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 Application
Applicant is advised that the Examiner assigned to this Application has changed. The Examiner currently assigned to this Application is Aradhana Sasan, whose contact information can be found at the end of this action. Applicant is further advised that this Application is currently assigned to Art Unit 1615.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9 and 16-18) and the species of beta cell as the cell; collagen as the protein; and polysaccharide including carboxymethyl cellulose as the microporous scaffold in the reply filed on 10/08/25 is acknowledged.
The restriction requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 10 and 12-15 were previously cancelled.
New claim 20 was added on 10/08/25.
Claims 1-9, 11, and 16-20 are pending.
Claims 11 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-9, 16-18, and new claim 20 (which depends on claim 9) are included in the prosecution.
Priority
This Application is a CON of PCT/EP 2020/075278 filed on 09/10/20. This Application also claims foreign priority to EP 19382785.4 filed on 09/10/19. Receipt is acknowledged of certified copies of papers submitted under 35 U.S.C. 119 (a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/13/22 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the examiner is considering the information disclosure statement.
Please see the attached copy of PTO-1449.
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 6 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 pre-AIA the applicant regards as the invention.
Claim 6 recites the limitation "wherein the porous size" in lines 1-2. Claim 6 is dependent on claim 1, but claim 1 does not recite any pores or porous limitation. There is insufficient antecedent basis for this limitation in the claim.
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 1-9 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (US 2014/0271843 A1 – “Ma”) in view of Lee et al. (International Journal of Biological Macromolecules 110 (2018) 497-503 – “Lee”).
Instant claim 1 is drawn to a hydrogel capsule comprising:
a cell;
a protein; and
a cross-linking agent;
wherein the cell is within a first core layer comprising the protein;
wherein the first core layer is surrounded by a second layer comprising the protein and the cross-linking agent; and
wherein the cross-linking agent is tannic acid.
Ma teaches multi-layer hydrogel capsules for encapsulation of cells and cell aggregates (Title and Abstract). The hydrogel capsules encapsulating cells consist of three layers, a first an inner acellular core layer, a second hydrogel layer containing cells to be transplanted selected from the group consisting of mammalian secretory, metabolic and structural cells and aggregates thereof, and an outer acellular barrier or structural layer (claim 1). “FIG. 1 is an illustration of a tri-layer capsule, with the cells encapsulated in a core hydrogel and the drug-loaded particles contained in an outer (envelope) hydrogel. An optional membrane material is shown separating the core and envelope hydrogels” ([0020]). Examples of cells for encapsulation include pancreatic islet cells ([0087], [0147]), islet cells include beta cells that secrete insulin and amylin, and in preferred embodiments, a population of islet cells contains at least beta cells ([0037]). Biocompatible polymers for encapsulating cells include collagen ([0041], [0077], [0125], claims 1 and 7).
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Ma does not expressly teach a cross-linking agent and wherein the cross-linking agent is tannic acid.
Lee teaches a tannic acid (TA) cross-linking process for obtaining 3D porous cell-laden collagen structure (Title and Abstract). “Compared to the cell-laden collagen scaffold without TA crosslinking, the scaffold with TA crosslinking was significantly enhanced in mechanical properties, while reasonable cellular activities were observed” (Abstract). Fig. 1 (Page 498) shows the fabrication of cell-laden collagen scaffold, with or without crosslinking with different concentrations of TA, wherein the cells are mouse preosteoblasts MC3T3-E1 (Page 498, section 2.1).
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Lee teaches that from the TA concentration of 0.5 wt% and above, the mechanical strength increased exponentially (Fig. 3a and Page 501, Col. 2, 1st ¶). For T-0.5 and T-1 scaffold, the physical properties were improved, and showed reasonable cellular activities (Page 502, Col. 2, last ¶).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare multi-layer hydrogel capsules for encapsulation of cells, including pancreatic islet cells and beta cells, wherein biocompatible polymers for encapsulating cells include collagen, as taught by Ma, in view of the use of tannic acid for cross-linking cell-laden collagen, as taught by Lee, and produce the instant invention.
One of ordinary skill in the art would have been motivated to add the TA cross-linking agent of Lee in the multi-layer hydrogel collagen capsules of Ma because Lee teaches that the mechanical strength increased exponentially (Fig. 3a and Page 501, Col. 2, 1st ¶), the physical properties were improved, and showed reasonable cellular activities (Page 502, Col. 2, last ¶).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitation of a hydrogel capsule would have been obvious over the multi-layer hydrogel capsules (Title, Abstract, FIG. 1), as taught by Ma.
Regarding instant claim 1, the limitation of a cell would have been obvious over the pancreatic islet cells ([0087], [0147]), and beta cells ([0037]), as taught by Ma.
Regarding instant claim 1, the limitation of a protein would have been obvious over the collagen ([0041], [0077], [0125], claims 1 and 7), as taught by Ma.
Regarding instant claim 1, the limitation of a cross-linking agent which is tannic acid would have been obvious over the TA cross-linking of cell-laden collagen scaffolds (Title, Abstract, Fig. 1, Page 498, section 2.1, Fig. 3a and Page 501, Col. 2, 1st ¶, and Page 502, Col. 2, last ¶), as taught by Lee.
Regarding instant claim 1, the limitation of the cell within a first core layer comprising the protein; wherein the first core layer is surrounded by a second layer comprising the protein and the cross-linking agent would have been obvious over the multi-layer hydrogel capsules (Title, Abstract, FIG. 1), wherein the cells are confined to the core region of the capsules ([0150]), as taught by Ma.
Regarding instant claim 2, the limitation of the protein comprising collagen would have been obvious over the collagen ([0041], [0077], [0125], claims 1 and 7), as taught by Ma.
Regarding instant claim 3, the limitation of the pancreatic cell would have been obvious over the pancreatic islet cells ([0087], [0147]), and beta cells ([0037]), as taught by Ma.
Regarding instant claim 4, the limitation of the elected beta cell would have been obvious over the beta cells ([0037]), as taught by Ma.
Regarding instant claim 5, the limitation of a cell aggregate or an organoid would have been obvious over the cell aggregates ([0016], [0088], [0099], Example 1 – [0131], [0150], Example 2 – [0161], and claim 1), as taught by Ma.
Regarding instant claim 6, the limitation of the porous size of the second layer of the capsule being smaller than 5 µm would have been obvious over the pore size of 5 µm as optimal for vessel regeneration (Page 497, Col. 1, 1st ¶), as taught by Lee. According to MPEP 2144.05(I), “… a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.")”. In the present case, one of ordinary skill in the art would have found it obvious to modify the pore size of the second layer of the capsule based on the optimal cell delivery and stability. The claimed range would have been an obvious variant over the pore size taught by Lee unless there is evidence of criticality or unexpected results.
Regarding instant claim 7, the limitation of a plurality of capsules, wherein the capsules have a mean diameter from 200 µm to 3 mm would have been obvious over the hydrogel capsules encapsulating cells (claim 1) and the overlapping capsule mean diameter range of greater than 1 mm (Abstract, [0128], and claim 2), preferably 1.5 mm or greater ([0017], [0081]), as taught by Ma.
Regarding instant claim 8, the limitation of an implant comprising the hydrogel capsule according to claim 1 would have been obvious over the biocompatible hydrogel capsules encapsulating mammalian cells which have reduced fibrotic overgrowth after implantation in a subject (Abstract, FIGS. 5A and 5B, [0024], [0038], claims 1, 3, 5, 11), as taught by Ma.
Regarding instant claim 8, the limitation of a microporous scaffold would have been obvious over the 3D porous cell-laden collagen scaffolds (Title, Introduction), as taught by Lee.
Regarding instant claim 9, the limitation of the microporous scaffold comprising the elected species of collagen would have been obvious over the 3D porous cell-laden collagen scaffolds (Title, Introduction), as taught by Lee.
Regarding instant claim 16, the limitation of the elected species of protein i.e., collagen would have been obvious over the collagen ([0041], [0077], [0125], claims 1 and 7), as taught by Ma. The limitation of a pancreatic beta cell would have been obvious over the pancreatic islet cells ([0087], [0147]), and beta cells ([0037]), as taught by Ma.
Regarding instant claim 17, the limitation of the hydrogel comprising collagen would have been obvious over the collagen ([0041], [0077], [0125], claims 1 and 7), as taught by Ma. The limitation of a pancreatic beta cell would have been obvious over the pancreatic islet cells ([0087], [0147]), and beta cells ([0037]), as taught by Ma.
Claims 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (US 2014/0271843 A1 – “Ma”) in view of Lee et al. (International Journal of Biological Macromolecules 110 (2018) 497-503 – “Lee”), as applied to claims 1-9 and 16-17 above, in view of Mooney et al. (US 2008/0044900 A1 – “Mooney”).
Instant claim 18 is drawn to the implant according to claim 17, wherein the microporous scaffold comprises a polysaccharide.
The teachings of Ma and Lee are discussed above.
Ma and Lee do not expressly teach that the microporous scaffold comprises a polysaccharide.
Mooney teaches scaffolds for cell transplantation (Title and Abstract). Polymeric carriers include CMC (carboxymethyl cellulose) and collagen-CMC ([0079]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare multi-layer hydrogel capsules for encapsulation of cells, including pancreatic islet cells and beta cells, wherein biocompatible polymers for encapsulating cells include collagen, as taught by Ma, in view of the use of tannic acid for cross-linking cell-laden collagen, as taught by Lee, and the use of CMC in scaffolds for cell transplantation, as taught by Mooney, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the teachings of Ma, Lee, and Mooney because all the references are drawn to enclosing/encapsulating and delivering cells, and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A). Furthermore, Mooney teaches the advantages of using their scaffold including achieving maximum therapeutic efficacy, and sustained delivery facilitating accretive integration of therapeutic cells into tissue at a desired location ([0099]).
Regarding instant claim 18, the limitation of the microporous scaffold comprising a polysaccharide would have been obvious over the scaffolds for cell transplantation (Title and Abstract) including the polysaccharide CMC and collagen-CMC ([0079]), as taught by Mooney.
Regarding instant claim 20, the limitation of the polysaccharide which is a carboxymethyl cellulose would have been obvious over the CMC ([0079]), as taught by Mooney.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARADHANA SASAN whose telephone number is (571)272-9022. The examiner can normally be reached Monday to Friday from 6:30 am to 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached on 571-272-6023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615