DETAILED ACTION
Claims 1, 8, 10, 13, 20, 28-29, 32, 36, 43-44, 46, 48-49, 55, 67-69, 88, 108-115 are currently pending. Claims 1, 13, 20, 28-29, 32, 36, 43-44, 46, 48-49, 55, 68-69, 108, 114-115 are currently under examination.
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 .
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 07/13/2026 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Withdrawn Rejections
The prior rejection of claim 36 under 112(b) is withdrawn in light of Applicant amending the dependency of claim 36 to correct antecedent basis.
The prior rejection of claim(s) 1, 4, 20, 43-44, 49 and 55 under 35 U.S.C. 103 as being unpatentable over Wang in view of US 2011/0142804 is withdrawn in light of Applicant amending the instant claims to specify the outer layer is a mixture of electrospun PET and PBT, which Wang and the ‘804 publication does not teach.
Examiner’s Note
Applicant's amendments and arguments filed 07/22/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 07/22/2026, it is noted that claims 1, 28, 36 and 48 have been amended, claims 114-115 are newly added. No new matter or claims have been added.
New Rejections:
The following rejections are newly applied based on Applicant’s claim amendments.
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.
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.
Claim(s) 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, Kai, et al., Biomaterials 102 (2016) pgs. 249-258) in view of US 2012/0068384.
Regarding claims 1 and 48, the limitation of a device comprising a multilayer scaffold surrounding a cell chamber, wherein the multilayer scaffold comprises an outer layer and an inner layer in contact with the cell chamber and wherein the outer layer and the inner layer each comprise a nonfibrous polymer is met by Wang teaching an implantable membrane which encapsulated cells. The electrospun membranes based on polyurethane were fabricated to containing nanofibers. PU-nano caused minimal macrophage responses in vitro and in vivo and induced only mild foreign body reactions (abstract). PET mesh is taught as an outer layer with electrospun nanofiber polyurethane inner layer (Figure 1). The device comprises two PU nanomembranes placed between two polyethylene terephthalate (PET) meshes to provide mechanical support, the membranes were welded together and the final device was circular and had an internal volume of 30 ul (page 254, second column, first paragraph). Wang teaching nanofiber polyurethane (abstract).
Regarding claims 20, 32, 36, 48 and 114, the limitation of wherein the inner layer comprises pores wherein the pores are sized to permit the passage of biomolecules is met by Wang teaching the pore size of the nano-PU is 0.48 um which is used for transport of proteins but is a barrier for cells (page 252, first column, second paragraph).
Regarding claim 43, the limitation of further comprising a loading port to permit the loading of cells into the cell chamber is met by Wang teaching a polyethylene tube positioned between the membranes as port (Section 2.4).
Regarding claim 49 and 108, the limitation of wherein the cells chamber comprises cells is met by Wang teaching cells loaded into the encapsulation device (page 254, second column, first and second paragraph).
Wang does not specifically teach wherein the outer layer comprises a mixture of electrospun polyethylene terephthalate and polybutylene terephthalate, wherein the outer layer is nanofibrous polymer (claim 1).
The ‘384 publication teaches a bioactive nanofibrous material constructed which is manufactured using electrospinning methods. The textile is taught to be formed of a non-biodegradable polymer, an active agent and a carrier (abstract). PET is taught to be electrospun and nanofibrous size [0018]. The electrospinning perfusion method yields a fabricated textile which may be folded, twisted or otherwise manipulated to meet the specific requirement of thickness, gauge or deniers and may be tailed to form to particular shapes [0031]. The fibers are taught to be nanometer size, less than 2 microns [0032]. Polymeric material to form the fibers is taught to include polyethylene terephthalate, polybutylene terephthalate and polyurethane and mixtures thereof (Table 1). The nanofibrous structure is taught to enhance in vivo biocompatibility [0048]. The active agent is taught to be effective against tumors or avoid blood coagulation [0056]. The nanofibrous composite is flexible, strong and durable [0077]. The textile may be a single layer of fibrous matter or exist as multiple and different deniers of fibers which are present in a range of thickness and configurations [0035], thus reading on multiple layers of PET porous membrane claims 28-29.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use PET/PBT electrospun nanofibers to form the outer as Wang teaches the outer layer to be formed of PET Mesh and teaches the benefits of nanofibrous electrospun membranes to include immune barrier for cell transplantation. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use PET/PBT nanofiber electropunk membrane as taught by the ‘384 publication as the ‘384 publication teaches mixtures of PET/PBT may be used to form membranes and wherein the electrospun nanofibrous membrane has the desirable properties of being tailored to obtain the desired thickness and shape and is flexible , strong and durable, thus motivating one of ordinary skill in the art to use the electrospun nanofibers to form the outer layer taught by Wang. One of ordinary skill in the art would have a reasonable expectation of success as Wang teaches the use of PET to form the outer layer and teaches the benefits of electrospun nanofibers and the ‘384 publication teaches electrospun PET/PBT nanofibers forming a matrix for implantation. It would have been obvious to one of ordinary skill in the art before the filing date of the claimed inventions to use multiple layers of the electrospun fibers as the ‘384 publication teaches the electrospun the membrane formed maybe a single layer or multiple, thus teaching it was known in the art to use different layers of different fibers to obtain the desired membrane.
Claim(s) 13, 46 and 55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, Kai, et al., Biomaterials 102 (2016) pgs. 249-258) in view of US 2012/0068384 as applied to claims 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 above, and further in view of US 2016/0310541 (previously applied).
As mentioned in the above 103 rejection, all of the limitations of claims 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 are taught by the combination of Wang and the ‘384 publication.
The combination of references does not specifically teach wherein the outer layer and/or the inner layer comprises an anti-inflammatory agent selected from the group including tacrolimus (claim 13).
The ‘541 publication teaches chamber for encapsulating secreting cells (title). The non-woven polymer is taught to be formed of fibers which may be formed of polyesters such as PET, PBT and blends of these polymers [0024]. The ‘541 publication teaches mixing active agent with hydrophilic polymers intended to release the medium surrounding the semipermeable membrane in order to reduce inflammation wherein the active agent includes anti-inflammatory agents such as tacrolimus ([0080]-[0084]). The polyester is taught to be a membrane is taught to be hydrophilic ([0043], [0053]). The ‘541 publication teaches membrane comprises two layers of porous biocompatible polymer on either side of the layer of biocompatible non-woven polymer. The biocompatible non-woven polymer is situated between two layers of porous biocompatible polymer. This makes it possible to optimize the strength of the device. The layer of non-woven can be consider to behave like a sponge with gives the compatibility to absorb impacts and to deform, thus increasing the rigidity of the membrane in situ. The layer of non-woven between two porous layers make it possible to prevent aggregation of cells while at the same time providing the device with additional protection/and strength [0030]-[0031]. The porous layer is taught to include PET, polyester ([0034], [0035]). The diffusion substance is taught to pass through each layer [0052] wherein the cells are taught to expression an active substance of issue including peptides [0131]. Reinforcement of the membrane may be improved via a multilayer system alternating layers of woven or non-woven polymers and of porous polymers [0078]. The ‘541 publication teaches encapsulating a large number of cells in order to have prolonged physiological effect after implantation ([0014], [0122]), thus teaching an optimizable parameter.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to include tacrolimus in the scaffold taught by Wang because the ‘541 publication teaches tacrolimus being used for an anti-inflammatory agent in a cell encapsulated chamber wherein the membrane material is taught to include tacrolimus to be used as an anti-inflammatory agent wherein inflammation is taught to be desired to be avoided [0019].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to encapsulate a large number of cells in the device of Wang as Wang teaches encapsulating cells and the ‘541 publication teaches encapsulating a large number of cells optionally up to one million islets with number of cells being caried according the desired amount of implant in the patient, thus teaching encapsulation number of cells to be an optimizable parameter. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the cells releasing anti-inflammatory agents as taught by the ‘541 publication in the device of Wang as the ‘541 publication teaches the desire to use cells releasing anti-inflammatory agents in cell chambers and Wang teaches cell chambers.
Claim(s) 68-69 and 115 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, Kai, et al., Biomaterials 102 (2016) pgs. 249-258) in view of US 2012/0068384 and US 2016/0310541 as applied to claims 1, 13, 20, 28-29, 32, 36, 43, 46, 48-49, 55, 108 and 114 above, and further in view of Wyant (Wyant, Tim, et al., mABs (2013) 5:6 pgs. 842-850).
As mentioned in the above 103 rejection, all of the limitations of claims 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 are taught by the combination of Wang and the ‘384 publication.
Wyant teaches Vedolizumab is a humanized monoclonal antibody in development for the treatment of inflammatory bowel disease. VDZ binds alpha4beta7 integrin complex and inhibits its binding to mucosal addressing cell adhesion molecue-1-, thus preventing lymphocyte extravasation to gut mucosal tissues (abstract). VDZis an antibody currently in development for the treatment of ulcerative colitis and Crohn’s disease. VDZ is taught to specifically bind to alpha4beta7integrin with high affinity (page 844, second column) an may be internalized in cells (page 847, second column). Mabs are an important part of the physician’s treatment of many autoimmune and oncologic diseases. VDZ is humanized IgG1 antibody in devolvement for the treatment of ulcerative colitis and Crohn’s disease. It has shown to be tolerable and to provide benefit in Phase 1 and Phase 3 clinical trials (page 847, first column). The cells are taught to be ACT-1 (abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use ACT-1 cells releasing VZD in the cell chamber taught by the combination of references as the ‘541 publication teaches the cell chambers to encapsulate cells that produce therapeutic factors and VZD is an antibody. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use VZD as Wyant teaches VZD to be used to treat diseases such as ulcerative colitis and Chron’s disease and ‘541 publication teaches the desire to utilize cells types with release therapeutic factors and Wang teaches the desire for implanted diseases to treat autoimmune disease (page 255, first column) and Wyant teaches VZD as a treatment of autoimmune disease such as Chron’s disease.
Claim(s) 44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang (Wang, Kai, et al., Biomaterials 102 (2016) pgs. 249-258) in view of US 2012/0068384 as applied to claims 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 above, and further in view of US 2011/0142804 (previously applied).
As mentioned in the above 103 rejection, all of the limitations of claims 1, 20, 28-29, 32, 36, 43, 48-49, 108 and 114 are taught by the combination of Wang and the ‘384 publication.
The ‘804 publication teaches a device to prevent migration of Human Mesenchymal Stem Cells from a delivery site while allowing communication between the stem cells and native cardiomyocytes. The device is characterized by scaffold pore size, fiber diameter and biomaterial selection. The invention includes a two-part polyurethane scaffold (abstract). Cells included are taught to produce antibodies [0006]. The pores are taught to be sized to keep the cells within the containers [0008]. The device is taught to have multiple layers an include nanoporous polymer mesh inhibiting cell migration ([0046], claim 5). The scaffold is sized to permit diffusion of cell nutrients and other molecules of important for proper cell function [0049]. Material used for the scaffold include woven nylon (PET) [0050]. The polymer fibers may be nanometer to micrometer size in diameter [0055]. The thickness of the nanofibrous scaffold can be adjusted to a thickness of 10-150 um and pores sized between 0.5 and 10 micrometers [0060].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the scaffold size taught by the ‘804 publication for that of Wang as Wang and the ‘804 publication are both directed to multiple layered fiber containing devices used to deliver cells. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known scaffold thickness as taught by the ‘804 publication for a cell containing implantable device as is taught by Wang and the ‘804 publication.
Response to arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
Applicant argues Wang does not disclose nanofibrous mesh. Applicant argues the ‘804 publication teaches material susceptible to fibrotic encapsulation and infection and that can degrade.
In response, Applicant is referred to the newly applied rejection above wherein the ‘384 publication teaches a bioactive nanofibrous material constructed which is manufactured using electrospinning methods, PET is taught to be electrospun and nanofibrous size [0018] wherein polymeric material to form the fibers is taught to include polyethylene terephthalate, polybutylene terephthalate and polyurethane and mixtures thereof (Table 1). The nanofibrous structure is taught to enhance in vivo biocompatibility [0048]. It is further noted that the ‘804 publication specifically claims the use of a device formed from nanofibrous dacron (claims 1-3).
Applicant argues Wyant fails to cure the deficiencies of Wang. Additionally, it does not give any expectation of success that the chambers can house cells secreting vedolizumab in a way that they can secrete the antibody when the devices are implanted in vivo.
In response, Applicant’s arguments regarding Wang are addressed above as first presented. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use ACT-1 cells releasing VZD in the cell chamber taught by the combination of references as the ‘541 publication teaches the cell chambers to encapsulate cells that produce therapeutic factors and VZD is an antibody. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use VZD as Wyant teaches VZD to be used to treat diseases such as ulcerative colitis and Chron’s disease and ‘541 publication teaches the desire to utilize cells types with release therapeutic factors and Wang teaches the desire for implanted diseases to treat autoimmune disease (page 255, first column) and Wyant teaches VZD as a treatment of autoimmune disease such as Chron’s disease.
Conclusion
No claims are allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613
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