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 .
Election/Restrictions
1. The Election filed 5/29/2026, in response to the Office Action of 4/28/2026, is acknowledged and has been entered. Applicants elected without traverse Group I and the species of an inducible pluripotent stem cell which possesses the marker PDGFr-alpha. Claims 1-20 are pending. Claims 10-16 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions. Claims 7 and 9 are withdrawn as being drawn to non-elected species. Claims 1-6, 8, and 17-20 are currently under prosecution as drawn to the elected species.
Priority
2. Application claims the benefit and priority of provisional application 63/414,823 filed on 10/10/2022. Application has been reviewed and the priority is granted to 63/414,823 and the effective filing date of 10/10/2022.
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.
3. Claims 1-6, 8, and 17-20 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.
4. Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are:
Step (b) recites the administration of tolerogenic regenerative antigen presenting cells, but does not make clear where the tolerogenic regenerative antigen presenting cells come from, are they autologous? from the donor of the islet cells? From a culture?
Step (c) recites T cells that have been exposed to a regenerative cell for a sufficient time period, but does not make clear where the T cells or the regenerative cells came from, are they autologous? From the donor of the islet cells? From a culture?
Step (c) also recites the T cells have been exposed to the regenerative cells for sufficient period of time, which should be a step prior to administration of the cells.
5. Claim 1 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 1 recites: “one or more T cells that have been exposed to a regenerative cell for a sufficient time period to allow said T cells to possess ability to enhance islet engraftment;”. The recitation of “a sufficient time period” is unclear as to what defines the metes and boundaries of the limitation.
For the sake of compact prosecution, the examiner has interpreted the claim to be drawn to the administration of any T cells that have been in contact, either directly or indirectly, for any time period with regenerative cells and leads to enhanced islet cell engraftment.
Examiner suggests amending the claim to include steps of isolating or obtaining tolerogenic regenerative antigen presenting cells, T cells, and regenerative cells and a step of the T cells being exposed to the regenerative cells with clearly defined time period for exposure that allows for enhanced islet cell engraftment.
6. Claim 18 recites the limitation "said monocytes" in line 1. Claim 18 depends from claim 1 which does not recite a monocyte. There is insufficient antecedent basis for this limitation in the claim. Examiner suggests amending the claim to depend from claim 17.
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.
7. Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Adv. Sci., 2021, 8:2003708) in view of Svahn (WO2019/158712, pub. 8/22/2019).
Wang teaches a method of increasing efficacy of an islet cell transplant for treatment of diabetes comprising treating a diabetic patient by co-administration of immunomodulatory cells including mesenchymal stem cells (MSC) and tolerogenic dendritic cells along with the administration of the islet cell engraftment. (See Wang, pgs. 11-13, Section 2.3).
Wang does not teach the administration of T cells exposed to a regenerative cell for a sufficient time period to allow T cells to possess ability to enhance islet cell engraftment.
Wang does teach that administration of MSC has had limited acute immunoregulatory effect- including the reduction of the TH1/TH2 ratio, naïve T cells and memory T cells, on delaying islet cell engraftment rejection but not longer than 100 days. (See Wang, pg. 12, section 2.3.1 paragraphs 2-3). Wang also teaches that the allograft rejection mechanism in the fourth phase occurring in the days to months after administration of the transplanted cells is the most destructive phase of allograft rejection and is caused by activated T cells. (See Wang, pgs. 3-4 also Fig. 2 copied below).
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Svahn teaches the use of MSCs in treating autoimmune and transplant rejection, including type I diabetes and islet cells transplantation rejection. (See Svahn, pg. 25 lines 21and 32). In particular, Svahn teaches the use of MSCs in being cultured with immune cells, including T lymphocytes, and contacting them through cell to cell contact or sharing of conditional media.
Svahn does not teach the administration of T cells after being exposed to a regenerative cell for a sufficient time period to allow T cells to possess ability to enhance islet cell engraftment.
Svahn, however, suggests that the immune cell population co-cultured with MSCs could be useful in therapy. (See Svahn, pg. 33 line 23- pg. 34 line 5).
Regarding claims 3-4, Svahn further teaches MSCs can be derived from Wharton’s jelly, bone marrow, peripheral blood, adipose tissue, amniotic fluid, cord blood, and amniotic membrane. (See Svahn, pg. 6 lines 10-30) and express the cell surface markers of CD73, CD90, and CD105.
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to try to improve the method of co-administration of immunomodulatory cells and tolerogenic antigen presenting cells along with islet cell transplantation from Wang using the teachings and suggestions of Svahn for the development of the method of the present claimed invention. It would have been obvious because Wang teaches that the administration of MSCs directly with the islet cell transplant has not had success with long term allograft rejection, Wang teaches that the long term allograft rejection of islet cells is due to the T cell response, and Svahn teaches that the immunomodulatory effect of MSCs in vivo can be exerted in an ex vivo manner and suggests these immune cells can then be used for a therapeutic purpose in disorders including islet cell transplant rejection. It would have a reasonable expectation of success because Wang teaches that MSCs have an immunomodulatory effect on T cells including influencing them to an anti-inflammatory state and Svahn teaches the successful use of MSCs to co-culturing immune cells, including T cells, ex vivo. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective filing date to try to improve the method of Wang with the teachings of Svahn to administer T cells cultured with MSCs that allow the T cells to possess ability to enhance islet engraftment with a reasonable expectation of success at preventing long-term islet cell transplant rejection.
8. Claims 3-6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Adv. Sci., 2021, 8:2003708) in view of Svahn (WO2019/158712, pub. 8/22/2019) as applied to claims 1-4 above, and further in view of Riordan (US 2015/0104470 A1, pub. 4/16/2015.
Wang and Svahn teach the limitations of claims 1 and 2 as discussed above.
Wang and Svahn do not teach the MSC is generated from a pluripotent stem cell that is an inducible pluripotent stem cell that expresses the marker PDGFr-alpha.
Riordan teaches methods of treating autoimmune disorders, including type I diabetes (pgs. 3-4 [0021]-[0022]) and rejection of transplanted cells (pg. 8 [0044]), by the use of immunomodulatory cells including MSCs derived from a) Wharton's Jelly; b) bone marrow; c) peripheral blood; d) mobilized peripheral blood; e) endometrium; f) hair follicle; g) deciduous tooth; h) testicle; i) adipose tissue; j) skin; k) amniotic fluid; 1) cord blood; m) omentum; n) muscle; o) amniotic membrane; o) periventricular fluid; and p) perinatal tissue; that express the markers selected from the group consisting of: STRO-1, CD90, CD56, CD73, CD105, CD54, CD106, HLA-I markers, vimentin, ASMA, collagen-1, fibronectin, LFA-3, ICAM-1, PECAM-1, P-selectin, L-selectin, CD49b/CD29, CD49c/CD29, CD49d/CD29, CD61, CD18, CD29, thrombomodulin, telomerase, CD10, CD13, STRO-2, VCAM-1,CD 146, and THY-1; and are generated from a pluripotent stem cell, including an inducible pluripotent stem cell that express the marker PDGFr-alpha. (See Riordan, pg. 5 [0029]-[0032]).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to use the method of Wang and Svahn with the teachings of Riordan of the present claimed invention. It would have been obvious because Riordan is teaching methods for treating the same conditions and a person of ordinary skill in the art would have known they could use the teachings of Riordan to obtain the MSCs used in the method of Wang and Svahn. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to apply the teachings of Riordan to the method of Wang and Svahn with a reasonable expectation of success at obtaining MSCs.
9. Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Adv. Sci., 2021, 8:2003708) in view of Svahn (WO2019/158712, pub. 8/22/2019) as applied to claims 1-4 above, and further in view of Bhatt (Internat’l J of Endocrinology, 2012, 2012:396524) and Thomson (Transplantation, 2009, S9:S86-90).
Wang and Svahn teach the limitations of claim 1 as discussed above.
Wang and Svahn do not teach the tolerogenic cells as being monocytes capable of inducing T regulatory cells that are capable of suppressing rejection of islet cells and dendritic cell maturation.
Bhatt teaches the use of myeloid-derived suppressor cells (MDSCs) in inducing tolerance. MDSCs are a heterogenous group of myeloid cell population that include a monocyte subgroup. (See Bhatt, pg. 4 section 8). Bhatt teaches the co-transplantation of MDSCs with islet allografts induces the generation of T regulatory cells leading to the suppression of rejection of allogenic islet cells. (See Bhatt, pg. 5 column 1, paragraph 2).
Bhatt does not teach the Treg cells are capable of suppressing dendritic cell maturation.
Thomson teaches that within the transplant microenvironment, T regulatory cells can exert reciprocal, inhibitory effects on dendritic cells to inhibit their maturations and enable them to maintain an immature tolerogenic state. (See Thomson, abstract).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective date to combine the method of Wang and Svahn with the teachings of Bhatt and Thomson to produce the method of the claimed invention. It would have been obvious because Bhatt teaches the use of MDSC which include monocytes that induces the presence of T regulatory cells and leads to the suppression of allogenic islet cell rejection and Thomson teaches that T regulatory cells can inhibit dendritic cell maturation to maintain their tolerogenic characteristics which would lead to a reasonable expectation of success at suppressing islet cell rejection. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective date to use the method of Wang and Svahn with the teachings of Bhatt and Thomson with a reasonable expectation of success at treating islet cell transplantation with the present claimed invention.
Conclusion
10. Claims 1-6, 8, and 17-20 are rejected.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
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