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 .
DETAILED ACTION
Claims 1, 2, 4, 6, 7, 9-11, 13, 15-19, 27-32 are pending in the Claim Set filed 3/2/2026.
Applicants’ election of Group I: claims 1-4, 6, 7 and 9-11 in the reply filed on 8/27/2035 is acknowledged. Applicants elected species: cardiomyocytes and endothelial cells. Herein, the cells type has been extended to include smooth muscle cells.
Claims 13 and 15-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 27-32 are newly added.
Claims 3, 5, 8,12, 14 and 20-24 are cancelled. Also, included are cancelled claims 25 and 26 (See below ‘Regarding Instant Claims’).
Herein, claims 1, 2, 4, 6, 7, 9-11 and 27-32 are for examination to the extent that they read on the elected/extended species.
Regarding Instant Claims
Claims 20-24 have been cancelled. However, the subsequent claim is numbered as claim 27. Thus, it appears that Applicant misnumbered the cancelled claims. Herein, in the interest of compact prosecution, claims 20-24 and claims 25-26 are interpreted as cancelled.
Withdrawn Rejections
The rejection of claims 1-4, 6, 7 and 9-11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the claim amendments.
The rejection of claims 2 and 6 and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the claim amendments.
The rejection of claims 1, 2, 6, 7 and 9-11 under 35 U.S.C. 103 as being unpatentable over of Chan et al (US 20090248145) is withdrawn in view of the claim amendments.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.
The rejection of claims 7, 9, and 10 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 is maintained.
Claims 7, 9, and 10 lack antecedent basis.
Claim 7 recites: The method of claim 1, wherein cells are aligned in a uniform direction in at least a portion of at least one sheet of cells.
‘at least one sheet of cells’ creates an antecedent issue for the sheet since claim 1 can be interpreted as requiring separate sheets, thus it is unclear if a portion of at least one sheet of cells refers back to the at least one sheet of claim 1.
Claim 9 recites: The method of claim 1, wherein the cells comprise a muscle cell.
Claim 1 recites ‘at least one sheet or layer of cells (i.e. at least one layer of cells). Claim 9 recites “the cells” creating an antecedent basis issue.
Claim 10 recites: The method of claim 1, wherein the cells comprise smooth muscle cells, cardiac cells, skeletal cells, neuronal cells, cancer cells, endothelial cells, epithelial cells, fibroblasts, chondrocytes, and combinations thereof.
Claim 1 recites ‘at least one sheet or layer of cells (i.e. at least one layer of cells). Claim 10 recites “the cells” creating an antecedent basis issue as two recitations of cells are recited in claim 1.
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, 2, 4, 6, 7, 9-11 and 27-32 are rejected under 35 U.S.C. 103 as being unpatentable over of Chan et al (US 20090248145) [Chan] in view of Mizutani et al (US2011/0229962) [Mizutani]. Rejection has been reformulated necessitated by claim amendments.
Regarding claims 1, 2, 4, 6, 7, 9-11, 27-32,
Chan teaches a method of forming a three-dimensional structure of unidirectionally aligned cells, wherein a second plurality of cells are seeded (layered) onto a first plurality of cells, (i.e., a single layer of cells), wherein the cells are aligned unidirectionally to form layers of aligned cells, wherein the cells are endothelial comprising smooth muscle cells, wherein the aligned cells are formed in a pattern onto a scaffold that is flexible to any extent, wherein the scaffold may be of any geometry [Abstract; (0041; 0045; 0050-0051; 0059; 0061; 0088, 0092); Figs,13-21: [0026-035]; see entire document). Furthermore, Chan teaches that the scaffold is wrapped into a tubular form [0110], i.e., flexible scaffold is capable of being wrapped, wherein cell-cell interaction between wrapping layers provides hydrogel microchannel scaffold ([0110; claim 9). The smooth muscle cells can be monolayer, see paragraphs ([0104]; [0107]; claim 17). Further, Cham teaches that scaffold is formed comprising a UV (ultraviolent- curable polymer), e.g., poly(ε-caprolactone-r-L-lactide-r-glycolide) (PCLLGA) diacrylate (PCLLGA diacrylate) ([0073], Figure 5; [0091-0097]; [0109]); see entire document).
Chan differs from the claims in that the documents do not teach that the flexible scaffold comprises a thermoresponsive material (poly(N-isopropylacrylamide), wherein the flexible scaffold detaches at about 32°C, and at greater than about 32°C the flexible scaffold attaches.
However, Mizutani cures the deficiencies.
Mizutani teaches a temperature-responsive cell culture substrate (scaffold) having a surface that allows cells to adhere thereto and to grow thereon during cell culturing and that allows the adhering and grown cells to be detached therefrom by changing the culturing temperature and a surface. (Abstract; [0008-0014]; see entire document). Furthermore, Mizutani teaches that the thermoresponsive polymer is poly(N-isopropylacrylamide), wherein poly(N-iso propylacrylamide) is known as a polymer having a lower critical solution temperature of 310C and causes dehydration in water at a temperature of 310C. or higher if it is a free state to aggregate the polymer chains to cause white turbidity; whereas, at a temperature of lower than 310C, the polymer chains are hydrated into a water-dissolved state. Mizutani teaches that this polymer is fixed to the surface that allows cells to adhere thereto and to grow thereon during cell culturing and that allows the adhering and grown cells to be detached therefrom by changing the culturing temperature, the polymer on the substrate surface is similarly dehydrated at a temperature of 310C, or higher (i.e., about 320C), and since the polymer chain covers the substrate surface and is fixed thereto, the substrate surface shows hydrophobicity. Conversely, at a temperature lower than about 310C, the polymer on the substrate surface is hydrated, while the polymer chain covers the substrate surface and is fixed thereto; thus, the substrate surface shows hydrophilicity. The hydrophobic surface is a surface suitable for adhesion and growth of cells, while the hydrophilic surface is a surface to which cells cannot adhere. Accordingly, cells during culturing can be detached by merely cooling. Meanwhile, in the surface that does not allow cells to adhere thereto at all, since the grafted density of poly(N-isopropylacrylamide) is too high, cells do not adhere thereto at all. That is, cells adhere to and to grow in a predetermined region only, and the cells can be detached by changing the culturing temperature ([0037]; claims 1-5).
Thus, it would have been obvious to one of ordinary skill in the art to modify Chan to provide a flexible scaffold comprising a thermoresponsive polymer that is poly(N-isopropylacrylamide). One skilled in the art would have been motivated to provide a flexible scaffold comprising a three-dimensional structure of unidirectionally aligned cells as taught by Chan that is a flexible scaffold comprising poly(N-isopropylacrylamide) whereby cells, e.g., muscle cells, can be detached from the scaffold merely by changing the temperature (see Mizutani [0015]; [0037]). One skilled in the art would have recognized that this would allow removal of the cells, muscle cells, from the scaffold by simply changing the temperature and thereby prevent damage to the cells that could occur from mechanical separation methods. Notably, Chan teaches, in an embodiment, the scaffold used in the method may be degraded to any desired extent during or after the method of the invention, as long as a three-dimensional structure of unidirectionally aligned cells has already been formed and the cells are allowed to remain essentially intact. Furthermore, Chan teaches that scaffold comprises PCLLGA diacrylate (i.e., an UV curable polymer, of which is distinctly different from poly(N-isopropylacrylamide). Further, Chan teaches the cell-cell interaction between wrapping layers provide a hydrogel microchannel scaffold
Thus, when using the method of the invention it may be possible to avoid problems arising from the scaffold such as contamination or integration of the scaffold into recipient tissue [Chan paragraph [0061]. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (In re Kahn, 78 USPQ2d 1329, 1336, Federal Circuit 2006). See MPEP § 2144, IV.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to provide instantly claimed tissue engineering scaffold and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the claimed invention as a whole would have been obvious to one of ordinary skill as evidenced by Chan and Mizautani, as a whole.
Response to Arguments
Applicants argue that Mizutani is clearly distinct and would not have been considered by the skilled worker. Applicants argue that nowhere does Mizutani or any of the other cited documents suggest that the cited material of Mizutani could be utilized in the steps recited in Applicant's clams, or create a tissue engineering scaffold as recited in those claims.
Applicants argue that the instant rejection is the result from improper hindsight reconstruction of Applicant's claimed subject matter.
Applicant’s arguments have been fully considered but they are not persuasive, because the scaffold as taught by Chan and Mizautani, as a whole, provides for cell attachment and tissue growth and attachment of targeting molecules. Moreover, it would have been obvious to one of ordinary skill in the art to modify Chan to provide a flexible scaffold comprising a thermoresponsive polymer that is poly(N-isopropyl acrylamide) as taught by Mizautani. One skilled in the art would have been motivated to provide a flexible scaffold comprising a three-dimensional structure of unidirectionally aligned cells as taught by Chan that is a flexible scaffold comprising poly(N-isopropylacrylamide) whereby cells, e.g., muscle cells, can be detached from the scaffold merely by changing the temperature (see Mizutani [0015]; [0037]). One skilled in the art would have recognized that this would allow removal of the cells, muscle cells, from the scaffold by simply changing the temperature and thereby prevent damage to the cells that could occur from mechanical separation methods. Furthermore, Chan teaches that scaffold comprises PCLLGA diacrylate (i.e., an UV curable polymer), of which is distinctly different from poly(N-isopropylacrylamide). Chan teaches the cell-cell interaction between wrapping layers provide a hydrogel microchannel scaffold. Chan teaches that scaffold comprises PCLLGA diacrylate is biodegradable. Thus, one of ordinary skill in the art would have had been motivated to provide a scaffold comprising a UV-curable polymer: PCLLGA diacrylate, having a reasonable expectation of success of providing a scaffold comprising improved physical structure that maintains structural integrity, especially in vivo, thus providing a platform for cell growth thereon wherein the presence of poly(N-isopropylacrylamide) would necessarily facilitate the detachment of the cells from the scaffold, thus, retaining membrane integrity and preserving cellular functionality, etc., without relying on enzymes.
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Applicant is reminded that obviousness does not require absolute predictability In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). In the instant case, Applicants have failed to provide evidence showing there was no reasonable expectation of success.
Regarding allegations of hindsight, Applicants argue that the examiner's conclusion of obviousness is based on improper hindsight provided by the present disclosure. However, any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from appellant's disclosure, such a reconstruction is proper. In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). Further, the teachings of Chan et al (US 20090248145) and Mizutani et al (US2011/0229962) were known and available to one of ordinary skill in the art before the effective filing date of the claimed invention and to combine these references to provide an improved scaffold, as described above, is well within the purview of an ordinary artisan.
Conclusions
No claim is 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Thurman Wheeler whose telephone number is (571)-270-1307. The examiner can normally be reached Monday-Friday 11:00am-5:00pm EST.
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/T.W./ Examiner, Art Unit 1619
/SARAH ALAWADI/Primary Examiner, Art Unit 1619
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