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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on 07/01/2022 and 06/23/2023. It is noted, however, that applicant has not filed a certified copy of the applications as required by 37 CFR 1.55.
In the absence of certified priority applications, the priority date is 6/27/2023.
Claims Status
Claims 1-8 are examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 1: The claim recites thickening component and water-repellent component.
A thickening component is interpreted as a component that increases the viscosity of a solution and is very broad. Nucleic acids and proteins are known to increase the viscosity of solutions. Starches, sugars, and gelling agents (such as gelatin, agarose and alginate) also read on “thickening component”.
The instant specification recites 7 species of thickening components (p33).
A water-repellent component is interpreted as a substance that sheds water, repels water or is hydrophobic and is very broad. Plastics, glass, silicone, graphite, waxes, resins, polymers, proteins with hydrophobic residues, lipids and long chain fatty acids all read on “water-repellent component”.
The instant specification recites 6 species of water-repellent components (p29-31).
MPEP 2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention”.
The instant specification fails to support the broad genera of “water-repellent component” and “thickening component” as claimed such that one skilled in the art can reasonably conclude the inventor had possession of the claimed invention.
The gap between the limited number of structures corresponding to those that that are water-repellent components or thickening components described in the instant specification compared to the breadth any water-repellent component and thickening component is extremely large. Given this large gap, the specification fails to support the broad genera of “water-repellent component” and “thickening component” as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Teo et al. (Applied Materials & Interfaces (2019) 12;1-8) in view of Jiang et al. (European Polymer Journal (2018) 112;660-669) and Freeman et al. (Nature (2017) 7;1-12) and as evidenced by IUPAC (Gold Book: Resin [online]. International Union of Pure and Applied Chemistry [retrieved 4/12/2026]. Retrieved from the internet:<URL: https://goldbook.iupac.org/terms/view/RT07166) and Butler et al. (Nanomaterials (2021) 11;2062;1-16) and Fiveable (Amphipathic [online]. Fiveable corporation [retrieved on 04/14/2026]. Retrieved from the Internet: https://fiveable.me/organic-chem/key-terms/amphipathicle).
Regarding claims 1, 3, 7 and 8: Teo teach inkjet printing for hydrogel microstructures by using an hydrogel precursor and a cross-linker with alginate as a model system (abstract). Teo teach sequential inkjet printing, also known as reactive inkjet printing, allows patterning and synthesizing otherwise unprintable and incompatible materials simultaneously (p1 col1 ¶1). Figure 1b teach applying a first liquid application step and a second liquid application step (Fig 1b p2).
Teo teach the first liquid (precursor) comprises sodium alginate dissolved in DI water and the second liquid (cross-linker) comprises CaCl2·6H2O dissolved in DI water (p6 col2 ¶2). CaCl2·6H2O reads on a thickening agent because it cross-links the precursor and thus thickens the combined mixture. As evidenced by Butler(2021) the thickening component (CaCl2·6H2O) in liquid 2 interacts with a component contained in the first liquid (sodium alginate) by replacing the sodium molecules with calcium to form ionic crosslinks (electrostatic interactions) (p5 Fig 3).
Teo do not teach the first liquid comprises a water-repellent component or that the method comprises a staining solution application step.
Lee teach alginate is an anionic polymer (p1 ¶2). Lee further teach amphiphilic alginate derivatives have been synthesized by introducing hydrophobic moieties (e.g. alkyl chains, hydrophobic polymers) and the derivatives can form self-assembled structures such as gels (p3 ¶5).
Fiveable defines amphiphilic as “a molecular or chemical structure that has both hydrophilic (water-loving) and hydrophobic (water-repelling) properties within the same compound” (Fiveable p1). Thus amphipathic alginate comprising hydrophobic moieties reads on a water-repellent component. Lee further teach hydrogels prepared from hydrophobic derivatives of alginate exhibit long-term stability in aqueous media (p4 ¶2).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Teo drawn to a first liquid application step comprising alginate with the teachings of Lee, to use alginate comprising hydrophobic moieties.
One of ordinary skill in the art would have been motivated to modify the method as taught by Teo by using alginate comprising amphiphilic moieties as taught by Lee because Lee teach hydrogels prepared from an alginate thus prepared exhibit long-term stability in aqueous media.
One would have had a reasonable expectation of success because both disclosures are drawn to hydrogels comprising alginate.
Freeman teach a staining solution application step for staining a biological sample. Freeman teach alginate is a commonly used bioink in 3D bioprinting and that stiffness of the hydrogel can effect the fate of mesenchymal stem cells within the bioink (abstract).
Freeman teach 3D bioprinting allows for the development of complex anatomically accurate scaffold geometries that also mimic aspects of the composition and organization of native tissues through the simultaneous deposition of biomaterials, cells, proteins and/or genes in defined locations (p1 ¶1). Freeman teach a main challenge with bioprinting cell laden constructs is identification of an appropriate bioink (hydrogel) which protects cells from damage during printing and provides the appropriate environment (p1 ¶2).
Freeman teach alginate bioinks were prepared to have a cell suspension comprising mesenchymal stem cells (MSCs) (p10 ¶1). Freeman further teach a staining solution application step in which a solution comprising 2uM calcein (cell viability stain) is applied to the cell-laden alginate hydrogel (p10 ¶1). Including cells in the hydrogel and subsequent staining reads on the mixed liquid surrounds a region for holding the staining solution because the staining solution is applied to the hydrogel and thus the hydrogel surrounds a region for holding staining solution.
It would have been obvious to one of ordinary skill in the art to adapt the methods of Teo drawn to a first liquid application step and a second liquid application step by including cells in the hydrogel and a staining application step as taught by Freeman.
One of ordinary skill in the art would have been motivated to modify the method as taught by Teo by including cells in the hydrogel and a cell staining application step, as taught by Freeman, because Freeman teach 3D bioprinting (of hydrogels) allows for the development of scaffolds for tissue engineering, but that the material must protect the cells from damage during printing (p1 ¶1). Thus one would be motivated to include mesenchymal stem cells in the bioink as this represents a promising tissue engineering strategy for replacing, repairing or regenerating damaged tissues and organs (p1 ¶). One would also be motivated to include a cell staining application step, such as applying a calcein viability stain, because one would be motivated to evaluate the ability of the hydrogel to protect the cells from damage during printing.
One would have had a reasonable expectation of success because Freeman teach printing of alginate based hydrogels with MSCs and show successful application of a cell staining step.
Regarding claim 2: The claims recite “resin”. The international union of pure and applied chemistry (IUPAC) define the term resin as “soft solid or highly viscous substance, usually containing prepolymers with reactive groups” (IUPAC - resin (RT07166)).
As discussed supra, Teo teach inkjet printing for hydrogel microstructures by using a hydrogel precursor and a cross-linker with alginate as a model system (abstract). Alginate is a soft solid which comprises prepolymers with reactive groups (COO-; as evidenced by Butler Fig 3) and thus reads on resin as interpreted herein. Alginate is water-soluble and thus reads on the claim limitation as stated.
Regarding claim 4: The claim limitations are in the alternative and thus the claim is interpreted as requiring an anionic resin in the first liquid and polyvalent metal ion in the thickening component.
The teachings of Teo are discussed supra. Teo teach an alginate-based hydrogel. As discussed supra, alginate is considered a resin based on the definition of resin. Alginate comprises COO- groups (as evidenced by Butler Fig 3) and thus reads on the first liquid contains an anionic resin.
Teo teach the thickening component of the second liquid is CaCl2·6H2O (p6 col2 ¶2). CaCl2·6H2O in an aqueous solution and comprises Ca2+ which is a polyvalent metal ion. Thus the disclosure of Teo reads on the thickening component includes at least one polyvalent metal ion.
Regarding claim 6: The teachings of Teo and Lee are discussed above. As discussed supra, alginate is interpreted as a resin.
Lee teach alginate is an anionic polymer (p1 ¶2). Lee further teach amphiphilic alginate derivatives have been synthesized by introducing hydrophobic moieties (e.g. alkyl chains, hydrophobic polymers) and the derivatives can form self-assembled structures such as gels (p3 ¶5). Thus Lee teach a water-repellent component that is an anionic resin. Lee further teach hydrogels prepared from hydrophobic derivatives of alginate exhibit long-term stability in aqueous media (p4 ¶2).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Teo drawn to applying a first liquid comprising alginate and a second liquid comprising CaCl2 onto a substrate by using alginate modified to be hydrophobic as taught by Lee.
One of ordinary skill in the art would have been motivated to modify the method as taught by Teo with a alginate modified to comprise hydrophobic moieties, as taught by Lee, because Lee teach hydrogels prepared from hydrophobic alginate derivatives exhibit long-term stability in aqueous media.
One would have had a reasonable expectation of success because both inventions are drawn to alginate based hydrogels.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over of Teo et al., Jiang et al., Freeman et al. and Lee et al. as applied to claims 1-4 and 6-8 above, and further in view of Tsou et al. (Bioactive Materials (2016) 1:39-55).
Regarding claim 5: The teachings of Teo are discussed supra. Teo do not teach the thickening component includes a water-repellent component.
Freeman teach hydrogels for tissue engineering (p1 ¶1). Freeman further teach the incorporation of VEGF in the hydrogel (p5 ¶2). VEGF is a protein which comprises hydrophobic residues and thus reads on a water-repellent component as required by the instant claim. Freeman teach VEGF is added to the alginate solutions.
It would have been obvious to one of ordinary skill in the art to adapt the methods of Teo drawn to a first liquid application step and a second liquid application step by VEGF in the second liquid application step to incorporate VEGF into the hydrogel as taught by Freeman. It would have been equally obvious to add VEGF to the first liquid application step, the second liquid application step or both liquid application steps because there are a finite number of liquid application steps and adding VEGF to any of the liquid application steps would be equally obvious.
One of ordinary skill in the art would have been motivated to modify the method as taught by Teo by incorporating VEGF into the hydrogel as taught by Freeman because Tsou teach hydrogels comprising VEGF induce robust cell retention when implanted (p48 col1 ¶1).
One would have had a reasonable expectation of success because both disclosures are drawn to hydrogels that can be used for tissue engineering.
Thus the teachings of Teo et al., Jiang et al., Freeman et al., Lee et al., and Tsou et al. render obvious the invention as claimed.
Conclusion
No claims are allowed.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631