma mice and testing the efficacy (See, p 1837 Methods, Figure 1). This reads on, a method for treating lung disease, comprising administering to a subject a composition, comprising mesenchymal stem cells… as the active ingredient of claim 1. This reads on, wherein the mesenchymal stem cells are derived from…bone marrow of claim 6. This reads on, wherein the lung disease is…asthma of claim 11.
Braza et al does not disclose that the MSCs express CD47.
Deng et al teaches that CD47 is involved in cellular processes such as proliferation, adhesion, and migration, while also being key in immune and angiogenic response. Deng et al teaches that CD47 expression on cells protects them from phagocytosis and that genetic modification of MSCs with CD47 would enhance stem cell therapies (See, p 10556 col 1 paragraph 2).
Deng et al overexpressed CD47 in bone marrow derived mesenchymal stromal cells (MSC) in vitro with an overexpression vector of CD47 cDNA and cell transfection (See, methods p 10558).
Figure 2 of Deng et al teaches that after transfection, the MSC had a significantly higher expression of CD47 mRNA and protein (See, p10560, Figure 2). Deng et al transplanted by tail vein transfusion of CD47+ MSC and un-transfected MSC to rats with myocardial fibrosis (See, p 10558 col 2 paragraph 2, Table 1, and p10559 methods col 1 paragraph 2). This reads on, administering to a subject a composition comprising mesenchymal stem cells expressing CD47 as an active ingredient of claim 1. This reads on, wherein the mesenchymal stem cells are genetically engineered to increase expression of CD47 of claim 2. This also reads on, wherein the genetically engineered mesenchymal stem cells comprise a recombinant vector into which a gene encoding Cd47 has been introduced of claim 3.
Given that both Braza et al and Deng et al teach administering a composition comprising MSCs to a subject, it would have been prima facie obvious to a person having ordinary skill in the art to substitute the MSCs of Braza et al with the CD47+MSCs of Deng et al for a similar purpose. The use of CD47+MSCs would have predictable results of success evidenced by Deng et al in administering the cells into a subject and teaching that including CD47 expression to the cells improves the efficacy of the MSCs. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Regarding claim 4, following the discussion above, Braza et al nor Deng et al teach the percentage of the population of the mesenchymal stem cells express CD47 in the composition.
However, percentage of CD47+MSCs are considered prima facie obvious, as the instant claim requires 20%-99% of a population. One of ordinary skill in the art would be able isolate and make the composition such that the population of CD47+MSCs to be 20%-99%. As such, the percentage of CD47 expressing MSCs population needed for the limitations would have been a matter of routine optimization (See, MPEP 2144.05).
Regarding claim 5, following the discussion above, mesenchymal stem cells (MSCs) are known in the art to be characterized by their expression of CD markers and lacking CD and HLA-DR markers. This is further evidenced by Chen et al, that teaches that MSCs must be positive for CD73, CD90, and CD105 but negative for CD14 and HLA-DR (See, p2 col 1 paragraph 1).
Regarding claim 7, following the discussion above, Braza et al and Deng et al are silent on the level of immunogenicity of the mesenchymal stem cells; however, it appears that MSCs are known in the art to exhibit reduced immunogenicity. This assertation is evidenced by Chen et al teaching that MSCs possess low immunogenicity due to their low expression of major histocompatibility complex/ human leukocyte antigen (MHC/HLA) class I and lack of MHC/HLA class II, and the active ability to suppress MHC driven immune response (See, p2 col 1 paragraph 2). Therefore, it would be inherent that the MSCs exhibit reduced immunogenicity.
Regarding claim 8, following the discussion above, Braza et al teaches that airway inflammation is a feature of asthma and upon injection with MSCs there is a decrease of airway inflammation that is not maintained upon a secondary asthma induction (See, p 1840 col 2). This reads on, wherein the MSCs reduce the inflammatory response of lung tissues. The MSCs in Braza et al are not known to express CD47, results recited in instant claim 8 do not change the method of claim 1 nor the composition administered; thus the result of the MSCs reduce inflammatory response of lung tissues is inherent by the method, that is rendered obvious by Braza et al in view of Deng et al.
Regarding claim 9, following the discussion above, Braza et al teaches that intravenous MSC transplantation in a mouse asthma model results in MSCs not engrafting in the lung tissue, but are phagocyted by lung macrophages and suppress M2 macrophage phenotype (See, p 1841 and Figure 6). The MSCs in Braza et al are not known to express CD47, the results recited in instant claim 9 do not change the method of claim 1 nor the composition administered; thus the result of the MSCs expressing CD47 decrease M1 macrophages and increase M2 macrophages is inherent by the method, that is rendered obvious by Braza et al in view of Deng et al.
Regarding claim 10, following the discussion above, Braza et al teaches that intravenous MSC transplantation in a mouse asthma model results in MSCs not engrafting in the lung tissue, but are phagocyted by lung macrophages and suppress M2 macrophage phenotype (See, p 1841 and Figure 6). The MSCs in Braza et al are not known to express CD47, the results recited in instant claim 9 do not change the method of claim 1 nor the composition administered; thus the result of the MSCs expressing CD47 reduce the expression of α-smooth muscle actin (α-SMA) and matrix metalloproteinase-13 (MMP-13) is inherent by the method, that is rendered obvious by Braza et al in view of Deng et al.
Regarding claim 13, following the discussion above, Braza et al in view of Deng et al render the method of administering CD47 expressing MSCs to prevent or treat lung disease, therefore this claim is also rendered obvious.
Therefore, claims 1-11 and 13 are rendered obvious by Braza et al in view of Deng et al and evidenced by Chen et al.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
Prosecution Insights