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
Claims 1-3, 5, 7, 12 and 14-21 as amended and new claims 36-39 on 12/01/2025 are currently pending and under examination in the instant office action.
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 1-3, 5, 7, 12 and 14-21 as amended and new claims 36-39 remain/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/049066 (Keselowsky et al) and Reakasame et al. (“Oxidized alginate-based hydrogels for tissue engineering applications: a review”. Biomacromolecules 2018, Vol. 19, issue 1, pages 3-21; published November 27, 2017).
The cited reference WO 2017/049066 (Keselowsky et al) teaches a method for forming 3D tissue constructs by depositing an ink/bioink material comprising cells into a hydrogel support material (0027, 0040), wherein the hydrogel material undergoes a temporary phase change due to applied force, become fluid and then solid again when applied stress is removed (0044, 0066), thus, avoiding a negative compressive force on the cells that results from growth of the cells unlike the use of traditional inflexible support medium structures (0034); wherein the hydrogel material comprises pluralities of particles having size in the ranges 0.1 µm to 100 µm (par. 0042, 0076); wherein the hydrogel support is capable to maintain a shape of the delivered bioink material (0044); wherein the method allows for the deposited (or the printed bioink) cells to form a defined/desired shape (par. 0053-0054, 0044) and to be removed from the scaffold of support medium.
Thus, as applied to the claimed method (claims 1-3 as amended and new claims 36 and 39), the cited WO 2017/049066 (Keselowsky et al) teaches a method for forming 3D tissue constructs, wherein the method comprises:
Step of providing a hydrogel support medium, wherein the hydrogel material is granular and/or comprises pluralities of particles (0027), wherein the hydrogel particles are made from polymer materials (0060, 0066), wherein the hydrogel support material is self-healing (par. 0066, line 6), cross-linkable or partially crosslinked (0068), the gel material is shear thinning (0072) and undergoes a temporary phase change due to applied force (0044, 0066), thus, avoiding a negative compressive force on the cells that results from growth of the cells unlike the use of traditional inflexible support medium structures (0034) within the meaning of claim 1 as amended and new claims 36 and 39;
Step of depositing the cells into the hydrogel support medium (par. 0027, 0046) or “printing” a first bioink into the hydrogel support medium, wherein the bioink includes a plurality of cells, wherein the cells are deposited to form a desired 3D shape (0053-0054) and the printed/deposited cells maintain their shape or printed geometry (0054); wherein the plurality of cells are printed either with or without supplemental matrix materials (par. 0069, lines 6-8), thus, either optionally comprising macromers or free of macromeres within the meaning of claim 1 as amended and new claims 36 and 39;
Step of crosslinking (or reversible crosslinking) the polymer macromers of hydrogel support medium printed with the first bioink within the meaning of the claims since the gel material is shear thinning (0072) which undergoes a temporary phase change (from solid to fluid and back to solid) as result of applied force and removal of force (0044, 0066) including loading cells upon printing and resting afterwards within the broadest meaning of claim 1 as amended, claim 3 and new claims 36 and 39;
and
Step of culturing the printed plurality of cells (0027, 0038-0039) in the hydrogel support medium to form cell aggregates or tissue construct with the defined shape (0038-0039) within the broadest meaning of claim 1 as amended, claim 2 and new claims 36 and 39;
The cited method further comprises step of removal of cells (0031-0032) or retrieving cells (0047), thereby, separating the printed/deposited construct, thus, forming a scaffold free 3D tissue within meaning of the claim 5.
Thus, the cited method of WO 2017/049066 (Keselowsky et al) is sustainably similar, if not the same, as claimed, wherein in the cited method a hydrogel support medium is made from synthetic polymers such as acrylic Carbonyl and/or silicone PDMS (0060, 0066).
But the cited WO 2017/049066 (Keselowsky et al) is silent about the use a natural polymer (as recited in claims 1, 36 and 39) including of oxidized, acrylated and/or methacrylated alginates as hydrogel material for cell support (claims 37 and 38).
However, it is well known that natural polymer-based hydrogels are ideal scaffolds for tissues engineering for their biocompatibility and biodegradability as clearly acknowledged by the cited reference by Reakasame (see introduction on page 3, col.1, par. 3). In particular, the cited reference by Reakasame teaches the use of oxidized methacrylated alginates (OMA) as hydrogel material for cell support (page 8, col. 1).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to use natural polymer for hydrogel support medium including oxidized methacrylated alginates (OMA) as polymeric materials for providing hydrogel support medium granules in the method for printing/forming 3D tissue constructs of the cited WO 2017/049066 (Keselowsky et al) with a reasonable expectation of success in culturing cells printed into polymeric support medium and forming scaffold free 3D tissue structure because it is well known and recognized that natural polymer-based hydrogels including OMA are ideal scaffolds for tissues engineering for their biocompatibility and biodegradability as clearly acknowledged by the cited reference by Reakasame.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
As applied to claims 4 and 12: in the methods of the cited references polymeric hydrogel support materials are/can be photo-crosslinked; for example: see Reakasame at page 8, col. 1. For example: see WO 2017/049066 (Keselowsky et al) at par. 0073, 00113.
As applied to claim 7: in the cited method of WO 2017/049066 (Keselowsky et al) the hydrogel material comprises pluralities of particles having size in the ranges 0.1 µm to 100 µm (par. 0042, 0076) which overlaps the claimed range.
As applied to claim 14: it is well known and recognized that natural polymer-based hydrogels including OMA are ideal scaffolds for tissues engineering for their biocompatibility and biodegradability as clearly acknowledged by the cited reference by Reakasame (see pages 1 and 8).
As applied to claims 15-16: in the methods of the cited references the cells are of various types including differentiated cells, cancer tumor cells (see par. 0131, par. 0038-0039 of WO 2017/049066 (Keselowsky et) and mesenchymal stem cells (see page 8, col.1 of Reakasame).
As applied to claim 18: the bioink with cells is provided by injection of cells suspended in a liquid or as a slurry; for example: see par. 0046 of WO 2017/049066 (Keselowsky et).
As applied to claims 19-20: the hydrogel support and the printed bioink with cells are in a cell culture growth medium including cell culture medium as intended for differentiation; for example: see par. 0027, 0038, 0057-0059, 0111 of WO 2017/049066 (Keselowsky et).
As applied to claim 21: different materials including pharmaceuticals and/or bioactive agents may be deposited as second bioink at different locations of hydrogel support medium in addition to the first bioink with cells of interest; for example: see par. 0063, 0079, 00101, 00131 of the cited WO 2017/049066 (Keselowsky et).
Thus, the claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1-3, 5, 7, 12 and 14-21 as amended and new claims 36-39 remain/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/049066 (Keselowsky et al) and Reakasame et al. (“Oxidized alginate-based hydrogels for tissue engineering applications: a review”. Biomacromolecules 2018, Vol. 19, issue 1, pages 3-21; published November 27, 2017) as applied to claims 1-3, 5, 7, 12 and 14-21 as amended and new claims 36-39 above, and further in view Sriamornsak et al (European Journal of Pharmaceutics and Biopharmaceutics, 2007, 67, pages 227-235).
The cited WO 2017/049066 (Keselowsky et al) and Reakasame et al are relied upon as explained above.
The cited reference WO 2017/049066 (Keselowsky et al) teaches a method for forming 3D tissue constructs by depositing an ink/bioink material comprising cells into a hydrogel material (0027, 0040), wherein the hydrogel material is synthetic and comprises pluralities of particles having size in the ranges 0.1 µm to 100 µm (par. 0042, 0076.
However, it is well known that natural polymer-based hydrogels including oxidized methacrylated alginates (OMA), that are taught by Reakasame, are ideal scaffolds for tissues engineering for their biocompatibility and biodegradability as clearly acknowledged by the cited reference by Reakasame (see page 3 and 8).
Further, the reference by Sriamornsak teaches that alginate-based hydrogel particles can be made to provide for the same particle diameters in the range 100 µm (see table 1) and higher (figure 1) as the synthetic polymers of WO 2017/049066 (Keselowsky et al) and as encompassed by the claim 7.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed on 12/01/2025 have been fully considered but they are not all found persuasive.
With regard to claim rejections under 35 USC § 103 Applicants’ main argument appears to be that the method of the cited WO 2017/049066 (Keselowsky et al) does not comprise or does not encompass step of “crosslinking” hydrogel polymer macromeres after printing cells thereon (paragraph bridging pages 12 and 13 of the last response).
This argument is not found persuasives because the cited WO 2017/049066 (Keselowsky et al) explicitly teaches that the granular hydrogel support material is self-healing (par. 0066, line 6), cross-linkable (0068), the gel material is shear-thinning and characterized by viscosity reduction under stress and return to solid like-state when stress is removed (0072), it undergoes a temporary phase change due to applied force (0044, 0066). Thus, the cited hydrogel is characterized by a reversible cross-linking when it undergoes a phase change when force/stress is applied during depositing cell suspensions thereon and it returns to solid like state at rest when cells are printed thereon. Therefore, the use of hydrogel which undergoes a phase change in the cited method encompass the step of crosslinking polymer macromers to each other in the hydrogel support medium within the broadest reasonable meaning of the claims.
Further, with regard to the disclosure by Reakasame Applicants argue that there is nothing in Reakasame that would lead one of skill in the art to use OMA as yield stress material of Keselowsky (response page 13, par. 2). This argument is not found persuasive because the cross-linking of oxidized alginates-based hydrogel of Reakasame is generally regarded as self-healing and reversible as evidenced by Hafeez (abstract). Thus, it would be considered as substitution of functional equivalents.
No claims are allowed.
Conclusion
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 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.
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Vera Afremova
May 1, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653
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