DETAILED CORRESPONDENCE
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 of invention and/or species, and corresponding claims (1-4, 6, 8, 10, 12, 15, 18, 24, 27, 28, 30, 31, 34, 35, and 41) is acknowledged. The election has been made without traverse. Non-elected claims are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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(s) 15 is/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 pre-AIA the applicant regards as the invention.
In reference to claim 15, “Ficoll” is a brand name.
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 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.
Claim 1, 3, 8, 15, 18, 24, 27, 34, 35, 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Christoph (NPL 20151).
In reference to claim 1, Christoph discloses a method of making a frozen, three-dimensional, cell-laden bioink scaffold by additive manufacturing methods or casting, comprising (“encapsulate living cells and shaping cell-containing materials into solid statemacroporous foams with precisely controlled morphology. Our strategy is based on freeze casting” [Abstract]):
i) providing an aqueous solution comprising an effective amount of a first biocompatible polymer (“Prior to the freeze casting process, 200 mL of yeast cells dispersed in PBS (approximately 4 x 107 cells) were added to the alginate sol.” [Section 2.3]. Alginate is the polymer);
ii) adding an effective amount of a cryoprotectant to the aqueous solution; (In the last paragraph of Section 3, Christoph discloses the experiment was performed “in the absence of commonly-used cryoprotecting agent such as DMSO, glycerol, trehalose, sucrose, or ethanol”. Christoph does not demonstrate the addition of cryoprotectant to their solution, but recognizes that it is common to do so, and does not teach away from doing so, and therefore it would be obvious to a person of skill in the art to add a protectant to the solution in order to further protect the cells);
iii) optionally adding an effective amount of an agent to the aqueous solution or subjecting the aqueous solution to a condition that promotes crosslinking of the first biocompatible polymer;
iv) adding cells to the aqueous solution to make a cell-laden bioink aqueous solution; (“Prior to the freeze casting process, 200 mL of yeast cells dispersed in PBS (approximately 4 x 107 cells) were added to the alginate sol.” [Section 2.3]);
v) casting the cell-laden bioink aqueous solution in a three-dimensional mold at a subzero temperature, bioprinting the cell-laden bioink aqueous solution at a subzero temperature, or infusing the cell-laden bioink aqueous solution into a solid scaffold at a subzero temperature to produce a frozen, three-dimensional, cell-laden bioink scaffold (“Prior to the freeze casting process, 200 mL of yeast cells dispersed in PBS (approximately 4 x 107 cells) were added to the alginate sol.” [Section 2.3]).
In reference to claim 3 the cited prior art discloses the invention as in claim 1.
Christoph discloses wherein the first biocompatible polymer comprises an alginate. (“alginate sol at 4 wt%” [Section 2.1])
In reference to claim 8 the cited prior art discloses the invention as in claim 3.
Christoph discloses wherein alginate is present in the cell-laden bioink solution in an amount of from about 0.1% by weight to about 10% by weight (“alginate sol at 4 wt%” [Section 2.1])
In reference to claim 15 the cited prior art discloses the invention as in claim 1.
Christoph discloses wherein the cryoprotectant is selected from DMSO, polyvinylpyrrolidone (PVP), sucrose, glycerol, polyethylene glycol (PEG), ethylene glycol (EG), Ficoll, polyvinyl alcohol, polyglycerol and combinations thereof (“commonly-used cryoprotecting agent such as DMSO,glycerol, trehalose, sucrose, or ethanol” [Last paragraph of Section 3])
In reference to claim 18 the cited prior art discloses the invention as in claim 1.
The agent is optional.
In reference to claim 24 the cited prior art discloses the invention as in claim 1.
Christoph discloses “sample was cooled down to -60 *C” using liquid nitrogen (Section 2.1), not dry ice, however, it is well known to use dry ice to cool items. Therefore it would be obvious to use dry ice instead as an art recognized alternative suitable for the same intended purpose.
In reference to claim 27 the cited prior art discloses the invention as in claim 1.
Christoph discloses “extension of this method toother cell types and different biological hydrocolloids must now be explored to fully evaluate its potential in biotechnology and medicine… The processing flexibility of freeze casting can also provide additional tunable complexity to the three-dimensional environment imposed on cells and contribute to current research on the implications of predefined geometric boundaries on tissue growth.[” (End of Section 4, end of the paper). This implies that tissue cell would be used.
In reference to claim 34 the cited prior art discloses the invention as in claim 1.
Chrisoph discloses wherein the frozen, cell-laden bioink scaffold is capable of being cryopreserved and stored at −80° C. for an extended period of time without significant damage to the scaffold or the cells within the scaffold (the same materials and procesing would have the same properties).
In reference to claim 35 the cited prior art discloses the invention as in claim 1.
Chrisoph discloses thawing the frozen, three-dimensional, cell-laden bioink scaffold, wherein the frozen, three-dimensional, cell-laden bioink scaffold is optionally thawed in the presence of an effective amount of a crosslinker, wherein the three-dimensional, cell-laden bioink scaffold maintains structural integrity after thawing, wherein the three-dimensional, cell-laden bioink scaffold exhibits little or no interlayer mixing during casting or bioprinting and after thawing (“thawing after freezing the monoliths” [Caption to Fig 4]).
In reference to claim 41 the cited prior art discloses the invention as in claim 1.
Chrisoph discloses wherein the thawed, three-dimensional, cell-laden bioink scaffold has a compressive strength of between about 2-3 kPa at 37° C. in submersion conditions, has a yield strength of about 1.5-2.0 kPa, and has a bulk elastic modulus of about 0.05-0.09 kPa, and is capable of supporting cellular proliferation, cellular differentiation, cellular migration, and/or tissue organization (the same materials and procesing would have the same properties).
Claim 2, 4, 6, 10, 28, 30, 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Christoph (NPL 20152) and further in view of Wegst (US 20120149111 A1)
In reference to claim 2 , 31 the cited prior art discloses the invention as in claim 1.
Christoph further discloses the “extension of this method toother cell types and different biological hydrocolloids must now be explored to fully evaluate its potential in biotechnology and medicine… The processing flexibility of freeze casting can also provide additional tunable complexity to the three-dimensional environment imposed on cells and contribute to current research on the implications of predefined geometric boundaries on tissue growth.[” (End of Section 4, end of the paper), but does not describe the different biological hydrocolloids to be explored including the inclusion of a second compatible polymer.
In the same field of endeavor or reasonably pertinent to the particular problem faced by the inventor, scaffolds (title), Wegst discloses a similar method (abstract); wherein “the scaffolds of the present invention can be constructed from a variety of polymer compositions, including, but not limited to, … alginate, … collagen, elastin, …, in any concentration and in any ratio” (P0108).
Christoph indicates that other materials should be used and Wegst provides exemplary materials suitable for the same intended purpose.
Therefore, it would have been obvious to one of ordinary skill in the art with a reasonable expectation of success before the effective filing date of the claimed invention to configure the method by adding to the aqueous solution an effective amount of a second biocompatible polymer, or combining the aqueous solution comprising an effective amount of a first biocompatible polymer with a second aqueous solution comprising an effective amount of a second biocompatible polymer.
In reference to claim 4 the cited prior art discloses the invention as in claim 2.
Wegst discloses wherein the second biocompatible polymer comprises gelatin or collagen (P0108, quoted above).
In reference to claim 6 the cited prior art discloses the invention as in claim 2.
Wegst wherein the weight ratio of the first biocompatible polymer to the second biocompatible polymer is from about 1:10 to about 10:1 (“any ratio” in P0108 overlaps with the claimed range, quoted above; also see “the polymer may be a polyelectrolyte complex mixture (PEC) formed from a 1:1 solution of chitosan and alginate” [P0114]).
In reference to claim 10 the cited prior art discloses the invention as in claim 4.
Wegst further discloses an example wherein gelatin is present in the cell-laden bioink solution in an amount of about 0.1% by weight to about 10% by weight (“polymer solutions can include varying amounts of gelatin in combination with varying amounts of chitosan, each dissolved in an acidic solution. The concentration of the acid can be adjusted depending on the amount of gelatin in combination with chitosan that is dissolved. In one aspect, the acidic solution is 1% (v/v) acetic acid. In one embodiment, the amount of gelatin in solution is between about 1-10% (w/v) and any whole or partial increments therebetween.” [P0102]).
In reference to claim 28, 30 the cited prior art discloses the invention as in claim 4.
Christoph further discloses bioactives, but not as intended by applicant when read in light of the specification. Wegst further discloses wherein the cell-laden bioink solution further comprises one or more bioactive molecules; wherein the bioactive molecule is selected from a growth factor, cytokine, hormone, drug, immunosuppressant, antibiotic, biologic, antibody, chemotherapeutic agent, and combinations thereof. (“locate the bioactive microcapsules, the freeze casting is performed in stages, adding polymer/bioactive mixtures at points where the bioactive agent is required, for example enzyme” [P0182]) in order to form a gradient material having specialized properties (P0182).
Claim 2, 4, 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Christoph (NPL 20153) and further in view of Wegst2 (US 20180153734 A1)
In reference to claim 2, 4, 12 the cited prior art discloses the invention as in claim 6.
Christoph further discloses the “extension of this method toother cell types and different biological hydrocolloids must now be explored to fully evaluate its potential in biotechnology and medicine… The processing flexibility of freeze casting can also provide additional tunable complexity to the three-dimensional environment imposed on cells and contribute to current research on the implications of predefined geometric boundaries on tissue growth.[” (End of Section 4, end of the paper), but does not describe the different biological hydrocolloids to be explored including the inclusion of a second compatible polymer.
In the same field of endeavor or reasonably pertinent to the particular problem faced by the inventor, scaffolds (title), Wegst discloses a similar method (abstract); wherein the scaffolds are formed from “Collagen-Nanocellulose (50:50)" (P0035) by combining “mass equal amounts of the 1% slurries (collagen and nanocellulose)” (P0043) and explains that these are useful for certain applications.
Christoph indicates that other materials should be used and Wegst2 provides exemplary materials suitable for the same intended purpose.
Therefore, it would have been obvious to one of ordinary skill in the art with a reasonable expectation of success before the effective filing date of the claimed invention to configure the method by adding to the aqueous solution an effective amount of a second biocompatible polymer, or combining the aqueous solution comprising an effective amount of a first biocompatible polymer with a second aqueous solution comprising an effective amount of a second biocompatible polymer; wherein the weight ratio of the first biocompatible polymer to the second biocompatible polymer is from about 1:10 to about 10:1; and collagen is present in the cell-laden bioink solution in an amount of about 0.15% by weight to about 10% by weight.
Conclusion
Any prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICHOLAS KRASNOW whose telephone number is (571)270-1154. The examiner can normally be reached M-R: 8am-5pm.
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/NICHOLAS KRASNOW/Examiner, Art Unit 1744
1 https://onlinelibrary.wiley.com/doi/epdf/10.1002/mabi.201500319
2 https://onlinelibrary.wiley.com/doi/epdf/10.1002/mabi.201500319
3 https://onlinelibrary.wiley.com/doi/epdf/10.1002/mabi.201500319
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