The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of Group I, claims 1-16, in the reply filed on November 10, 2025 is acknowledged.
Claims 17-18 are canceled. Claims 1-16 are under consideration.
Priority: This application is a 371 of PCT/US2022/048912, filed November 4, 2022, which claims benefit of provisional application 63/275565, filed November 4, 2021.
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 1-2, 8-11, 13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffner et al. (2017 Sci Adv 3(12):eaao6804, 9 pages) in view of Qian et al. (US 20200109299; IDS 05.03.24). Schaffner et al. disclose 3D printing of bacteria into functional complex materials by embedding bacteria in a biocompatible and functionalized 3D printing ink and printing “living materials” or “Flinks” (at least p. 1-2, also Fig. 1). Schaffner et al. disclose a method for 3D printing of Flinks comprising providing an ink composition comprising sodium hyaluronate (HA) functionalized with glycidyl methacrylate (GM), a solvent, bacteria, and Irgacure 2959 (a photoinitiator) (at least p. 7-8), 3D printing a pattern in a hydrogel support matrix using the ink composition in a container, and forming a Flink material comprising the living bacteria by curing the printed material (at least p. 2 Fig. 1, p. 7-8). Schaffner et al. differ from the method of instant claim 1 by not explicitly teaching a monomer.
Qian et al. also disclose methods for making a living structure from a bio-ink material of living freeze-dried cells, the bio-ink material comprising fillers, binders, and a photoinitiator (at least abstract, paragraphs 0148-0170). Qian et al. disclose in some embodiments, the bio-ink comprises the cells and more than one filler component (at least paragraphs 0062-0063), the filler further comprises a binder, the binder is an oligomer, monomer, or mixtures thereof, where the filler further comprises a photo-initiator that absorbs light and initiates photopolymerization of the binder material (i.e. the oligomer and/or monomer) (at least paragraph 0064).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a polymerizable monomer of Qian et al. for the polymer in the ink composition provided in the method of 3D printing a living material comprising bacteria of Schaffner et al. noted above, to thereby arrive at the claimed method for 3D printing living materials comprising providing an ink composition comprising a polymerizable monomer, a crosslinking agent, a photoinitiator, and a solvent, 3D printing a pattern in a hydrogel support matrix using the ink composition in a container, and forming a 3D printed living material comprising the living bacteria by curing the printed living material (instant claim 1). The motivation to do so is given by the prior art, which disclose ink compositions for 3D printing comprises materials including monomers, polymers, and/or oligomers. One of ordinary skill would have a reasonable expectation of success because the prior art discloses materials for ink compositions utilized in 3D printing of living materials are known.
Regarding instant claim 2, Schaffner et al. disclose bacteria is in the printed 3D living material (at least p. 1-2, also Fig. 1) and Qian et al. also disclose cells in the living material are microbes, in some embodiments, the microbes include bacteria and are E. coli, or the microbes include yeast and are S. cerevisiae (at least paragraph 0053). Therefore, it would be obvious to one of ordinary skill that the bacteria in the ink composition for 3D printing a living material is selected to be E. coli.
Regarding instant claim 8, Schaffner et al. disclose the photoinitiator Irgacure 2959 is 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (p. 7) and Qian et al. also disclose suitable photo-initiators include Irgacures (at least paragraph 0064). Therefore, it would be obvious to one of ordinary skill to arrive at the recited 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone photoinitiator in the ink composition for 3D printing a living material.
Regarding instant claim 9, Schaffner et al. disclose mixing the components to form the ink composition (at least p. 7) and Qian et al. also disclose mixing the components to form the bio-ink composition (at least paragraphs 0111-0115). Therefore, it would be obvious to one of ordinary skill to mix the components of the ink composition comprising a polymerizable monomer, cross-linking agent, photoinitiator, and solvent of Schaffner et al. in view of Qian et al. noted above.
Regarding instant claims 10-11, Qian et al. disclose in some embodiments, the bio-ink comprises more than one filler component, where the filler component is alginate (at least paragraph 0061). Therefore, it would be obvious to one of ordinary skill to further include an additional polymer, the polymer being alginate, in the ink composition comprising a polymerizable monomer, cross-linking agent, photoinitiator, and solvent noted above.
Regarding instant claim 13, Schaffner et al. disclose curing the Flinks comprising photoinitiator with light (at least p. 7) and Qian et al. disclose activating the photoinitiator by irradiation with ultraviolet (UV) light (at least paragraph 0064). Therefore, it would be obvious to one of ordinary skill to arrive at the recited curing the 3D printed pattern with at least one wavelength of light to activate the photoinitiator.
Claims 1-2, 6-7, 8-11, 13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffner et al. (2017 Sci Adv 3(12):eaao6804, 9 pages) in view of Qian et al. (US 20200109299; IDS 05.03.24) and Zhu et al. (2020 Sci Adv 6:eaba5575, 10 pages). The teachings of Schaffner et al. and Qian et al. over at least instant claims 1-2, 8-11, 13 are noted above.
Regarding instant claims 6-7, Qian et al. disclose that the bio-ink composition comprises a polymerizable monomer (at least paragraph 0064). Zhu et al. disclose an ink composition comprising acrylamide as the monomer, N,N’-methylenebisacrylamide as the cross-linker, and a photo-initiator (at least p. 8). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the acrylamide and N,N’-methylenebisacrylamide of Zhu et al. for the monomer and crosslinking agent in the ink composition of Schaffner et al. in view of Qian et al. noted above in the method of 3D printing a living material, to thereby arrive at the claimed method for 3D printing living materials comprising providing an ink composition comprising a acrylamide, N,N’-methylenebisacrylamide, a photoinitiator, and a solvent, 3D printing a pattern in a hydrogel support matrix using the ink composition in a container, and forming a 3D printed living material comprising the living bacteria by curing the printed living material (instant claims 6-7). The motivation to do so is given by the prior art, which disclose ink compositions for 3D printing comprises materials including monomers, where acrylamide is a known monomer for preparing 3D ink. One of ordinary skill would have a reasonable expectation of success because the prior art discloses materials for ink compositions utilized in 3D printing are known.
Claims 1-2, 3-5, 8-11, 13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffner et al. (2017 Sci Adv 3(12):eaao6804, 9 pages) in view of Qian et al. (US 20200109299; IDS 05.03.24) and Millik et al. (2019 Biofabrication 11:045009, 11 pages). The teachings of Schaffner et al. and Qian et al. over at least instant claims 1-2, 8-11, 13 are noted above.
Regarding instant claims 3-4, Qian et al. disclose the bio-inks comprise a cell density of at least 50 wt% (at least paragraph 0073), in some embodiments, a sample of cells are obtained from a source, isolated, and dried, where prior to drying, the sample of cells is concentrated, by for instance, centrifuging (at least paragraph 0074). Qian et al. disclose the bio-ink comprising the cell granules, solvent, polymer, and photoinitiator, can be loaded into a syringe barrel for printing (at least paragraph 0113). Millik et al. disclose 3D printing for hydrogels (at least p. 1). Millik et al. disclose that prior to using the hydrogel in 3D printing, remaining bubbles are eliminated by centrifugation (at least p. 3-4). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the ink composition of Schaffner et al. in view of Qian et al. noted above can be formed by mixing a pellet having a known cell amount with the ink composition components, centrifuging the ink composition, and loading the centrifuged ink composition into a syringe for injection (instant claims 3-4). The motivation to do so is given by the prior art, which disclose that centrifuging concentrates the components of a composition and eliminates air bubbles. One of ordinary skill would have a reasonable expectation of success because methods and conditions for preparing bioink compositions for 3D printing living materials are known in the prior art.
Regarding instant claim 5, as noted above, Qian et al. disclose that the sample of cells are obtained from a source and centrifuged (at least paragraph 0074). Schaffner et al. disclose that the cells for incorporating or embedding in the bio-ink composition are grown in culture medium (at least p. 8). Schaffner et al. also disclose cultures can be pelleted by centrifugation and suspended in MM for ink preparation or direct inoculation (at least p. 8). Therefore, it would have been obvious to one of ordinary skill that the cells for incorporation into the bioink composition can be prepared in pellet form by inoculating cells into a culture or growth medium, growing the cells in the culture medium, and centrifuging the cells to form a cell pellet (instant claim 5). One of ordinary skill would have a reasonable expectation of success because methods and conditions for preparing bioink compositions for 3D printing living materials are known in the prior art.
Claims 1-2, 3-5, 8-11, 12, 13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffner et al. (2017 Sci Adv 3(12):eaao6804, 9 pages) in view of Qian et al. (US 20200109299; IDS 05.03.24), Millik et al. (2019 Biofabrication 11:045009, 11 pages), and Shoseyov et al. (US 20200179562; IDS 05.03.24). The teachings of Schaffner et al., Qian et al., and Millik et al. over at least instant claims 1-2, 3-5, 8-11, 13 are noted above.
Regarding instant claim 12, Qian et al. disclose that the bio-ink further comprise a hydrogel, where non-limiting examples of hydrogels include alginate (at least paragraph 0070). Qian et al. also disclose that the living structure is biocompatible with a physiological environment without eliciting unwanted and/or adverse effects to the environment (at least paragraph 0079). Shoseyov et al. also disclose material formulations for additive manufacturing or 3D printing (abstract), where 3D printing uses biological materials, optionally in combination with chemicals and/or cells (at least paragraphs 0013), where to allow for control on the curing, the building material commonly includes polymerizable moieties or groups that polymerize upon being dispensed, to preserve the geometric shape and provide the necessary physical properties of the final product (at least paragraph 0016). Shoseyov et al. disclose the receiving medium for the 3D printing is a supporting medium and can be biocompatible material and comprises a hydrogel (at least paragraphs 0117-0120). Shoseyov et al. also disclose the hydrogel is biocompatible, and is such that when a biological moiety is impregnated or accumulated therein, an activity of the biological moiety is maintained (at least paragraph 0326), and where the hydrogel properties are governed by factors including the aqueous media content and composition (at least paragraph 0316). Shoseyov et al. disclose aqueous carriers (or media) comprising a culturing medium (at least paragraph 0296). As noted above, Millik et al. has disclosed in a method for 3D printing, centrifuging eliminates air bubbles (at least p. 6). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further incorporate forming a hydrogel composition by mixing growth medium that is sterile with a thickening agent (i.e. alginate); eliminating bubbles by centrifuging the hydrogel composition; and loading the hydrogel composition into a container for printing in the method of 3D printing a living material of Schaffner et al. in view of Qian et al. noted above (instant claim 12). The motivation to do so is given by the prior art, which disclose bioink compositions can further comprise a hydrogen composition that is biocompatible for the embedded cells; therefore, it would be obvious that a biocompatible hydrogel composition reasonably comprises aqueous medium, including culture medium that is sterile, since the hydrogel functions to maintain a biocompatible environment while maintaining cell activity. One of ordinary skill would have a reasonable expectation of success because methods and conditions for preparing bioink compositions for 3D printing living materials are known in the prior art.
Claims 1-2, 8-11, 13, 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffner et al. (2017 Sci Adv 3(12):eaao6804, 9 pages) in view of Qian et al. (US 20200109299; IDS 05.03.24), Shoseyov et al. (US 20200179562; IDS 05.03.24), and Wang et al. (2018 J Biomed Mater Res Part A:106A: 865-875). The teachings of Schaffner et al. and Qian et al. over at least instant claims 1-2, 8-11, 13, and the teachings of Shoseyov et al. are noted above.
Regarding instant claim 14, Shoseyov et al. disclose that for all technologies, the most important parameter determining the accuracy and efficiency of printing is the static and physical properties of the dispensed building materials, including viscosity and shear-thinning properties (at least paragraph 0018). Shoseyov et al. disclose in some embodiments, material formulations features shear-thinning behavior and/or thermal-thinning behavior (at least paragraphs 0300-0304), where shear-thinning property describes a behavior of a fluidic material that is reflected by a decrease in its viscosity, where thermal-thinning property describes a property of a fluidic material that is reflected by a decrease in its viscosity (at least paragraphs 0302-0303). MPEP 2144.04 notes that design changes are obvious. In this instance, the prior art discloses that the viscosity of hydrogels printed with bioinks can be altered and optimized. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further reduce a viscosity of the 3D printed hydrogel comprising living bacteria in the method of 3D printing a living material of Schaffner et al. in view of Qian et al. noted above, to thereby release the bacteria (instant claim 14), as a matter of design choice. The motivation to do so is given by the prior art Shoseyov et al., which disclose that reduced viscosity is a recognized property for 3D printed hydrogels using bioink. One of ordinary skill would have a reasonable expectation of success because the prior art discloses materials for ink compositions utilized in 3D printing of living materials are known.
Regarding instant claims 15-16, as noted above, Shoseyov et al. disclose that reduced viscosity is a recognized property for 3D printed hydrogels using bioink. Wang et al. disclose that hydrogels fabricated by 3D printing can be eroded by PBS and at 37º C (at least p. 867). Therefore, it would have been obvious to one ordinary skill in the art to reduce the viscosity of the 3D printed hydrogel comprising living bacteria in the method of 3D printing a living material of Schaffner et al. in view of Qian et al. noted above, comprising contacting at least a part of the hydrogel with a buffered solution (PBS) (instant claim 15). The motivation to do so is given by the prior art. Shoseyov et al. disclose that reduced viscosity is a recognized property for 3D printed hydrogels and Wang et al. disclose hydrogel viscosity can be reduced by contact with a buffered solution. One of ordinary skill would have a reasonable expectation of success because the prior art discloses materials for ink compositions utilized in 3D printing are known. Further regarding instant claim 16, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. As noted above, Wang et al. disclose that hydrogels fabricated by 3D printing can be eroded by PBS (at least p. 867). Therefore, it would have been obvious to arrive at the recited 10X phosphate buffered solution by routine optimization. One of ordinary skill would have a reasonable expectation of success because the prior art discloses materials for ink compositions utilized in 3D printing are known.
No claim is allowed.
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/Marsha Tsay/Primary Examiner, Art Unit 1656