DETAILED ACTION
Claims 1-2, 4, 8, 10, 13, 20, 28-29, 32, 36, 43-44, 46, 48-49, 55, 58, 67-69, 88 and 108-113 are currently pending. Claims 1-2, 4, 13, 20, 28-29, 32, 36, 43-44, 46, 48-49, 55, 68-69 and 108 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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 01/08/2026 is acknowledged. The traversal is on the ground(s) that a combined search and examination of the alleged invention would not be a serious burden. This is not found persuasive because the instant application is a national stage entry application and thus is restricted under unity of invention requirements. The special technical feature does not make a contribution over the prior art, US 8,691,543.
The requirement is still deemed proper and is therefore made FINAL.
Claims 88 and 109-113 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/08/2026. It is noted that claim 88 is properly placed in Group III. Newly added claims 109-113 are dependent on claim 88 and thus properly placed in withdrawn Group III.
Applicant’s election of nanofibrous polyurethane, polyethylene terephthalate and polybutylene terephthalate, tacrolimus, cell secretion and Crohn’s disease of an antibody in the reply filed on 01/08/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 8, 10, 58 and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/08/2026.
Priority
The instant application is a national stage entry of PCT/US21/22994, filed 03/18/2021, which claims priority to provisional application 62/991,422, filed 03/18/2020.
Information Disclosure Statement
No Information Disclosure Statement has been filed in the instant application. Applicants are reminded of their duty to disclose all information known to them to be material to patentability as defined in 37 C.F.R. 1.56.
Claim Rejections - 35 USC § 112
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.
Claim 36 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 36 recites the limitation "the membrane" in first line. There is insufficient antecedent basis for this limitation in the claim. Claim 28, from which it depends, contains limitations directed to a porous membrane, however does not have a limitation directed to “the membrane pores”, and thus lacks antecedent bases.
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, 4, 20, 43-44, 49 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 2011/0142804.
Regarding claim 1 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).
Regarding claim 4, the limitation of wherein the inner layer comprises at least one of nanofibrous polyurethane is met by Wang teaching nanofiber polyurethane (abstract).
Regarding claim 20, 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, 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 the outer layer comprises a nanofibrous polymer (claim 1).
Wang does not specifically teach the device comprises a total thickness of 250 um or less (claim 44).
Wang does not specifically teach wherein the cells secrete an antibody (claim 55)
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 nanofiber sizes for the PET mesh taught by Wang as the ‘804 publication teaches PET scaffolds wherein the fibers may be nano or micro sized, thus providing an expectation of success in using PET nanosized fibers to form the mesh in Wang. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use nanofibers in the PET mesh teaches by Wang as Wang teaches the desire for nanosized fibers including minimal macrophage responses in vitro and in vivo and induced only mild foreign body reactions. 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.
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 cells which secrete antibodies in the device taught by Wang as Wang teaches the inclusion of cells in the device and the ‘804 publication teaches specifically the use of cells which release antibodies wherein Wang and the ‘804 publication are both directed to porous device which are to be implanted with the cell remaining in the implant.
Claim(s) 2, 13, 28-29, 32, 46 and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang and US 2011/0142804 as applied to claims 1, 4, 20, 43-44, 49 and 55 above, and further in view of US 2017/0030011 and US 2016/0310541.
As mentioned in the above 103 rejection, all of the limitations of claims 1, 4, 20, 43-44, 49 and 55 are taught by the combination of Wang and the ‘804 publication.
Regarding claims 48 and 108, the limitation of outer layer comprising nanofibrous polyethylene terephthalate and an inner layer comprising nanofibrous polyurethane, wherein the out layer and the inner layer comprise nanopore shaving a diameter of 1 um or less 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). 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). The pores are taught to be sized to keep the cells within the containers [0008]. The device is taught to have multiple layers and 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]. 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].
The combination of references does not specifically teach nanofibrous polyethylene terephthalate and polybutylene terephthalate (claim 2 and 48).
The ‘011 publication teaches tuning surface properties of melt blown polyester fibers (title)wherein the polyester based fibers include PBT fiber (abstract). The polyester fiber mat is taught to include PB and optionally poly(ethylene terephthalate (PET). Polyester fiber mat can comprise PBT and PEB blends wherein the amount of PET in a range ([0009], [0030]).
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 derform, 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]. 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]).
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 a combination of PBT and PET to form a fibrous composition as the ‘011 publication teaches PBT and PET to both be polyesters used in medical devices [0002] and Wang is directed to a PET mesh used to form a medical device. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use a combination of PBT and PET to form the mesh of Wang as the ‘011 publication teaches being able to tune properties of the polyester fibers (abstract). One of ordinary skill in the art before the filing date of the claimed invention would be motivated and have an expectation of success as the ‘541 publication teaches that is known to use combinations of PBT and PET to form fibers for a cell chamber and Wang is taught to be a cell chamber device comprising PET fibers.
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 use multiple layers or the PET mesh and PU nanoporous matrix as taught by Wang to form the cell encapsulating device as the ‘541 publication teaches using multiple layers to obtain the desired cell encapsulating device. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use multiple layers of the PET mesh and PU-nanoporous matrix as the ‘541 publication teaches the use of more than one layer to obtain the desired reinforcement of the membrane and increase the rigidity of the structure. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use the nanofiber PU matrix on either side of the PET mesh taught by Wang as the ‘541 publication teaches alternating layers to form the desired cell implant and Wang teaches the benefits of the nanofiber PU matrix including minimal macrophage response and film forging body reaction using the PU nanofibers.
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 amount 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”.
Claim(s) 68-69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang and US 2011/0142804 as applied to claims 1, 4, 20, 43-44, 49 and 55 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, 4, 20, 43-44, 49 and 55 are taught by the combination of Wang and the ‘804 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).
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 cells releasing VZD in the cell chamber taught by the combination of references as the ‘804 publication teaches the cell chambers to encapsulate cells that produce therapeutic factors such as antibodies 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 ‘804 publication teaches the desire to utilize cells types with release therapeutic factors such as antibodies 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.
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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