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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/25/26 has been entered.
Response to Applicant’s Arguments and Amendments
In the response submitted by the Applicant the following 35 U.S.C § 102 rejections are withdrawn:
Claim(s) 27, 28, 31-34, 36, 39-42, and 45-53 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oharuda I (WO 2018/155622).
Claim(s) 27, 28, 31-34, 36-39, and 41-53 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oharuda II (WO 2018/155621).
The following 35 USC 103 rejections are withdrawn.
Claim(s) 27, 28, 30-34, 36, 39-42, and 45-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda I (WO 2018/155622) in view of Diegelmann (J. Surg Res, 1986) and in light of support by New England Small Tube Corp. (Hypodermic Gauge Sizes, 2017). WO2018/155622 is in Japanese. US 2020/0231960 is an English-language equivalent. All citations are to this US document for convenience;
Claim(s) 27, 28, 30-34, 36-39, and 41-53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda II (WO 2018/155621) in view of Diegelmann et al. in light of support by New England Small Tube Corp. (Hypodermic Gauge Sizes, 2017)
The Applicant’s amendments the cell- or tissue-containing device comprises both adipose-derived stem cells and a biological composition with differentiated 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) 1-3, 27, 28, 31-33, 36, 39-42, and 45-57 remain rejected under 35 U.S.C. 103 as being unpatentable over Oharuda I (WO 2018/155622) in view of Tsuji et al. (WJSC, 2014). 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 meet the new and amended claims.
Oharuda I teach a cell or tissue embedded in a aqueous gel that serves as an immunoisolation layer for subcutaneous implantation and angiogenesis (See Fig 6 and [0027]) to treat diseases in a human (0017). They teach the gelled implant is easily removed and 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). The gel comprises polyvinyl alcohol (PVA) 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 (([0017] point (5) and [150]) which have an active carbonyl group,
a biological component ([0017] point (6)) comprising an acetate or phosphate buffer ([0017] point (9)); and
an angiogenic component ([0017] point (6)) that comprises one or more cells including mesenchymal stem cells (MSCs), hepatocytes, and pancreatic islet cells (([0017] point (7));
Oharuda I teach the cells 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 cell is dispersed withing the polymer. This gelled polymer then forms a scaffold to hold the cell to prevent migration.
Oharuda I teach their device can be implanted from 0-28 days and remain functional (Fig 1 and Fig 2). Oharuda I teach the device can be removed and replaced (00138-00139). The replacement device would read as implanting a cell-containing device into a site where the angiogenesis devices has been implanted and subsequently retrieved. The claims do not require that cell- or tissue-containing device differs from the angiogenesis device described in the claims. Therefore removing the device of Oharuda I and replacing it with another of the same design continues to read on these claims.
While Oharuda I teach their device comprises one or more cells selected from mesenchymal stem cells (MSCs), hepatocytes, and pancreatic islet cells, they do not expressly teach combining these cells. However this is obvious according to teachings elsewhere in Oharuda I who teach a combination of pancreatic islet cells, hepatocytes and stem cells [0068] is suitable for this device.
While Oharuda I teach their device comprises MSCs, they do not specifically adipose-derived stem cells (ASCs). This would be obvious in view Tsuji et al. who teach ASCs are MSCs obtained from adipose tissue (Tsuji, Abstract). Therefore it would be obvious to use ASCs in the invention of Oharuda I since Tsuji et al. is clear ASCs are MSCs isolated from adipose tissue. One of ordinary skill in the art would recognize this a simple substitution of MSCs sourced from adipose tissue (MPEP 2141 III (B) and 2144.06 II).
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) 1-3, 27, 28, 31-33, 36-39, and 41-57 were rejected under 35 U.S.C. 103 as being unpatentable over Oharuda II (WO 2018/155621) in view of Tsuji et al. (WJSC, 2014). 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 meet the new and amended claims.
Oharuda II teach a cell or tissue embedded 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). 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 6). The gel comprises polyvinyl alcohol (PVA) resin with the following properties:
a activated carbonyl group (col 3, point (1));
a stress of 0.5 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 (MSCs) and pancreatic islet cells (col 3, point (9)) with 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. Oharuda II teach that device can be implanted from 1-28 days (see Figs 2-3) or even as long as 1-185 days (see Fig 1).
Oharuda II teach this device can be removed and replaced (col 20, lines 50-60 and Fig 7)). The replacement device would read as implanting a cell-containing device into a site where the angiogenesis devices has been implanted and subsequently retrieved. The claims do not require that cell- or tissue-containing device differs from the angiogenesis device described in the claims. Therefore removing the device of Oharuda II and replacing it with another of the same design continues to read on these claims.
While Oharuda II teach their device comprises one or more cells selected from mesenchymal stem cells (MSCs), hepatocytes, and pancreatic islet cells, they do not expressly teach combining these cells. However this is obvious according to teachings elsewhere in Oharuda II who teach a combination of pancreatic islet cells, hepatocytes and stem cells (col 13, lines 25-30) is suitable for this device.
While Oharuda II teach their device comprises mesenchymal stem cells (MSCs) and not specifically adipose-derived stem cells (ASCs) this would be obvious in view Tsuji et al. who teach ASCs are MSCs obtained from adipose tissue (Tsuji, Abstract). Therefore it would be obvious to use ASCs in the invention of Oharuda II since Tsuji et al. is clear ASCs are MSCs isolated from adipose tissue. One of ordinary skill in the art would recognize this a simple substitution of MSCs sourced from adipose tissue (MPEP 2141 III (B) and 2144.06 II).
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. Applicant combines their arguments to address both Oharuda I and Oharuda II, which will be referred to as The Oharuda references.
The Applicant argues that Oharuda references do not teach an angiogenesis device with adipose-derived stem cells (ASCs) to prevent or improve any diseases or symptoms. The Applicant is correct that the Oharuda references teach using MSCs and not ASCs. However Tsuji et al. is clear that ASCs are MSCs obtained from adipose tissue (Tsuji, Abstract), so it would be obvious to substitute ASCs for the MSCs in either Oharuda reference since these are suitable mesenchymal stem cells. Also the Oharuda references teach their implants comprising MSCs and pancreatic islet cells are for treating endocrine and metabolic diseases (Oharuda I and II, see Technical Field in either document).
The Applicant argues that the claimed device enhances angiogenesis once implanted which greatly improves its retrieval because bleeding, inflammation, and exudate release is reduced at the implantation site. The Applicant points to Example 1 and paragraphs [0213] and [0224]. However the implant used in Example 1 does not appear to be commensurate in scope with the claims. This implant requires a PET mesh to support the ADCs [0212] which is not in the claims. The implant also comprises a combination an aqueous gel of D-PVA 1 and APA 1. These polymers do not have all of the properties listed in claims (A1-A3) and there is no evidence that the unexpected results would occur for all of the configurations of the PVA resin. For example, D-PVA 1 does have a degree of saponification of 98.4 mol% [0197], but it is not clear what is its triad syndiotacticity or if it has an active carbonyl group. APA 1 does not appear to have any of the properties listed in claims 1-3, 27 or 28. MPEP 716.02(d) state “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.”. In this case, cited Example 1 does not provide sufficient evidence to show the unexpected results will occur for implants made with all the PVAs with the properties listed as A1-A3 in the claims.
The Examiner acknowledges that polymer properties and their results on implantation is a very nuanced topic. The Applicant is encouraged to contact the Examiner for an interview to see if any claim amendments are possible to place this case in condition for allowance.
New Rejections Necessitated by Amendment
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda I (WO 2018/155622 with US 2020/0231960 as a translation cited for convenience) and Tsuji et al. (WJSC, 2014) as applied to claims 1-3, 27, 28, 31-33, 36, 39-42, and 45-57 above, and further in view of Diegelmann et al. in light of support by New England Small Tube Corp. (Hypodermic Gauge Sizes, 2017).
Oharuda I and Tsuji et al. render obvious the method of using the angiogenesis device of claim 27. Oharuda I teach that these device can be removed and replaced (00138-00139). The replacement device would read as implanting a cell-containing device into a site where the angiogenesis devices has been implanted and subsequently retrieved. The claims do not require that cell- or tissue-containing device differs from the angiogenesis device described in the claims. Therefore removing the device of Oharuda I and replacing it with another of the same design continues to anticipate these claims.
What Oharuda I does not expressly teach is that the angiogenesis is retrieved without bleeding, inflammation, and/or rupture of a blood vessel. However this would be obvious in view of Diegelmann et al. who teach placing PVA implants with a 12 gauge needle. A 12 gauge needle has an internal diameter of about 0.083-0.099 inches which converts to 2.1-2.5 mm as supported by New England Small Tube Corp., which is larger than the sizes of the devices disclosed by Oharuda I which are as small as 0.1-0.5 mm (0072). Therefore it would be obvious to implant the devices of Oharuda I with a 12 gauge syringe since this will place the device subcutaneously, with no bleeding, inflammation and/or rupture of a blood vessel. One of ordinary skill would recognize this as simply applying a known method to implant PVA devices subcutaneously (MPEP 2141 III (B) and (D)).
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) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oharuda II (WO 2018/155621 with US 11684693 as a translation cited for convenience) and Tsuji et al. (WJSC, 2014) as applied to claims 1-3, 27, 28, 31-33, 36-39, and 41-57 above, and further in view of Diegelmann et al. in light of support by New England Small Tube Corp. (Hypodermic Gauge Sizes, 2017).
Oharuda II and Tsuji et al. render obvious the method of using the angiogenesis device of claim 27. Oharuda II teach that these device can be removed and replaced (col 20, lines 50-60 and Fig 7)). The replacement device would read as implanting a cell-containing device into a site where the angiogenesis devices has been implanted and subsequently retrieved. The claims do not require that cell- or tissue-containing device differs from the angiogenesis device described in the claims. Therefore removing the device of Oharuda II and replacing it with another of the same design continues to read on these claims.
What Oharuda II does not expressly teach is that the angiogenesis is retrieved without bleeding, inflammation, and/or rupture of a blood vessel. However this would be obvious in view of Diegelmann et al. who teach placing PVA implants with a 12 gauge needle. A 12 gauge needle has an internal diameter of about 0.083-0.099 inches which converts to 2.1-2.5 mm as supported by New England Small Tube Corp., which is larger than the sizes of the devices disclosed by Oharuda II which are as small as 0.1-0.5 mm (col 13, lines 60-65). Therefore it would be obvious to implant the devices of Oharuda II with a 12 gauge syringe since this will place the device subcutaneously, with no bleeding, inflammation and/or rupture of a blood vessel. One of ordinary skill would recognize this as simply applying a known method to implant PVA devices subcutaneously (MPEP 2141 III (B) and (D)).
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.
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