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 OFFICE ACTION
This Office Action is in response to the papers filed on 28 October 2025.
CLAIMS UNDER EXAMINATION
Claims 1-7, 11-14, 16 and 18-24 have been examined on their merits.
PRIORITY
Provisional Application, filed on 15 November 2019, is acknowledged. The Provisional Application does not provide support for fibroblasts selected for CD73. Support for this limitation is found in PCT/US2020/060748, filed on 16 November 2020. The earliest priority is 16 November 2020.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW REJECTIONS
The arguments made in the response filed on 17 September 2025 are acknowledged. The claims have been amended to require CD73 selection. New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 7, 13-14, 16 and 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O’Heeron et al. (Interaction of fibroblasts and immune cells for activation and uses thereof. WO2019108756A1 06 June 2019).
O’Heeron teaches a cell therapy comprising fibroblasts ([0007]). The art teaches treating inflammatory conditions, including inflammatory bowel disorders ([0123]).
Example 18B teaches the following method: Patients with GVHD are administered intravenously 20 million fibroblasts derived from dermal sources expressing >80% CD73 ([0356]). Because the art anticipates the claimed method, it would inherently reduce the risk of IBD in said patients.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as a method described in the specification for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004).
Therefore claim 1 is anticipated.
The art teaches the fibroblasts can be transfected with a vector that expresses IL-10, IL-35 ([0120]). Therefore the fibroblasts are capable of expressing IL-10 and IL-35. Claim 7 is included in this rejection.
Because the art anticipates the claimed method it would inherently reduce the risk of Crohn’s disease or ulcerative colitis as recited in claim 13. The art teaches intravenous administration (supra). Therefore claim 14 is included in this rejection. As set forth above, the art teaches intravenous administration. Therefore the cells must be in a liquid media. Claim 16 is included in this rejection. Because the art anticipates the claimed method it would inherently reduce one or more claimed inflammatory cytokines in the subject. Therefore claims 19-20 are included in this rejection. Because the art anticipates the claimed method it would inherently increase one or more claimed inflammatory cytokines in the subject. Therefore claims 21-22 are included in this rejection.
Therefore Applicant’s invention is anticipated as claimed.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 2-6 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over O’Heeron et al.
Claim 1 is anticipated on the grounds set forth above. The teachings of O’Heeron are reiterated.
Regarding claim 2: O’Heeron teaches fibroblasts are treated with one or more particular agents and/or conditions to be able to directly or indirectly treat inflammatory and/or autoimmune processes. The art teaches interferon gamma and/or platelet rich plasma can endow the ability of the fibroblasts to directly or indirectly actively suppress immune responses. Fibroblasts cultured under these conditions are administered into individuals suffering from autoimmune or inflammatory disorders or at risk thereof ([0109]). Therefore the art teaches treating fibroblasts with agents that increase immune modulatory activity.
While the art teaches the claim limitation, it does not do so with sufficient specificity to anticipate the claim.
It would have been obvious to expose the fibroblasts to agents to increase the immune modulatory activity of fibroblasts. One would have been motivated to do so to suppress the immune response in a patient suppering from an inflammatory disorder. One would have had a reasonable expectation of success since O’Heeron teaches fibroblasts treated with the disclosed agents can successfully treat an immune disorder. Therefore claim 2 is rendered obvious. O’Heeron teaches treating with IL-1 to activate fibroblasts
(see claim 5 of O’Heeron). As evidenced by the PG Pub of the specification, IL-1 transiently activates NF-κB ([0012 of PG Pub). Therefore claims 3-5 are included in this rejection.
Regarding claim 6: O’Heeron teaches quantifying the ability of fibroblasts to modulate mixed lymphocyte reaction. Such an assessment of the immunogenicity by mixed lymphocyte reaction may be used to determine whether or not to use a certain population of fibroblasts ([0021] [0100] [0109]). Fibroblasts are utilized in mixed lymphocyte reactions to assess their ability to suppress immune activation. In a specific embodiment, fibroblasts are treated with one or more particular agents and/or conditions to be able to suppress immune responses ([0109]). Fibroblasts cultured under these conditions are administered into individuals suffering from autoimmune or inflammatory disorders ([0109]).
It would have been obvious to use fibroblasts capable of inhibiting a mixed lymphocyte reaction. One would have been motivated to do so since O’Heeron teaches using a mixed lymphocyte reaction to identify fibroblasts able to suppress an immune response. One would do so to treat individuals with an inflammatory disorder. One would have had a reasonable expectation of success since O’Heeron teaches fibroblasts capable of mixed lymphocyte reaction can successfully treat an immune disorder. Therefore claim 6 is included in this rejection.
Regarding claims 23-24: O’Heeron teaches co-administering one or more immunomodulatory agents(s) to an individual ([0125]). The art teaches the immunomodulatory agents may comprise IL-10, IL-35, and n-acetylcysteine (See [0125] [0280]).
It would have been obvious to co-administer IL-10, IL-35, and n-acetylcysteine. One would have been motivated to do so since O’Heeron teaches these immune modulatory agents can be used to suppress an immune response. One would do so to treat a subject with an immune disorder. One would have had a reasonable expectation of success since O’Heeron teaches fibroblasts can be co-administered with these agents.
Therefore claims 23-24 are included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over O’Heeron in view of Kassis et al. (previously cited; Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads. Bone Marrow Transplantation (2006) 37, 967–976).
Claim 1 is rejected on the grounds set forth above. The teachings of O’Heeron are reiterated. O’Heeron teaches fibroblasts can be obtained from the same individual’s body (autologous; [0066] [0086] [0098]).
O’Heeron teaches immune cells can be derived from mobilized peripheral blood produced through pretreatment of an individual with one or more of G-CSF and flt-3 ligand (see [0027 and claims 166-167 of O’Heeron).
The art does not teach obtaining fibroblasts from mobilized peripheral blood as recited in claims 11-12.
Kassis teaches human donor blood can be mobilized using granulocyte colony-stimulating factor (G-CSF) (Abstract). The art teaches fibroblast-like cells can be isolated (page 970, right column, first paragraph). The art teaches the technique used only isolates cells with a fibroblastic phenotype (see page 974, right column, first paragraph).
It would have been obvious to isolate fibroblasts from the peripheral blood of a patient exposed to G-CSF. O’Heeron teaches using autologous fibroblasts and Kassis teaches fibroblast-like cells can be obtained from mobilized donor blood. One would have been motivated to do so to utilize donor blood as a source of fibroblasts. One would have had a reasonable expectation of success since One would have expected similar results since both references are directed to fibroblast cells. Therefore claims 11-12 are rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over O’Heeron in view of Chang et al. (previously presented; Fabrication of pre-determined shape of bone segment with collagen-hydroxyapatite scaffold and autogenous platelet-rich plasma. J Mater Sci: Mater Med 20, 23–31 (2009).
Claim 16 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. O’Heeron administers fibroblasts in a liquid media (supra). O’Heeron teaches fibroblasts can be suspended in PBS for injection ([0323]).
O’Heeron teaches culture in media supplemented with human plasma ([0014]).
The art teaches fibroblasts are cultured ex vivo for preserving viability and proliferative ability. O’Heeron teaches modifying known culture techniques to decrease recognition of fibroblasts by the recipient immune system. Fibroblasts are cultured in conditions that lack xenogeneic components. Fetal calf serum is substituted an agent that facilitates reduction of immunogenicity of fibroblasts, for example, human platelet rich plasma ([0014] [0287]).
The art is silent regarding the use of heat-inactivated plasma as recited in claim 18.
Chang teaches PRP can be prepared by mixing with a sterile saline solution. The art teaches inactivation for injection (2.2 Preparation of platelet-rich plasma, page 25).
It would have been obvious to provide fibroblasts in autologous PRP. One would have been motivated to do so since O’Heeron PRP improves the efficacy of fibroblasts. The skilled artisan would use autologous PRP since O’Heeron teaches excluding xenogenic components to prevent an immune response. The skilled artisan would use inactivated PRP for injection as taught by Chang. One would optimize the amount of PBS based on
the desired concentration of cells to be administered. Therefore claim 18 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653