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
This action is in response to the papers filed February 22, 2024.
Claim Amendments
Applicant’s amendment to the claims filed 02/22/2024 is acknowledged.
Claims 1-15 have been cancelled.
Claims 16-26 are newly added.
Claims 16-26 are pending and under examination.
Priority
The instant application 18/235,476 was filed on 08/18/2023. This application is a continuation (CON) of U.S. Application No. 16/617,753 filed on 11/27/2019, which is a national stage of international application PCT/US2018/034928 filed on 05/29/2018, and claims priority based on U.S. Provisional Application No. 62/512,337 filed on 05/30/2017
Effective filing dates:
The provisional application 62/512,337 does not describe the limitations of a human iPS-derived neural stem cell, a human iPS-derived microglia or a human iPS-derived pericyte, as claimed in claims 20-21, and 25. Therefore, claims 20-21, and 25 do not benefit from the earlier filing date of the provisional application. If applicant believes sufficient written support for the above limitations is found in the provisional application, applicant may respond by specifically identifying where written support is believed to be found in the provisional application.
Information Disclosure Statement
The information disclosure statement (IDS) filed 01/27/2026 does not comply with the requirements of 37 CFR 1.98(d) because the earlier application, U.S. Application No 16/617,753, is not properly identified in the IDS for the copies of references cited and marked with a double asterisk (**). Although it would be proper to reject consideration of the IDS for noncompliance with 37 CFR 1.98(d), the examiner has identified that paper copies of the references cited and marked with a double asterisk (**) are found in U.S. Application No 16/617,753, and the examiner has annotated the signed copy of the IDS accordingly. Therefore, the IDS submitted on 01/27/2026 has been considered. Applicant is respectfully reminded to follow thse requirements of 37 CFR 1.98(d) when relying on an earlier application (as defined under 35 U.S.C. 120) for paper copies of cited references.
Claim Objections
Claims 16-18, 20-25 are objected to because of the following informalities:
In claims 16 and 22, the term “asparate” should be “aspartate” instead.
In claims 16-18, 22-24, the term “norborene” should be “norbornene” instead.
Claims 20-21, and 25 each recite “human vascular endothelial cells (HUVEC),” but the acronym “HUVEC” stands for “Human Umbilical Vein Endothelial Cell,” as recited earlier in the claim. Accordingly, the acronym “HUVEC” should follow the phrase “human umbilical vein endothelial cell” instead.
Appropriate action is required. Applicant should carefully review the claims for typographical errors.
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 16-18, 22-24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Shih et al. (2013) “Visible‐light‐mediated thiol‐Ene hydrogelation using eosin‐Y as the only photoinitiator” Macromolecular rapid communications, 34(3), 269-273; in view of Lim et al. (2016) “New visible-light photoinitiating system for improved print fidelity in gelatin-based bioinks” ACS biomaterials science & engineering, 2(10), 1752-1762; and Zeiger et al. (2013) “Why the dish makes a difference: quantitative comparison of polystyrene culture surfaces” Acta biomaterialia, 9(7), 7354-7361.
Shih discloses a method of generating a visible light photopolymerized hydrogel for cell encapsulation, comprising:
providing a composition, comprising:
eosin-Y, as the photoinitiator;
dithiothreitol (DTT),as the di-thiol-terminated cross-linker; and
CRGDS peptide, as the at least one cysteine-terminated arginine-glycine-aspartate (RGD) peptide;
providing poly(ethylene glycol)-tetra-norbornene (PEG4NB) or poly(ethylene glycol)-tetra-amide-norbornene (PEG4aNB), as the multi-armed poly(ethylene glycol) norbornene; and
photopolymerizing said multi-armed poly(ethylene glycol) norbornene with visible light in the presence of said composition to form said visible light photopolymerized hydrogel.
See, e.g., Abstract; first paragraph on pg. 270; sections 2.2.1 and 2.2.4 on pg. 270.
Shih does not disclose the composition further comprises “tris(bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2),” as claimed in claim 16.
Lim is relevant prior art for teaching methods of generating a photopolymerized hydrogels for cell encapsulation. Lim teaches that conventional systems using ultraviolet (UV) light, e.g., the photoinitiator Irgacure 2959 (I2959), have been shown to influence chromosomal and genetic instability in cells, and UV light has limited penetration depth which may affect the overall polymerization efficiency for large constructs. Therefore, other photoinitiators that absorb visible (Vis) light range, e.g., the photoinitiator ruthenium (Ru) and coinitiator sodium persulfate (SPS), may offer significant advantages for tissue engineering applications. In this study, Lim found that the Vis + Ru/SPS system yielded better cell cytocompatibility compared to the conventional UV + I2959 system. See, e.g., Abstract; and pg. 1753. In the experimental section, use of tris(2,2-bipyridyl)dichlororuthenium(II) hexahydrate is disclosed (see, section 2.1 on pg. 1753), which is found to read on the instantly claimed “tris(bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2)” (claim 16).
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modifying the method of Shih, which used the photoinitiator eosin-Y, by using photoinitiator [Ru(bpy)3]Cl2 and coinitiator SPS instead, as taught by Lim, with a reasonable expectation of success because both systems are suitable for generating hydrogels for cell encapsulation through photopolymerization using visible (Vis), which possess particular advantages over conventional systems using UV light, and Lim found that the Vis + Ru/SPS system yielded better cell cytocompatibility compared to the conventional UV + I2959 system in cell encapsulation experiments.
Shih and Lim do not teach the method further comprises providing a “tissue culture treated polystyrene surface,” as claimed in claim 16.
Zeiger is relevant prior art for teaching tissue culture polystyrene (TCPS) is one of the most commonly used surfaces in mammalian cell biology. After molding, polystyrene vessels (e.g., flasks, dishes, multi-well plates, etc.) are placed in a vacuum chamber and undergo reactive gas plasma and secondary treatments to render the surfaces hydrophilic, enhancing cell-substrate adhesion. See page
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Shih and Lim combined, as set forth above, by further providing a tissue culture treated polystyrene (TCPS) surface, as found in Zeiger, with a reasonable expectation of success because TCPS is one of the most commonly used surfaces in mammalian cell biology, wherein treatment render the polystyrene surface hydrophilic, enhancing cell-substrate adhesion.
For these reasons, claim 16 would have been prima facie obvious over the prior art.
Claim 22 further recites steps of providing one or more cells, and encapsulating said one or more cells in the photopolymerized hydrogel. These steps are taught by Shih (see, e.g., section 2.2.4 on pg. 270) and Lim (see, e.g., sections 2.7 and 2.8 on pg. 1754-1755).
Regarding dependent claims 17 and 23, the combined references provide a photopolymerized hydrogel on a tissue culture treated polystyrene surface formed by a di-thiol-terminated cross-linker and a multi-armed poly(ethylene glycol) norbornene monomer unit, as set forth above, and, therefore, the combined references provide a tissue culture treated polystyrene surface comprises a thiolated substrate and a norbornene-functionalized poly(ethylene glycol) polymer chain, as claimed.
Regarding dependent claims 18 and 24, the chemical structure of polystyrene contains phenol groups, and Shih teaches the monomer unit is a multi-armed poly(ethylene glycol) norbornene, as set forth above. Therefore, the combined references provide a polystyrene surface comprises a phenol-containing substrate and a norbornene-functionalized poly(ethylene glycol) polymer chain, as claimed.
Regarding dependent claim 26, encapsulation of the one or more cells in a 3-dimensional hydrogel is taught by Shih (see, e.g., section 2.2.4 on pg. 270) and Lim (see, e.g., sections 2.7 and 2.8 on pg. 1754-1755).
For these reasons, claims 17-18, 22-24, and 26 would also have been prima facie obvious over the prior art.
Claims 19-21, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Shih et al. (2013) “Visible‐light‐mediated thiol‐Ene hydrogelation using eosin‐Y as the only photoinitiator” Macromolecular rapid communications, 34(3), 269-273; Lim et al. (2016) “New visible-light photoinitiating system for improved print fidelity in gelatin-based bioinks” ACS biomaterials science & engineering, 2(10), 1752-1762; and Zeiger et al. (2013) “Why the dish makes a difference: quantitative comparison of polystyrene culture surfaces” Acta biomaterialia, 9(7), 7354-7361, as applied to claims 16-18, 22-24, and 26 above; in further view of US 2015/0291929 A1 to Murphy et al.
Regarding dependent claim 19, Shih, Lim and Zeiger do not teach generating a 3-dimensional endothelial network comprising said visible light photopolymerized hydrogel, as claimed.
Murphy is relevant prior art for teaching methods of generating hydrogel compositions to promote tubulogenesis of endothelial cells. The invention is useful for promoting tubulogenesis and screening for pro-tubulogenic and anti-tubulogenic agents. The hydrogel composition includes a photoinitiator, a multi-armed poly(ethylene glycol) norbornene, a di-thiol-terminated cross-linker, a cysteine-terminated RGD peptide, and a population of endothelial cells. See, e.g., Abstract; par. 10-14, 75, 78-80, 85, 107.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Shih, Lim and Zeiger combined, as set forth above, by further generating a 3-dimensional endothelial network with said photopolymerized hydrogel, as found in Murphy, with a reasonable expectation of success in order to promote tubulogenesis and screen for pro-tubulogenic and anti-tubulogenic agents.
Regarding dependent claims 20 and 25, Murphy teaches that the endothelial cell is a human umbilical vein endothelial cell (HUVEC) or a human iPS-derived endothelial cell. See, e.g., par. 85, 135, 138.
Regarding dependent claim 21, Murphy teaches generating the hydrogel network on a microcarrier for culture of adherent cells in bioreactors for suspension culture. See, e.g., par. 63, 86.
For these reasons, claims 19-21, and 25 would also have been prima facie obvious over the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631