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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/25/26 has been entered.
Detailed Action
This Office Action is in response to the Applicant’s reply received 3/25/26. Claims 1, 25-30, and 33-46 are pending. No Claims are withdrawn. Claims 1, 25-30, and 33-46 are considered on the merits.
Response to Applicant’s Arguments and Amendments
In the response submitted by the Applicant the following 35 U.S.C § 103 (a) rejections are withdrawn:
Claim(s) 25, 26-31, 33, 36-39, and 42-46 were rejected under 35 U.S.C. 103 as being unpatentable over Oharuda I (WO 2018/155622) in light of support by Adair et al. (Angiogenesis, Chapter 1, 2010).
Claim(s) 25, 26-28, 31, 33-36, and 38-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda II (WO 2018/155621) in light of support by Adair et al. (Angiogenesis, Chapter 1, 2010).
The Applicant’s amendments limiting the method to using a adipose derived stem cells necessitated the above withdrawals. All arguments drawn to these rejections are now considered moot.
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.
Claim(s) 1 and 32 and now 25, 26-30, 33, 36-39, and 42-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda I (WO 2018/155622) in light of support by Adair et al. (Angiogenesis, Chapter 1, 2010), and further in view of Orbey et al. (Stem Cells International 20212). WO2018/155622 is in Japanese. US 2020/0231960 is an English-language equivalent. All citations are to this US document for convenience. This rejection has been modified to accommodate amendments to claims 25, 26-31, 33, 36-39, and 42-46.
Oharuda I teach a cell or tissue embedding in a aqueous gel that serves as an immunoisolation layer for subcutaneous implantation and effective building of a vascular network (See Fig 6 and [0027]). The phrase “effective building of a vascular network” in Fig. 6 reads as angiogenesis since this is inside the common-use definition of “the growth of blood vessels from the existing vasculature” (Adair, Overview of Angiogenesis, 1st line). They teach the gelled implant is easily removed and/or replaced (See Fig 6 and [0138-0139]). The immunoisolation of the gelled implant will reduce the chance of inflammation since antibodies and immune cells will not have access to the cells inside the implant (See Fig 5). This aqueous gel implant comprises polyvinyl alcohol (PVA) ([0017] point 1) resin with the following properties:
syndiotacticity of 32-40% ([0017] point (1)),
a stress of 0.3 to 30 kPa at 20°C (([0017] point (3) and [187])
a saponification degree of 90-99.99 mol% ([0017] point (4) and [150]),
a polymerization degree of 100-1000 ([0017] point (4)),
The PVA comprises vinyl pivalate units which has an active carbonyl group (([0017] point (5) and [150]),
a cell culture component ([0017] point (6)) comprising an acetate or phosphate buffer ([0017] point (9)); and
a cell culture component ([0017] point (6)) selected from a list of cells, including mesenchymal stem cells (MSCs) as the angiogenic component (([0017] point (7));
Oharuda I teach the MSCs are embedded in the gel by mixing the cell culture component with a solution containing PVA ([0017] point 13). This mixture is then gelled. This mixing followed by gelling would produce a composition where the MSCs are dispersed within the polymer. This gelled polymer then forms a scaffold to hold the cells to prevent migration. Figs 1-3 show the device can be implanted for 1-28 days which is interpreted as the implant can be left in the site for two months or less.
What Oharuda I do not teach is the MSCs are adipose stem cells. However this would be obvious in view of Orbay et al. who teach MSCs are obtained from many sources, but are very abundant and easily harvested from adipose tissue (Orbay, pg. 2, Section 2). Therefore one of ordinary skill in the art would consider it obvious to use MSCs from adipose tissue since they are easy to obtain in larger quantities than other sources.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1 and 32 and now 25, 26-30, 33-36, and 38-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda II (WO 2018/155621) in light of support by Adair et al. (Angiogenesis, Chapter 1, 2010) as applied to claims 25, 26-28, 31, 33-36, and 38-46 above, and further in view of and further in view of Orbey et al. (Stem Cells International 20212). WO 2018/155621 is in Japanese. US 11684693 is an English-language equivalent. All citations are to this US document for convenience. This rejection has been modified to address the amendments to claims 25, 26-28, 31, 33-36, and 38-46.
Oharuda II teach a cell or tissue embedding in a aqueous gel that serves as an immunoisolation layer for subcutaneous implantation and angiogenesis (See Fig 7 and col 6, lines 15-20). They teach the gelled implant is easily removed and/or replaced (See Fig 7, col 20, lines 50-60). The immunoisolation of the gelled implant will reduce the chance of inflammation since antibodies and immune cells will not have access to the cells inside the implant (See Fig 7). The aqueous gel comprises polyvinyl alcohol (PVA) resin with the following properties:
a activated carbonyl group (col 3, point (1));
a stress of 0.3 to 30 kPa at 20°C ( col 3, point (3) and Example 22)
a diacetone acrylamide-denatured polyvinyl alcohol with 0.5-15 mol % diacetone acrylamide unit (col 3, points (4) and (5)),
a hydrazide or semicarbazide crosslinking agent (col 3, point (4)),
a polymerization degree after crosslinking is 3000-8000 (col 11 lines 15-25),
a cell culture component that comprises mesenchymal stem cells (col 3, point (9)) and acetate or phosphate buffer (col 3, point (11));
a saponification degree of 80-99.9 mol % (col 10 lines 5-10).
Oharuda II teach the cells are embedded in the gel by mixing the cell culture component with a solution containing PVA (col 3, point 25). This mixture is then gelled. This mixing followed by gelling would produce a composition where the cell is dispersed within the polymer. This gelled polymer then forms a scaffold to hold the cell to prevent migration. Figs 1-3 show the device can be implanted for 1-28 days which is interpreted as the implant can be left in the site for two months or less.
What Oharuda II do not teach is the MSCs are adipose stem cells. However this would be obvious in view of Orbay et al. who teach MSCs are obtained from many sources, but are very abundant and easily harvested from adipose tissue (Orbay, pg. 2, Section 2). Therefore one of ordinary skill in the art would consider it obvious to use MSCs from adipose tissue since they are easy to obtain in larger quantities than other sources.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response To Applicant’s Arguments
Applicant's arguments have been fully considered but they are not persuasive. The Applicant combined both arguments for Oharuda I and Oharuda II. For convenience, this response will be for both rejections as well. Applicant argues there is no motivation to use adipose-derived stem cells (ASCs) for they mesenchymal stem cells (MSCs) and this substitution lacks a reasonable expectation for success. Initially both Oharuda I and II teach using MSCs in their invention. Orbay et al. simply teach a source of MSCs is adipose tissue, making the MSCs adipose derived. Orbay et al. teach that all MSCs are suitable for clinical use and that ASCs have multilineage differentiation capacity of other MSCs (Orbay, pg. 4, 2nd column, Section 12). One of ordinary skill would recognize ASCs have similar properties to other MSCs and are known for clinical uses and therefore suitable for use in the composition of Oharuda I and Oharuda II with reasonable expectation of success.
The Applicant argues that the claimed device efficiently induces angiogenesis and can also facilitate retrieval. However both Oharuda I and II expressly teach their devices induce angiogenesis by “effective building of vascular network” and is “easy to remove and replace” (Oharuda I, Fig. 6 and Oharuda II, Fig. 7). Therefore this argument is not persuasive without additional evidence on how the current claim device and method are superior. Also both teach that their devices have immunoisolation properties so will also reduce inflammation while implanted and retried and reimplanted. Therefore these arguments without evidence are not persuasive in light of the expressed teachings of Oharuda I and II. Furthermore the structure of the device of taught by both Oharuda I and II are nearly identical to those claimed except for the source of the MSCs. MPEP 2112.01 II states “Products of identical chemical composition can not have mutually exclusive properties”. Therefore since Oharuda I and II are very similar to the current claims, then they should have similar properties when implanted.
Also while the applicant argues their Examples and Comparative Examples provide evidence of unexpected results, they do not cite any data in those examples or any refer to any specific results to support unexpected results. MPEP 716.02(b) is state it is the Applicant’s burden to I) Establish Results are unexpected and significant and II) Explain Proffered Data. In particular, if adipose as the source of MSCs is superior to other sources, this can be shown as an unexpected result by a comparative test. The same could be considered if the claimed invention was easier to remove and re-implant that that disclosed by Oharuda I or II.
In response to this office action the applicant should specifically point out the support for any amendments made to the disclosure, including the claims (MPEP 714.02 and 2163.06).
CONTACT INFORMATION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THANE E UNDERDAHL whose telephone number is (303) 297-4299. The examiner can normally be reached Monday through Thursday, M-F 8-5 MST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
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