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 Action
This Office Action is in response to the Applicant’s reply received 7/21/26. Claims 1, 25-30, and 33-46 and considered on the merits.
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, 25-30, 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 1, 25, and 26.
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.
Oharuda I teach the stem cells can be embedded in the device and differentiated after administration into the subject [0065]. This appears to mean the stem cells administered with the device are not induced to differentiate until after implantation. Furthermore, Oharuda I teach that the stem cells “can be induced to differentiate”, leaving induction or non-induction of the cells as alternative embodiments (0065, 1st sentence). Also since Oharuda I teach both stem cells and induced pluripotent stem cells (iPS), then it would be obvious for one of ordinary skill to select either induced or non-induced stem cells since these are alternative embodiments.
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, 25-30, 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) 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 1, 25, and 26.
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.
In Reference Example 7 (col 31, line 50), Oharuda II cultures the MSCs, but does not expressly include any compound or step that would induce the MSCs. These non-induced MSCs are used in Example 1 (col 35, line 40) and Comparative Examples 1 and 2 (col 35, line 55 to col 35, line 15) to form and implant the device to induce blood vessel formation. When considering the construction and implantation of the device from Reference Example 7 to the Comparative Examples 1 and 2, one of ordinary skill would recognize that the MSCs used are non-induced since no induction step is recited.
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 argues that Oharuda I and II do not teach excluding stem cells which are induced to differentiate. The Examiner does not disagree that both Oharuda I and II include options for using differentiated cells, stem cells, or iPS cells. However as cited in the rejections above, both teach using non-induced stem cells as an alternative embodiment. MPEP 2173.05(i) state “If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims”. This is the rational used for both rejections using Oharuda I and II. They teach using both induced and non-induced cells, therefore it would be obvious for one of ordinary skill to use the non-induced cells in their device.
Conclusion
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.
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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