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 7/13/26. Claims 1-3,27-28,30-33 and 36-57 are pending and considered on the merits.
Claim Interpretation
The claims have been amended to include the following wherein clause:
wherein the angiogenesis device has a rate of volume shrinkage of 20% to 90% as a rate of volume change before and after immersion in water at a temperature of 37°C, and the rate of volume shrinkage is calculated by the following formula:
Rate of volume change(%)= (volume after placement or immersion in water for one month)/(volume before placement or immersion in water) x 100.
MPEP 2111.04 states “Claim scope is not limited by claim language … that does not limit a claim to a particular structure.” In this case the shrinkage of the device is directly related to the structure of the device. Since this wherein clause does not alter the structure of the device, prior art reading on the claimed structure will also read on these results/properties.
New Rejections Necessitated by Amendment
These new rejections are necessitated by that latest amendment. They are presented first because they influence claim interpretation.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 27-28, 30-33 and 36-57 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The formula:
Rate of volume change(%)= (volume after placement or immersion in water for one month)/(volume before placement or immersion in water) x 100
is not fully supported in the Specification. The issue is “volume after placement”. The Specification supports “volume after immersion” but not the broader term “placement”. This is an issue because placement can have a range of meanings including floating on top of the water with limited surface area exposed to water to complete submersion in water. It is not clear if the formula is robust enough to account for less than all of the devices surface area exposed to water. Since water exposure is critical to shrinking, it is unclear if less exposure will alter this result and if the formula can account for this variable.
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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 1-3 require “a rate of change of volume change before and after immersion in water”. However the formula for “Rate of volume change (%)” includes a broader condition of “volume after placement or immersion in water” which contradicts the prior “after immersion in water” condition. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 of Rejections concerning Oharuda I and Oharuda II in view of Tsuji et al.
Applicant's arguments have been fully considered but they are not persuasive. The Applicant argues that since Oharuda I and II teach their devices “retain their form without any collapse” and are “strong enough not to be decomposed in the body” this precludes the claimed shrinking properties. This argument is not persuasive because shrinking does not seem directly related to collapsing or decomposition. The Applicant does provide a clear nexus or evidence that not collapsing or decomposing is equivalent to not shrinking.
Concerning the inherent properties of the device of Oharuda I and II, the only difference between the claimed invention and those of either prior art is the origin of the stem cells. Oharuda I and II teach their devices comprises mesenchymal stem cells (MSCs) and not adipose derived stem cells. However the polyvinyl alcohol resins disclosed by Oharuda I and II directly overlap with those claimed. MPEP 2112.01 II state:
A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Since the chemical composition of the polyvinyl alcohol resins of both Oharuda I and II is the same, then it must have the same properties. There has been no evidence that the source of stem cells will alter the properties of this device. Furthermore, since adipose derived stem cells are considered mesenchymal stem cells (see Tsuji, Abstract, 1st line) then it appears Oharuda I and II are nearly identical in structure and therefore will be identical in properties.
MPEP 2141.02 V is state disclosed inherent properties are part of “as a whole” inquiry. In this case, the teachings of both Oharuda I and II teach the claimed limitations of the structure of the resin of the device and only differ in the source of the mesenchymal stem cells are from the adipose tissue. However it was not presented that the source of the stem cells would alter the structure which would change the shrinking properties of the device. In particular since adipose-derived stem cells are considered a species of the genus mesenchymal stem cells.
In summary, since Oharuda I and II teach a device with the same polyvinyl alcohol resin as claimed, then the properties including the shrinking of this resin are considered inherently met. The only point of obviousness hinges on adipose-derived stem cells as opposed to the mesenchymal stem cells taught in Oharuda I and II. However since adipose-derived stem cells are also MSCs, then it appears the devices of Oharuda I and II are sufficiently identical that their properties are identical as well.
Claim(s) 30 remain 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 remain 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.
Response To Applicant’s Arguments of Rejections of claim 30
Applicant is reminded that M.P.E.P. § 2123 states:
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." And furthermore “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments”.
Applicant agues the PVA implants of Diegelmann et al. cause inflammation of the wound. However Diegelmann et al. is not used for its PVA implants, only to teach that it would be obvious to remove the subcutaneous PVA implants of Oharuda I or II with a needle without causing one of bleeding, inflammation, and rupture of a blood vessel. In particular inflammation with a sterile needle.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
Prosecution Insights