DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 27 April 2026. Claim 1 has been amended. Claims 12-17 remain withdrawn. Claims 1, 5-9, 11, 18, and 19 are currently pending and under examination.
This application is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2021/019933, filed February 26, 2021, which claims benefit of priority to U.S. Provisional Application No. 62/082449, filed February 27, 2020.
Maintained/Modified Rejections Necessitated by Amendment:
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 1, 5-9, 11, 18, and 19 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.
Claim 1 as amended recites in relevant part “wherein heparin and heparin-bound basic Fibroblast Growth Factor exhibit a preferred patterning on said TiB2 exposed portions.” This claim is indefinite, because as currently written, it is unclear if the heparin and heparin-bound basic Fibroblast Growth Factor indicated as exhibiting preferred patterning on the TiB2 exposed portions are intended to be the heparin and heparin-bound basic Fibroblast Growth Factor previously recited in the claim (i.e. the heparin and heparin-bound bFGF on the surface exhibit this), or instead, if this is intended to simply indicate a functional property of heparin and heparin-bound bFGF, but not intended to limit the structure of the composition (i.e. heparin and heparin-bound bFGF in general exhibit this property).
Claims 5-9, 11, 18, and 19 are included in this rejection as these claims depend from above rejected claim 1, and fail to remedy the noted deficiency.
Response to Arguments
Applicant urges that the amendments overcome the indefiniteness rejection. Applicant’s arguments have been fully considered, but have not been found persuasive. The newly added limitation is indefinite for the reasons discussed above.
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.
Claims 1, 5-9, 11, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Das (IDS; Microfabrication of Titanium Diboride Patterned on Silicon Substrates for Mono- And Coculture of Endothelial and Mesenchymal Stem Cells, May 2014, Dissertation), in view of Industry Academic Cooperation Foundation of Chung Ang University (WO 2017/159943A1, published 2017-09-21, hereafter Chung Ang University; English translation provided by Examiner and referenced hereafter – Previously Presented).
With regard to claims 1, 11, and 18, Das teaches a composition comprising a patterned surface comprising a silicon-containing substrate, including Si or SiO2/Si, and diboride in the form of TiB2, patterned on the silicon substrate, where the patterned surface comprises both silicon and diboride exposed portions (Abs.; p. 95, Para. 2; Fig. 6.1(e)). MSCs and HUVECs are cultured using the composition (p. 71, 4.6.3).
While it is further taught that heparin is included with growth factors for culture of cells on the substrate of the composition (p. 68, 4.5.1, para. 1 to p. 69, para. 2), it is not taught that the composition further comprises heparin-bound basic fibroblast growth factor (bFGF).
Chung Ang University teach a well-plate for culture of cells, including MSCs, the well-plate including culture medium comprising heparin and a fibroblast growth factor (bFGF)-heparin complex, which is heparin-bound bFGF, the complex providing the growth factor with improved structural stability and cell proliferation effect (Abs.; p. 2, para. 4-5; p. 3, Example 8).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Das and Chung Ang University, because both teach a cell culture substrate for culturing cells, including MSCs, and culture media comprising heparin and growth factors. The inclusion of heparin-bound bFGF on a cell culture substrate is known in the art as taught by Chung Ang University. An ordinary artisan would have been motivated to further include heparin-bound bFGF in the composition of Das, because the complex provides the growth factor with improved structural stability and cell proliferation effect, including for MSCs. As such, the inclusion of bFGF as an additional growth factor bound to heparin would have been expected to predictably improve the composition of Das.
It is noted that the meaning of the limitation that “heparin and heparin-bound bFGF exhibit a preferred patterning” is unclear as discussed in the indefiniteness rejection above. This limitation does not provide a structural limitation that further limits the composition as claimed, it instead recites an inherent function of heparin and heparin-bound bFGF when exposed to diboride patterned on a silicon substrate. Heparin and heparin-bound bFGF cannot be separated from their properties and functions. Absent any necessary but unrecited features in the claim, the heparin and heparin-bound bFGF in the composition as rendered obvious by Das and Chung Ang University would necessarily exhibit the inherent property of exhibiting a preferred patterning on the TiB2 exposed portions.
With regard to claims 5-7 and 19, Das teaches that the patterned surface comprises one or more TiB2 exposed zones surrounded by exposed silicon regions; the TiB2 zones in the form of geometric shapes including lines, circles, squares, rectangles, and ovals; (see Figs. 6.1(e), 6.7). The square zone having a length/width of 200 µm (see Fig. 6.1(e)), and circles having a diameter of 100 µm to 500 µm (p. 123, 6.1.1.2, line 1-3), which are fully encompassed within 50 to 1000 µm. The diboride exposed zones including, for example, 25 circles (see Fig. 4.2(c)-(d)).
With regard to claims 8 and 9, taken together, Das and Chung Ang University render obvious the composition as claimed, including the components as claimed. As the composition cannot be separated from its properties, the patterned surface is necessarily capable of enabling a 3D microenvironment via cell aggregation; and is necessarily capable of being located in a microwell, on a slide, chip or wafer, or tissue culture flasks.
Response to Arguments
Applicant urges that neither reference teaches or suggests the amended limitation. Additionally, Chung Ang University has nothing to do with patterning, and thus an ordinary artisan would not combine the cited references absent hindsight reasoning. Further, the currently claimed heparin-bound bFGF is not the same as the chemically bound bFGF-heparin complex of Chung Ang University.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that neither reference teaches or suggest the amended limitation; as discussed in the modified rejection above, the meaning of the limitation that “heparin and heparin-bound bFGF exhibit a preferred patterning” is unclear. This limitation does not provide a structural limitation that further limits the composition as claimed, it instead recites an inherent function of heparin and heparin-bound bFGF when exposed to diboride patterned on a silicon substrate. Heparin and heparin-bound bFGF cannot be separated from their properties and functions. Absent any necessary but unrecited features in the claim, the heparin and heparin-bound bFGF in the composition as rendered obvious by Das and Chung Ang University would necessarily exhibit the inherent property of exhibiting a preferred patterning on the TiB2 exposed portions. It appears that Applicant may be intending to limit the structure of the composition such that the heparin and heparin-bound bFGF are present on the TiB2 exposed portions at a higher concentration than on the silicon substrate portions.
With regard to Applicant’s argument that Chung Ang University has nothing to do with patterning, and thus an ordinary artisan would not combine the cited references absent hindsight reasoning; in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Here, the motivation to combine Das with Chung Ang University is not based on a desire to provide preferred patterning. Instead, it would have been obvious to one of ordinary skill in the art to combine the teachings of Das and Chung Ang University, because both teach a cell culture substrate for culturing cells, including MSCs, and culture media comprising heparin and growth factors. An ordinary artisan would have been motivated to further include heparin-bound bFGF as taught by Chung Ang University in the composition of Das, because the complex provides the growth factor with improved structural stability and cell proliferation effect, including for MSCs.
With regard to Applicant’s argument that the currently claimed heparin-bound bFGF is not the same as the chemically bound bFGF-heparin complex of Chung Ang University; it is noted that Applicant has not narrowly defined the term “heparin-bound basic Fibroblast Growth Factor.” As such, the bFGF-heparin complex of Chung Ang University reads on the limitation as currently claimed.
Conclusion
No claims are allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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