*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 .
Applicant’s response dated July 30, 2026 is acknowledged.
Priority
This application is a 371 of PCT/JP2020/047944 filed on 12/22/2020.
Claim Status
Claims 1-19 are pending. Claim 9 is withdrawn. Claims 1-8 and 10-19 are examined.
Election/Restriction
Applicant’s election with traverse of the species of chemically crosslinked alginic acid obtained by the combination of EX2-(II)-A-2 and EX3-(I)-A2:
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, is acknowledged.
Claims 1-8 and 10-19 read on the elected species.
The traversal is on the ground that the present invention is directed to alginic acid derivatives that form chemical crosslinks via a Huisgen-type reaction or via divalent metal ions. Desai fails to disclose these types of chemical crosslink formation.
Applicant’s arguments were fully considered, however they were found unpersuasive because the broadest claim does not limit how the alginic acid is chemically crosslinked. Desai teaches chemically crosslinked alginic acid, which is sufficient to break unity of invention and show that chemically crosslinked alginic acid is not a contribution over the prior art. The restriction requirement in the current application is deemed proper because species lack unity under PCT Rule 13.1 as shown in the restriction requirement of June 4, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being withdrawn to a non-elected invention, and non-elected species of the invention, there being no allowable generic or linking claims. Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (See § 1.181.).
Response to the restriction requirement of June 4, 2026 was timely filed.
Claims 1-8 and 10-19 are examined on the merits.
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.
Claims 1-8, 16, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Desai (WO 94/15589 Published July 21, 1994 – of record in PTO-892 dated June 4, 2026) and Furusako (CA 3 103 227 Published December 19, 2019 – of record in IDS January 27, 2025).
The claims encompass a transplantation device comprising insulin-secreting cells or pancreatic islets enclosed in a hydrogel, wherein the hydrogel comprises an alginic acid derivative that has been gelled by chemical crosslinking of
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, and wherein the thickness of the hydrogel is from 100 microns to less than 500 microns.
The teachings of Desai are related to a macrocapsule for encapsulating microcapsules containing biologically active material such as living cells or free living cells (Abstract). The macrocapsule provides a system of rapid but sustained release of the material made by and secreted by the encapsulated cell(s), which in turn provides for more regulated control of physiological processes (e.g., blood glucose levels in the case of encapsulated islets) (page 10 lines 15-20). The macroencapsulated living cells are useful for transplantation (paragraph bridging pages 12-13). The term “microcapsules" refers to particles wherein the largest dimensions thereof fall in the range of about 5 microns to 4000 microns, while the term “macrocapsules” refers to particles wherein the largest dimensions thereof fall in the range of about 500 microns up to about 50 cm (paragraph bridging pages 14-15). The layer of gelled material in macrocapsules has a thickness of at least about 1 micron, with a thickness of at least about 20-40 microns being preferred, and a thickness of at least about 50 microns or greater being especially preferred. In addition, the layer of gelled material is exceptionally stable to long-term exposure to physiological conditions since the gelled material is ionically and/or covalently crosslinked to itself, and does not depend on an interaction with the incorporated material for strength and/or stability. (paragraph bridging pages 15-16). In a preferred embodiment, when microcapsules are incorporated into macrocapsules, the microcapsules and the macrocapsules are maintained in the gelled state (i.e., ionically and/or covalently crosslinked) (page 16 lines 18-22). Macrocapsules can be produced in a variety of shapes including a flat sheet among others (paragraph bridging pages 16-17).
The materials used to provide such entrapment could be alginate, or a modification of such alginate to improve its biocompatibility and stability, e.g., a polymerizable alginate allowing covalent crosslinkage, or crosslinkable or polymerizable water soluble polyalkylene glycol, or combinations of these materials. The process to cause gel entrapment of such materials can be accomplished either by ionic or covalent crosslinkage (page 17 lines 6-14).
Desai does not teach alginate obtained by reacting EX2-(II)-A-2 and EX3-(I)-A2.
The teachings of Furusako are related to alginic acid derivatives represented by formula (I) and formula (II), and crosslinked alginic acid obtained by carrying out a Huisgen reaction using an alginic acid derivative of formula (I) and an alginic acid derivative of formula (II) (Abstract). The alginic acid derivatives are suitable as medical materials including cell transplant substrates (paragraph 0257), and in the form of a gel (paragraph 0258).
Compound of formula I has the structure of formula
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(paragraph 0044), in which L1 is
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(paragraph 0049).
Compound of formula II has the structure of formula
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(paragraph 0064), in which L2 is selected from
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(paragraph 0065).
Example 3a teaches a specific compound formula II having the structure:
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(paragraph 0293).
Example 8 teaches a specific compound of formula I having the structure:
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(paragraph 0375).
The teachings of Desai and Furusako are related to chemically crosslinked alginates that are useful as cell transplant substrates, and it would have been obvious to have combined them because they are in the same field of endeavor.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed a transplantation device comprising pancreatic islets enclosed in a hydrogel, wherein the hydrogel comprises an alginic acid derivative that has been gelled by chemical crosslinking and wherein the thickness of the hydrogel is at least about 50 microns, with a reasonable expectation of success because Desai teaches a macrocapsule encapsulating cells, wherein the macrocapsule is formed from covalently crosslinked alginate derivatives, the gelled material in the macrocapsule has a thickenss of at least about 50 microns, and wherein the cells are pancreatic islets.
It would have been obvious to have formed Desai’s macrocapsule using Furusako’s crosslinked alginate formed by reacting alginate derivative of formula I and alginate derivative of formula II, with a reasonable expectation of success because Furusako teaches that crosslinked alginates formed by reacting alginate derivatives of formula I with alginate derivatives of formula II via Huisgen reaction are suitable for use as cell transplant substrates. It would have been obvious to have selected
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as the alginate derivative of formula I and
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as the alginate of formula II, with a reasonable expectation of success in making a crosslinked alginate because Furusako teaches said compounds as suitable. The selection of a known material based on its suitability for its intended purpose supports obviousness, and combining prior art elements according to known methods of obtain predictable results supports obviousness.
The claimed thickness range is obvious because overlaps with at least 50 microns.
The elected species of crosslinked alginate in claims 1-8 is obvious because Furusako teaches forming the crosslinked alginate using the same alginate derivatives as elected.
Regarding claim 16, it would have been obvious to have shaped the macrocapsule into a flat sheet, with a reasonable expectation of success because Desai teaches forming the macrocapsule into a flat sheet.
Regarding claim 17, it would have been obvious to have formed the flat sheet in the shape of a square where each side of the square ranges from 500 microns to 50 cm, with a reasonable expectation of success because Desai teaches that the flat sheet includes a square (paragraph bridging pages 16 and 17), and further teaches that macrocapsules have the largest dimensions fall in the range of about 500 microns up to about 50 cm (paragraph bridging pages 14-15). The claimed first length and second length are obvious because each of the ranges overlaps with a range from 500 microns to 50 cm.
Regarding claim 19, it would have been obvious to have formed the flat sheet in the shape of a square where each side of the square ranges from 500 microns to 50 cm, with a reasonable expectation of success because Desai teaches that the flat sheet includes a square (paragraph bridging pages 16 and 17), and further teaches that macrocapsules have the largest dimensions fall in the range of about 500 microns up to about 50 cm (paragraph bridging pages 14-15). A square having each length from 500 microns to 50 cm would have a surface area from about 0.005 cm2 to about 5000 cm2. The claimed range of surface areas is obvious because it overlaps with Desai’s range.
Claims 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Desai and Furusako as applied to claims 1-8, 16, 17, and 19 above, and further in view of Dufrane (US 2008/0050417 Published February 28, 2008).
The claims further define the pancreatic islets.
The teachings of Desai and Furusako are relied upon as summarized above, however they do not teach the limitations of claims 10-12.
The teachings of Dufrane are related to cellular devices comprising a collagen matrix, cell layer, and gelled alginate layer (Abstract). Figures describe alginate-encapsulated pig islets (paragraphs 0010-0016). In some embodiments, the pancreatic islet cells comprise cells from a neonatal pig or an adult pig (paragraph 0118).
The teachings of Dufrane and Desai modified with Furusako are related to alginate-encapsulated pancreatic islets intended for transplantation, and it would have been obvious to have combined their teachings because they are in same field of endeavor. It would have been obvious to have formed Desai’s system by encapsulating islets of an adult pig or islets of a neonatal pig the alginate macrocapsule, with a reasonable expectation of success in obtaining a composition suitable for transplant of pancreatic islets because it was known from Dufrane that neonatal pig islets and adult pig islets are suitable of transplantation using gelled alginate as a substrate. The selection of a known material suitable for its intended purpose supports obviousness and combining prior art elements according to known methods to obtain predictable results supports obviousness.
Claims 13-15 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Desai and Furusako as applied to claims 1-8, 16, 17, and 19 above, and further in view of Kauper (US 2015/0073381 Published March 12, 2015).
The claims further define the device by the presence of a semipermeable membrane.
The teachings of Desai and Furusako are relied upon as described above, however they do not teach a semipermeable membrane encapsulating the macrocapsule.
The teachings of Kauper are related to encapsulated cell therapy device for delivering biologically active molecules (Abstract). Active molecules include hormones (paragraph 0007). The device may be implanted into any part of the body (paragraph 0022). The device comprises a semi-permeable membrane made from a permselective, immunoisolatory membrane. For example, the semi-permeable membranes are made from an ultrafiltration membrane or a microfiltration membrane (paragraph 0023). In still other embodiments, the semi-permeable membrane may be made from any biocompatible material selected from cellulose acetates (paragraph 0024). The device may be used for treated metabolic disorders (paragraph 0030). Also provided are methods of delivering one or more biologically active molecules to a recipient host by implanting any of the implantable cell culture devices described herein into a target region of the recipient host, wherein the one or more encapsulated cells or cell lines (e.g., ARPE-19 cells) secrete the biologically active molecules at the target region (paragraph 0036). The surrounding semi-permeable membrane is a permselective, immunoprotective membrane. That is, it protects cells in the core from the immune system of the individual in whom the device is implanted. It does so (1) by preventing harmful substances of the individual's body from entering the core, (2) by minimizing contact between the individual and inflammatory, antigenic, or otherwise harmful materials which may be present in the core and (3) by providing a spatial and physical barrier sufficient to prevent immunological contact between the isolated moiety and detrimental portions of the individual's immune system (paragraph 0098).
The teachings of Kauper and Desai modified by Furusako are related to transplant devices comprising encapsulate cells intended for treating metabolic disorders, and it would have been obvious to have combined them because they are in the same field of endeavor. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified Desai’s system by enclosing the macrocapsule with a semipermeable membrane made from cellulose acetate in order to protect cells in the core from the immune system of the individual in whom the device is implanted. One of skill would have been motivated to do so because Kauper teaches that it does so (1) by preventing harmful substances of the individual's body from entering the core, (2) by minimizing contact between the individual and inflammatory, antigenic, or otherwise harmful materials which may be present in the core and (3) by providing a spatial and physical barrier sufficient to prevent immunological contact between the isolated moiety and detrimental portions of the individual's immune system. This modification of Desai would have been obvious in view of Desai’s teachings on page 22, which suggest optionally applying a semi-permanent membrane of an immunoprotective material to the surface of cell-containing microcapsules that are encapsulated by the macrocapsule.
Double Patenting Rejections
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 1-8 and 10-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 7-17, 19-26, 28, 29, and 35 of copending Application No. 17/620,918 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims and copending claims are drawn to a transplantation device that overlap in scope. Copending claims require a transplantation device comprising cells enclosed in a hydrogel, wherein the hydrogel is formed from alginic acid derivatives of formulae I and II, which meet the requirements of the elected species of alginic acid derivatives of formulae I and II. Cells include pancreatic islet cells of adult pig or neonatal pig. The hydrogel is further encapsulated in a semipermeable membrane that is a dialysis membrane formed from cellulose acetate. Copending claims 14-17 describe dimensions of the hydrogel, which renders the claimed hydrogel thickness and surface area obvious because it would have been obvious to modify the hydrogel and form it in a size and shape suitable for use as a transplantation device. The specification was reviewed and there is no evidence that the claimed dimensions are critical.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617
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