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 papers filed 12/01/2025.
Claim 1 has been amended. Claims 37-39 have been newly canceled and claims 60-62 have been newly added.
Claims 1, 7-9, 16, 25, 29, 34-36 and 53-62 are currently pending.
Claims 29, 34-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/01/2023.
Applicant elected Group I (claims 1-9, 16 and 25) and species (iv) 3D culture: spinners, followed by COL(I)/Matrigel.
Claims 1, 7-9, 16, 25 and 53-62 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
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, 7-9, 16, 25, 53, 56 and 58-62 are rejected under 35 U.S.C. 103 as being unpatentable over Mineau-Hanschke (WO 97/15195) in view of Lu et al (Journal of Tissue Engineering and Regenerative Medicine, 2012) and Basu et al (WO 2012/064369-from IDS filed 06/15/2022).
With regard to the terms “cell cluster” and “spheroid”, Applicant's specification has defined these terms to include an organoid (see page 14 paragraphs 53 and 54 of the as filed Specification).
Applicant has not defined the term “self-generated” anywhere in their disclosure and thus the phrase has been broadly interpreted as the simple manner in which certain cell types adhere to each other to generate a cell aggregate or cell cluster. This is not interpreted to include an embodiment wherein a cell scaffold or matrix is excluded from the culture method as was previously cited in the claims.
Regarding claims 1-2, 7-8, 16, 53, 60-62, Mineau-Hanschke teach methods of forming implantable hybrid matrix implants and explants that contain collagen, microspheres and vertebrate cells (Title, abstract). Generally, any type of cells which is capable of attaching to collagen and/or the microspheres and exhibits a desirable property (bioactive) are included, such as, renal cells, endothelial cells, adipocytes (adipose-derived cells) and precursors thereof (progenitors) (bioactive cell populations) and more than one type of cell can be included. The cells may be present as heterogenous populations (page 5 lines 6-21). Culture systems include a 3D culture that start with spinner cultures and followed by a culture in a collagen type I matrix (Example III page 14-17). Collagens used may include any suitable type (e.g. type I-XI) or a mixture of any two or more. While cell lines are not explicitly listed as a source for cells, they are well known in the prior art in tissue engineering and thus an obvious source for use in the Mineau-Hanschke method.
Mineau-Hanschke do not specifically describe using a collagen type I and/or Matrigel for their collagen matrix mixture with a cell mixture of renal and non-renal endothelial cells.
Lu teach methods of culturing renal cells and state that by simply combining mixed renal cells with collagen/Matrigel that a study was able to re-establish an environment that contained cell-cell interactions, cell-matrix interactions, and growth factors to facilitate the formation of renal structures to simulate the overall environment in vivo that fits the renal cells to settle and form tissues. This optimizes the 3D microenvironment and render it possible to simplify the process of tissue-engineering complex organs like the kidney (page 791, column 2 last 6 lines to page 792, column 1, first 5 lines). Collagen and Matrigel are widely used in tissue engineering and developmental biology as scaffolds or 3D culture carriers because of their similarity to natural ECM (extracellular matrix) (page 787, column 1, 3ʳᵈ paragraph).
One of ordinary skill in the art would have been motivated to use a mixture of collagen type I and Matrigel in the method of Mineau-Hanschke that includes renal cell and non-renal cell mixtures because Lu teach that culturing renal cells with this matrix mixture provides the benefits of re-establishing the interactions, growth factors and environment similar to what is found in vivo and facilitates the formation of renal structures in tissue engineering. One of ordinary skill in the art would have had an additional motivation and a reasonable expectation of success because Mineau-Hanschke specifically teach that a mixture of collagen matrices can be used in their method, Matrigel also contains collagen and Lu teach that collagen and Matrigel are widely used in tissue engineering and developmental biology as scaffolds or 3D culture carriers because of their similarity to natural ECM (extracellular matrix).
Regarding claims 1, 7-9, the combined teachings of Mineau-Hanschke and Lu et al render obvious Applicant's invention as described above, but are silent with regard to the type of renal or endothelial cells used in their cell matrix constructs.
Basu '369 teach injectable, therapeutic formulations containing bioactive renal cells in a temperature-sensitive cell-stabilizing biomaterial (page 2 lines 22-27). Suitable renal cell populations include B2, B3 and B4 cell populations that express EPO and are depleted of B1 and B5 cells (page 8 line 31 to page 11 line 2). Bioactive cells included in the formulations include endothelial cells, as well as endothelial cells of the kidney in heterogenous mixtures of renal cells (page 18 line 4, page 29 line 1-page 30 line 2),
including using cell lines and endothelial cells from HUVEC (human vein endothelial cells, non-renal endothelial cells) (pages 100-101 example 14).
One of ordinary skill in the art would have been motivated to use B2, B3 and B4 renal cell populations, including EPO-producing cells, cells depleted of B1 and/or B5 cell populations, including renal endothelial cells or HUVEC endothelial cells in the method of Mineau-Hanschke because Basu '369 indicate that these are suitable cell types to be used in combination with renal and endothelial cells in a cell matrix construct intended for therapeutic implantation. One of ordinary skill in the art would have had a reasonable expectation of success because Mineau-Hanschke teach that generally any type of cells which is capable of attaching to collagen and/or microspheres and exhibits a desirable property (bioactive) are included, such as, renal cells and endothelial cells (bioactive cell populations), and more than one type of cell can be included, (heterogenous populations) (page 5 lines 6-21).
Regarding claim 25, Mineau-Hanschke teach that their matrices may be stored or shipped in growth medium or any other solution prior to implantation to allow the cells to remain viable (injectable) (page 12 lines 23-25).
Regarding claims 56 and 58-59, Mineau-Hanschke teach concentrations for the cells included in their cell clusters (microspheres) (page 22 for example), but do not specifically teach any required ratios or culture times.
With regard to the cell concentrations in the culture composition, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
The selection of specific cell concentrations clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the function of the final cell product would have been affected by these concentrations.
The selection of specific culture times would have also been a matter of routine optimization and experimentation as these times would have affect the final size of the cell clusters (microspheres) as well as their viability.
Therefore, the combined teachings of Mineau-Hanschke, Lu et al and Basu '369 render obvious Applicant's invention as claimed.
Claims 1 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Mineau-Hanschke (WO 97/15195) in view of Lu et al (Journal of Tissue Engineering and Regenerative Medicine, 2012) and Basu et al (WO 2012/064369-from IDS filed 06/15/2022) as applied to claims 1, 7-9, 16, 25, 53, 56 and 58-62 above and further in view of Yokoo et al (US 2010/0095388, hereinafter referred to as ‘Yokoo’-from IDS filed 06/15/2022).
Regarding claims 1 and 54, the combined teachings of Mineau-Hanschke, Lu et al and Basu '369 render obvious Applicant's invention as described above, but do not specifically teach including non-renal mesenchymal stem cells.
Yokoo teach that mesenchymal stem cells are a beneficial cell type for the creation of an erythropoietin-producing organoid (page 1 para 17-19). Yokoo teach that mesenchymal stem cells derived from mammals can be differentiated into erythropoietin-producing organoids (page 3 para 44). These EPO producing organoids are taught to be beneficially used for the treatment of kidney disease or EPO deficiency (page 1 para 1, page 2 para 32). The mesenchymal stem cells may be found in the bone marrow (non-renal)(page 1 para 8) or other sites such as blood flow or umbilical cord blood (non-renal)(page 3 para 38).
Orne of ordinary skill in the art would have been motivated to use non-renal mesenchymal stem cells in the cell cluster microsphere of Mineau-Hanschke because Mineau-Hanschke are making cell cluster microspheres (including EPO producing cells as motivated by Basu ‘369) and Yokoo teach that non-renal sources of mesenchymal stem cells are a suitable cell type for the formation of EPO producing organoids (cell clusters). One of ordinary ski in the art would have had a reasonable expectation of success because both Mineau-Hanschke and Yokoo are using cells for therapeutic use.
Therefore, the combined teachings of Mineau-Hanschke, Lu et al, Basu '369 and Yokoo et al render obvious Applicant's invention as claimed.
Claims 1 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Mineau-Hanschke (WO 97/15195) in view of Lu et al (Journal of Tissue Engineering and Regenerative Medicine, 2012) and Basu et al (WO 2012/064369-from IDS filed 06/15/2022) as applied to claims 1, 7-9, 16, 25, 53, 56 and 58-62 above and further in view of Basu et al (WO 2011/156642-hereinafter referred to as ‘Basu ‘642’-from IDS filed 06/15/2022).
Regarding claims 1 and 55, the combined teachings of Mineau-Hanschke, Lu et al and Basu '369 render obvious Applicant's invention as described above, but do not specifically teach including non-renal adipose derived progenitor cells.
Basu ‘642 teach wherein cells derived from adipose tissue are a novel source of EPO (page 2 lines 28-30). Renal and non-renal sources of adipose tissue are both taught to be suitable alternatives and also include cells derived from an adipose stromal vascular fraction (SVP) which include progenitor cells (page 2 lines 29-34). These EPO producing cells are taught to be beneficially used for the treatment of kidney disease or EPO deficiency (page 14 lines 28-35).
One of ordinary skill in the art would have been motivated to use adipose derived cells that express EPO, specifically progenitor cells from the SVF of adipose tissue, in the cell cluster microsphere of Mineau-Hanschke because Mineau-Hanschke is making a cell cluster microsphere (include EPO producing cells as motivated by Basu ‘369) and Basu ‘842 teaches that non-renal sources of adipose tissue derived EPO producing cells are a suitable alternative for renal sources of EPO producing cells. One of ordinary skill in the art would have had a reasonable expectation of success because both Mineau-Hanschke and Basu ‘842 are using cells for therapeutic use.
Therefore, the combined teachings of Mineau-Hanschke, Lu et al, Basu '369 and Basu ‘842 render obvious Applicant's invention as claimed.
Claims 8 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Mineau-Hanschke (WO 97/15195) in view of Lu et al (Journal of Tissue Engineering and Regenerative Medicine, 2012) and Basu et al (WO 2012/064369-from IDS filed 06/15/2022) as applied to claims 1, 7-9, 16, 25, 53 and 56-62 above and further in view of Kazanecki et al (US 2012/0301958- hereinafter referred to as ‘Kazanecki’-from IDS filed 06/15/2022)
Regarding claims 8 and 57, the combined teachings of Mineau-Hanschke, Lu et al and Basu '369 render obvious Applicant's invention as described above, but do not specifically teach wherein the endothelial cell population is a cell line, but using cell lines as a source of cells is an obvious alternative to primary tissue sources and a skilled artisan would have been motivated with a reasonable expectation of success to use a cell line as a source of endothelial cells as a well-known alternative.
In addition, Kazanecki teach that mammalian vascular endothelial cells intended for use in a bioartificial construct with kidney cells may be obtained from cell lines or primary sources (page 2 para 20) which provides evidence that cell lines are well known alternatives to primary cells. The use of cell lines would have required that the cells were cultured separately prior to co-culture of the cells as spheroids.
Therefore, the combined teachings of Mineau-Hanschke, Lu et al, Basu '369 and Kazanecki et al render obvious Applicant's invention as claimed.
Response to Arguments
Applicant’s arguments with respect to claim(s) xxx have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lin et al., “Magnetic Reconstruction of Three-Dimensional Tissues from Multicellular Spheroids”, TISSUE ENGINEERING: Part C, 2008, Volume 14, Number 3, pp. 197-205
Hristov et al., “Endothelial Progenitor Cells Mobilization, Differentiation, and Homing”, Arteriosclerosis, Thrombosis, and Vascular Biology, 2003, Volume 23, Issue 7, Pages 1185-1189.
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 LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631