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 01/27/2025.
Claims 1-22 have been newly canceled and claims 23-30 have been newly added.
Claims 23-30 have been examined on their merits.
Claim Objections
Claims 23 and 27 are objected to because of the following informalities:
Claim 23 recites the abbreviation “MSC” in line 6. An abbreviation should be preceded in its first occurrence by the specific identity of the entity which said abbreviation is intended to represent. Thereafter, the use of the abbreviation in the claims will be understood.
In the current case the claim should state “mesenchymal stem cells (MSC)” in line 3 of the claim.
Claim 27 appears to have a typo in line 3 of the claim between “CD105low” and “CD 248-“. There should be a slash between these two markers and “;65” appears to be an artifact from a cut and paste.
Appropriate correction is required.
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.
Claims 24-30 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.
Claim 24 recites the phrase “culturing a mesenchymal stem cell colony in a culture medium with FVF2 to obtain mesenchymal stem cells lines, and contacting the expanded MSC population to a culture medium “at lines 6-8 of claim 24.
The term FVF2 appears to be a typo as there is no recitation of FVF2 in Applicant’s specification.
It appears that Applicant intends to claim “fibroblast growth factor 2 (FGF2)” as this abbreviation is disclosed in the Specification (see page 7 para 29 of the Specification).
However, it is unclear how the step for expanding the population of MSCs in vitro leads to the step for culturing a MSC colony in a culture medium with FGF to obtain MSC lines and then leads to contacting the expanded MSC population to a culture medium comprising an effective amount of SPC and TGF-beta to promote differentiation of the contacts MSC population into smooth muscle cells. Primarily it is unclear how the formation of MSC lines from the MSC colony cultured with FGF2 fits into the method of obtaining smooth muscle cells.
Since the metes and bounds of the claimed method are unclear the claim is deemed indefinite.
Appropriate correction is required.
Because claims 25-30 depend from indefinite claim 24 (as well as claim 23 which has been examined) and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph with regard to their dependence on claim 24.
Claims 25-30 have been examined in so far as their dependence on definite claim 23.
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) 23, 25-30 are rejected under 35 U.S.C. 103 as being unpatentable over Ross et al (The Journal of Clinical Investigation 2006) in view of Harris et al (The Journal of Surgical Research, 2011) and Kubota et al (The Journal of Experimental Medicine, 2011).
Regarding claims 23, 29-30, Ross et al teach steps for culturing a human mesenchymal progenitor cell in serum-free medium with TGFß1 on a fibronectin-coated plate to produce vascular smooth muscle cells (vasculogenic cells) (page 3146, Methods).
While selection of a clonal population is not explicitly described Ross suggest that a clonal population would be preferred as the results would be less likely to be compromised by contamination (page 3145, 2nd column, last paragraph). Both a clonal cell and polyclonal cells would provide greater purity than passaged cultures.
Therefore, the selection of a clonal or polyclonal population would be obvious as the artisan of ordinary skilled would have been motivated with a reasonable expectation of success by Ross' suggestion that doing so would provide results less likely to be compromised by contamination (page 3145, 2nd column, last paragraph).
Ross do not specifically mention using SPC as a factor to promote differentiation of mesenchymal progenitors to vasculogenic smooth muscle cells.
Harris teach methods for differentiating mesenchymal stem cells from adipose tissue into smooth muscle cells by culturing them in a medium containing SPC and TGFß1 on collagen gel and find that the contacted cells exhibit contractile properties similar to smooth muscle controls (abstract, pages 7-8). The SPC is taught to be at 2 µM and the TGFß1 is at 2 ng/ml (page 3, 2ⁿᵈ paragraph). This is taught to have important implications for vascular tissue engineering because contractility adds functional properties to a vascular graft that are similar to native arteries. It provides added strength to the graft, thereby increasing the ability of the graft to withstand physiological stresses (page 7).
Therefore, one of ordinary skill in the art would have been motivated to include about 2 µM of SPC in the culture medium of Ross to enhance the differentiation of the adult stem cells towards smooth muscle cells because Harris teach that both SPC and TGFß1 provide cells that exhibit contractile properties similar to smooth muscle controls and Harris teach that this is beneficial for providing smooth muscle cells for vascular tissue engineering. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (MPEP 2144.06). One of ordinary skill in the art would have had a reasonable expectation of success because both Ross and Harris are differentiating adult stem cells with TGFß1 plus additional factors for the production of smooth muscle cells for vascular tissue engineering.
The combined teachings of Ross et al and Harris et al render obvious Applicant's invention as described above, but do not describe wherein the mesenchymal progenitors are derived from mesenchymoangioblasts.
Kubota et al teach that human mesenchymoangioblasts have been identified as a common endothelial and mesenchymal precursor within a mesodermal subset and has a potential to differentiate into several different cell types including mesenchymal stem cells and vasculogenic cell types (page 957 column 1).
Therefore, one of ordinary skill in the art would have been motivated with a reasonable expectation of success to select mesenchymoangioblasts or mesenchymal progenitor cells derived from mesenchymoangioblasts as a starting cell population for the method of Ross et al because Kubota et al indicate that these cells are similar to those cells that produce mesenchymal stem cells and vasculogenic cells such as smooth muscle cells (page 949- 950). One of ordinary skill in the art would have been motivated with a reasonable expectation of success to obtain mesenchymal stem cells derived from the mesenchymoangioblasts and then use them to differentiate and produce smooth muscle cells in the method of Ross because Harris teach and suggest that mesenchymal stem cells can differentiate into smooth muscle cells by culturing them in a medium containing SPC and TGFß1 on collagen gel and find that the contacted cells exhibit contractile properties similar to smooth muscle controls (abstract, pages 7-8).
Ross do not recite steps for obtaining MSCs from the MAB-derived colony of progenitors and expanding these MSCs prior to differentiating them into smooth muscle cells, these limitations would have been obvious based on the teachings of Harris and Kubota.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to obtain mesenchymal stem cells derived from the mesenchymoangioblasts, expanding them to increase their numbers and then use them to differentiate and produce smooth muscle cells in the method of the Ross because Harris teach and suggest that mesenchymal stem cells can differentiate into smooth muscle cells by culturing them in a medium containing SPC and TGFß1 on collagen gel and find that the contacted cells exhibit contractile properties similar to smooth muscle controls (abstract, pages 7-8). Kubota et al indicate that human mesenchymoangioblasts are similar to those cells that produce mesenchymal stem cells and vasculogenic cells such as smooth muscle cells (page 949- 950). Expansion of cells is an obvious modification to include in order to optimize the cells produce by the method.
Regarding claim 27, While Kubota is silent with regard to the expression of the markers claimed by Applicant, it would appear that mesenchymoangioblasts or mesenchymal progenitor cells derived from mesenchymoangioblasts would inherently express these markers in at least some of their cells baring evidence to the contrary.
Regarding claims 25-26, Ross teach wherein the isolated vasculogenic cells express at least one molecular marker of smooth muscle cells, such as α-SMA, calponin, SM22, myocardin, and smooth muscle myosin heavy chain (SM-MHC) (page 3141, Figure 2, columns 1-2).
Regarding claim 28, Ross teach wherein the mesenchymal progenitors are human (page 3145, 2ⁿᵈ column, last paragraph).
Therefore, the combined teachings of Ross et al, Harris et al and Kubota et al render obvious Applicant's invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 23, 25-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,091,738 in view of Harris et al (The Journal of Surgical Research, 2011) and Kubota et al (The Journal of Experimental Medicine, 2011).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent are also drawn to a method of generating an isolated population of primate vasculogenic cells comprising contacting a colony of primate mesenchymal progenitors to a culture medium comprising SPC and TGF-beta to promote differentiation and cultured to smooth muscle cells expressing at least one marker of smooth muscle cells.
While the patented claims do not recite steps for obtaining MSCs from the MAB-derived colony of progenitors and expanding these MSCs prior to differentiating them into smooth muscle cells, these limitations would have been obvious based on the teachings of Harris and Kubota.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to obtain mesenchymal stem cells derived from the mesenchymoangioblasts, expanding them to increase their numbers and then use them to differentiate and produce smooth muscle cells in the method of the patent because Harris teach and suggest that mesenchymal stem cells can differentiate into smooth muscle cells by culturing them in a medium containing SPC and TGFß1 on collagen gel and find that the contacted cells exhibit contractile properties similar to smooth muscle controls (abstract, pages 7-8). Kubota et al indicate that human mesenchymoangioblasts are similar to those cells that produce mesenchymal stem cells and vasculogenic cells such as smooth muscle cells (page 949- 950). Expansion of cells is an obvious modification to include in order to optimize the cells produce by the method.
Therefore, the combined teachings of the patent claims, Harris et al and Kubota et al render obvious the current claims.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Xiong, Anqi, "Characterization of mesenchymal stem/progenitor cells and their progeny from non-fetal tissue sources", http://www.uu.se/digitalAssets/167/167898_3angi-xiong-report.pdf,pp 1-25.
Vodyanyk et al., “Generation Of Clonal Mesenchymal Progenitors And Mesenchymal Stem Cell Lines Under Serum-Free Conditions”, US 2011/0236971.
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
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