FINAL 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 .
Status of Claims
Receipt is acknowledged of the claim amendments filed on 25 February 2025.
Claims 1, 6 and 34 have been amended.
Claims 2-5 and 7-8 are cancelled.
Claims 35-39 have been added.
Claims 19, 24 and 32 remains withdrawn from consideration.
Claims 1, 6, 9-18, 20-23, 25-29, 30-31 and 34-39 are presented for examination herein to the extent that the therapeutic agent is insulin and the preparation of cells are islet cells, e.g., applicant’s elected species.
New Grounds of Rejection Necessitated by the Claim Amendments
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.
Claims 37 and 39 are 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.
Claims 37 and 39 recite “nanofibers of the nanofibrous substrate comprise a fiber diameter of 270 nm, and has an average thickness of 100 µm” (emphasis added), which renders claims 37 and 39 indefinite because nanofiber diameter should be about the same as average thickness of the nanofiber. It seems like applicant meant for the average thickness to be in reference to the nanofibrous substrate and not the nanofibers. In favor of compact prosecution, the recitation of “and has an average thickness of 100 µm” is interpreted as referring to the nanofibrous substrate average thickness and not the nanofiber.
Rejections Maintained and Modified as Necessitated by the 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 6, 9-18, 20-23, 25-28, 30-31 and 34-39 are rejected under 35 U.S.C. 103 as being unpatentable over MCKEAN (WO 2020/070484 A1, publication date of 09 April 2020).
McKean is primarily directed towards a therapeutic composition comprising an inner portion and a biocompatible membrane fully or partially surrounding the inner portion (abstract).
Regarding claims 1, 6, 13-18, 20, 23, 25 and 34-35, McKean discloses a membrane (e.g., substrate with interior wall) comprising pores of a suitable size such as to allow the passage of solute molecules such as glucose but prevent the passage of larger particles including cells (page 2, lines 10-12). McKean discloses that the membrane encapsulate a therapeutic agent including fully (page 2, lines 17-18 and lines 23-25). McKean discloses that the membrane comprises layers including non-woven network of thermoplastic polyurethane polymer fibers formed by electrospinning and having an average pore diameter of less than 5 µm (page 2, lines 25-29). McKean discloses a carrier disposed within the inner portion (e.g., core) and the therapeutic agent is disposed in the carrier including encapsulated within the carrier (page 3, lines 22-26; page 4, line 3; Figure 3). McKean discloses that the carrier includes a hydrogel (page 4, lines 22-23). McKean discloses that the layers can be made by polyurethane polymers (e.g., a single non-woven nanofiber material for multilayers) (page 6, lines 15-25). McKean discloses that the fibers are nanofibers and the mean diameter of the polymer fibers in the membrane is less than 1000nm and most preferably including 100-500 nm (page 13, lines 20-24). McKean discloses that the polymer fibers of the first layer (e.g., elongated nanofibrous substrate) has a mean diameter of ranging from 50-500nm (paragraph bridging pages 32 and 33). McKean discloses that the composition can be implanted into a human (page 17, line 17-18). McKean discloses that the composition is elongated and can be cylinder-shaped (e.g., elongated nanofibrous substrate having sealed proximal and distal ends, with same fiber diameter and same fiber density across the substrate except at the sealed proximal and distal ends) (page 17, lines 21-22). McKean discloses the material constituting a pouch or bag forms the outer boundary of the environment in which the intended contents can be placed, precluding the ingress and egress of the intended contents from points other than the intended entrance and exit of the pouch or bag. McKean discloses that the entrance and exit are sealed to wholly surround the innards of the pouch or bag (page 12, lines 21-27; page 24, lines 7-9). McKean discloses that the therapeutic agent includes pancreatic cells and further including cells and further include islet of Langerhans (paragraph bridging pages 23 and 24). McKean discloses that the membrane is formed by electrospinning (page 25, line 18). McKean discloses that the polymer fibers can comprise a single layer of fibers or multiple layers and that the porosity of the layers and the pore size within each layer may be the same (e.g., same fiber density across substrate) (page 25, lines 25-27). McKean discloses that the electrospinning process provides a uniform deposition of material (e.g., same fiber diameter and same fiber density) (page 28, lines 1-10; page 29, lines 12-14). Figure 2 of McKean shows a bottom layer with a fiber diameter of 600 nm (page 34, line 32) that was created by electrospinning (Example 1 of McKean), where the pores are substantially uniformly dispersed on the layer (e.g., same fiber diameter and same fiber density) (Figure 2 of McKean).
Regarding claims 9-12, McKean discloses that the membrane comprises layers including non-woven network of thermoplastic polyurethane polymer fibers formed by electrospinning and having an average pore diameter of less than 5 µm (page 2, lines 25-29). McKean discloses that the thermoplastic polyurethane includes Silicone-Polycarbonate-urethane (page 15, lines 22-23). Therefore, the composition of McKean that comprises a membrane comprising a layer of non-woven network of thermoplastic polyurethane polymer fibers formed by electrospinning and having an average pore diameter of less than 5 µm; wherein the thermoplastic polyurethane is Silicone-Polycarbonate-urethane; is substantially the same as the instantly claimed composition, therefore, the composition of McKean that comprises a membrane comprising a layer of non-woven network of thermoplastic polyurethane polymer fibers formed by electrospinning and having an average pore diameter of less than 5 µm; wherein the thermoplastic polyurethane is Silicone-Polycarbonate-urethane; would necessarily have the same characteristics, e.g., rupture strain of ≥ 2, elastically deformable up to about 5 MPa under a 0.5 strain, has an ultimate tensile strength of up to about 15 MPa under a 0.5 strain, has an ultimate tensile strength of up to ab out 15 MPa under a strain of greater than 2, and has a Young’s modulus of about 12.6 MPa when calculated from 10-20% of its stress-strain curve, especially in the absence of evidence to the contrary.
Regarding claims 21-22, McKean discloses that the therapeutic agent includes islet of Langerhans (e.g., islet cells/Beta cells) (paragraph bridging pages 23 and 24) and McKean discloses that Beta cells are responsible for regulating blood sugar (glucose) levels by producing precise insulin to survive (page, lines 21-23). Therefore, the islet of Langerhans (e.g., islet cells/Beta cells) disclosed by McKean necessarily secretes insulin.
Regarding claims 26-27, McKean discloses that the amount of the cell at least 1000 cells (page 23, lines 22-25; page 37).
Regarding claim 28, McKean discloses that one or more additives are disposed within the carrier and the additives a selected from including growth actors and cytokines (page 5, lines 20-23; page 22, line 23; page 23, line 2). McKean discloses that other actives can be included including a nucleic acid, a protein, a polypeptide and an antibody (page 19, lines 16-19).
Regarding claim 30, McKean discloses that the carrier material is including alginate (page 16, lines 15-17).
Regarding claim 31, McKean discloses that the diameter of a cylinder-shaped (e.g., tube) includes about from 200 µm to about 500 µm (e.g., about .5 mm) (page 23, lines 33-35). McKean discloses that the diameter of the cylinder includes 2mm to 5 cm (page 18, lines 7-8).
Regarding claims 36-39, McKean discloses that the membrane has a thickness in the range 25 to 250 µm (page 14, lines 6-7). McKean discloses that the polymer fibers can comprise a single layer of fibers or multiple layers and that the porosity of the layers and the pore size within each layer may be the same (e.g., same fiber density across substrate) (page 25, lines 25-27). McKean discloses that the electrospinning process provides a uniform deposition of material (e.g., same fiber diameter and same fiber density) (page 28, lines 1-10; page 29, lines 12-14). McKean discloses that the membrane can comprise 1 layer and that the thickness of the membrane is from about 30 µm to about 1000 µm (page 27, lines 14-18).
Regarding claims 37 and 39, McKean discloses that the mean diameter of the polymer fibres in the membrane is most preferably in the range of including 50-500 nm (page 13, lines 22-24).
Although, McKean discloses substantially the same composition, where including the inner portion can be alginate (e.g., hydrogel) the therapeutic can be an islet cell, and that the shape of the composition includes a cylinder, McKean did not specifically teach a single composition that includes all of the limitations together, therefore, this rejection is made under 35 U.S.C. 103. It would have been prima facie obvious at the time the invention was made to produce a cylinder shaped composition that comprises a fully encapsulating membrane that comprises a single layer or multiple layers of a porous, non-woven network of thermoplastic polyurethane polymer fibers (e.g., elongated nanofibrous substrate having sealed proximal and distal ends, with same fiber diameter and same fiber density across the substrate except at the sealed proximal and distal ends) formed by electrospinning and having an average pore diameter of less than 5 µm, a carrier in an inner portion, a therapeutic agent disposed in the carrier; wherein the fibers are nanofibers having a mean diameter of including 100-500 nm; wherein the carrier is including alginate (e.g., hydrogel); and wherein the therapeutic agent is including islet cell. The person of ordinary skill in the art would have been motivated to make those modifications because McKean teaches that the carrier includes alginate, the therapeutic includes islet cell and the entrance and exit are sealed to wholly surround the innards of the composition. The person of ordinary skill in the art would have reasonably expected success because McKean discloses a membrane (e.g., substrate with interior wall) comprising pores of a suitable size such as to allow the passage of solute molecules such as glucose but prevent the passage of larger particles including cells (page 2, lines 10-12). McKean discloses that the membrane encapsulate a therapeutic agent (page 2, lines 17-18). McKean discloses that the membrane comprises layers including non-woven network of thermoplastic polyurethane polymer fibers formed by electrospinning and having an average pore diameter of less than 5 µm (page 2, lines 25-29). McKean discloses a carrier disposed within the inner portion (e.g., core) and the therapeutic agent is disposed in the carrier including encapsulated within the carrier (page 3, lines 22-26; page 4, line 3; Figure 3). McKean discloses that the carrier includes a hydrogel (page 4, lines 22-23). McKean discloses that the fibers are nanofibers and the mean diameter of the polymer fibers in the membrane is less than 1000nm and most preferably including 100-500 nm (page 13, lines 20-24). McKean discloses that the polymer fibers of the first layer has a mean diameter of ranging from 50-500nm (paragraph bridging pages 32 and 33). McKean discloses that the composition can be implanted into a human (e.g., implantable) (page 17, line 17-18). McKean discloses that the composition is elongated and can be cylinder-shaped (e.g., having proximal and distal ends) (page 17, lines 21-22). McKean discloses that the therapeutic agent includes pancreatic cells and further including cells and further include islet of Langerhans (paragraph bridging pages 23 and 24). McKean discloses the material constituting a pouch or bag forms the outer boundary of the environment in which the intended contents can be placed, precluding the ingress and egress of the intended contents from points other than the intended entrance and exit of the pouch or bag. McKean discloses that the entrance and exit are sealed to wholly surround the innards of the pouch or bag (page 12, lines 21-27). Figure 2 of McKean shows a bottom layer with a fiber diameter of 600 nm (e.g., elongated nanofibrous substrate) (page 34, line 32) that was created by electrospinning (Example 1 of McKean), where the pores are substantially uniformly dispersed on the layer (e.g., uniform porosity) (Figure 2 of McKean).
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over McKean as applied to claims 1, 6, 9-18, 20-23, 25-28, 30-31 and 34-39 above, and further in view of AHN (WO 2015/191547 A1, publication date of 17 December 2015).
Regarding claim 29, the teachings of claims 1 and 28 are described above in section 8
McKean does not specifically teach that the active in the carrier is an anti-inflammatory agent. The deficiency is made up for by the teachings of Ahn.
Ahn is primarily directed towards an implantable therapeutic delivery system (abstract).
Regarding claim 29, Ahn teaches transplanted biomedical devices can cause foreign body reactions and influence fibrosis (paragraph [0009]). Ahn teaches including one or more biologically reactive reagents including anti-inflammatory reagents to mitigate any host immune system inflammatory response and fibrosis (paragraph [0072]). Ahn teaches that anti-inflammatory reagents include diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, and tolmetin), analgesics (e.g., acetaminophen, oxycodone and tramadol (paragraph [0067]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a cylinder shaped composition that comprises a fully encapsulating membrane that comprises a single layer or multiple layers of a porous, non-woven network of thermoplastic polyurethane polymer fibers (e.g., elongated nanofibrous substrate having sealed proximal and distal ends, with same fiber diameter and same fiber density across the substrate except at the sealed proximal and distal ends) formed by electrospinning and having an average pore diameter of less than 5 µm, a carrier in an inner portion, a therapeutic agent disposed in the carrier; wherein the fibers are nanofibers having a mean diameter of including 100-500 nm; wherein the carrier is including alginate (e.g., hydrogel); and wherein the therapeutic agent is including islet cell; and wherein the carrier further comprises an anti-inflammatory reagent selected from including diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, and tolmetin), analgesics (e.g. , acetaminophen, oxycodone and tramadol). The person of ordinary skill in the art would have been motivated to make those modifications to obtain an implantable composition that is able to mitigate any host immune system inflammatory response and fibrosis which can occur with implants by including anti-inflammatory agents selected from including diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, and tolmetin), analgesics (e.g. , acetaminophen, oxycodone and tramadol), as taught by Ahn. The person of ordinary skill in the art would have reasonably would have expected success because Ahn teaches transplanted biomedical devices can cause foreign body reactions and influence fibrosis (paragraph [0009]). Ahn teaches including one or more biologically reactive reagents including anti-inflammatory reagents to mitigate any host immune system inflammatory response and fibrosis (paragraph [0072]). Ahn teaches that anti-inflammatory reagents include diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, salsalate, sulindac, and tolmetin), analgesics (e.g. , acetaminophen, oxycodone and tramadol (paragraph [0067]).
Therefore, the claimed 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, because every element of the invention has been collectively taught by the combined teachings of the references.
Response to Arguments
Applicant argues that McKean is silent as to the pore diameter and does not provide any features, such as porosity or fiber diameter for the single layer. Applicant argues that McKean only explicitly describes a biocompatible membrane with a first layer and second layer that have different fiber properties and porosity. Applicant argues that the examples of McKean have two or more layers. Applicant argues that the office is picking and choosing form disparate teachings of the reference and fails to show why a person of ordinary skill in the art would have been motivated to modify the bilayer membrane of McKean, where the two layers have different fiber properties and porosity to produce the elongated nanofibrous substrate instantly claimed.
Applicant's arguments filed on 25 February 2025 have been fully considered but they are not persuasive. In response, McKean discloses a biocompatible membrane which comprises pores of a suitable size to allow the passage of solute molecules but prevent the passage of larger particles such as cells (page 2, lines 8-12). McKean discloses that the network of polymer fibres can comprise a single layer of fibres (page 25, line 25). McKean discloses that the membrane has a thickness in the range 25 to 250 µm (page 14, lines 6-7). McKean discloses that pore size of including less than 5 µm can prevent the passage of cells (page 14, lines 27-30). McKean discloses that the polymer fibers can comprise a single layer of fibers or multiple layers and that the porosity of the layers and the pore size within each layer may be the same (e.g., same fiber density across substrate) (page 25, lines 25-27). McKean discloses that the electrospinning process provides a uniform deposition of material (e.g., same fiber diameter and same fiber density) (page 28, lines 1-10; page 29, lines 12-14). McKean discloses that the membrane can comprise 1 layer and that the thickness of the membrane is from about 30 µm to about 1000 µm (page 27, lines 14-18). Therefore, it would have been prima facie obvious for one of ordinary skill in the art to produce a composition with a single layer of polymer fibres because McKean teaches including single layer of polymer fibres and used the ranges of pore size and membrane thickness disclosed by McKean (thickness of the membrane is from about 30 µm to about 1000 µm and pore mean diameter of including 100-500 nm) to optimize in order to obtain a single layer membrane that allow the passage of solute molecules but prevent the passage of cells.
Thus, for the reasons of record and for the reasons presented above claims 1, 6, 9-18, 20-23, 25-29, 30-31 and 34-39 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
THIS ACTION IS MADE FINAL.
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 extension fee 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 date of this final action.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600