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 .
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 209-214 and 216-226 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kang et al. (US 2019/0328935 A1)
Regarding claim 209: Kang et al. discloses an artificial tissue progenitor comprising a solid support and microcapsules comprising cells within the solid support. (57) In a preferred embodiment of the invention, the microcapsule comprising the cells is a hydrogel (0240) In addition to this, Kang specifies a preferred embodiment of the invention in which the biodegradable material used for the preparation of the microcapsule is a modified gelatin cross-linked with dialdehyde starch (hereafter DAS). (0269)
Regarding claim 210: Kang discloses a preferred embodiment in which the biodegradable material selected for the capsule is collagen, specifically type 1, 2, or 3. (0277)
Regarding claims 211 and 212: Kang discloses a preferred embodiment of use of a 3D bioprinter to create the microcapsules which involves creation of the biological construct via 3D bio-printer and comprises multiple printing heads for the various components of the construct. (0402-0409) In addition to this, Kang discloses an example of the invention in which collagen type 1 is used as the carrier of a bio-ink. (0818) This reads both on claim 211 of use of a bio ink, as the complete construct is achieved via bioprinting and therefore would comprise both the scaffolding components and cells, and claim 212 regarding use of a 3D printer.
Regarding claim 213: A person of ordinary skill in the art would recognize that collagen types 1, 2, and 3 are present in the extracellular matrix, therefore the use of collagen types 1, 2, or 3 as discussed above read on use of extracellular matrix in the composition.
Regarding claim 214: Kang discloses a preferred embodiment of the invention which uses osteoblasts, chondrocytes, fibroblasts, and a variety of other cells as part of the composition of the invention. (0250)
Regarding claim 216: Kang discloses a preferred embodiment of the invention in which a first ink made of the complete microcapsules with a second ink comprising an adhesive effect layered to create a three dimensional construct. (0488-0491) Kang further discloses a preferred embodiment of the invention in which the cells within the microcapsules are able to migrate through the adhesive layer of the composition, migrating and growing throughout the construct. (0540) This reads on the population of cells being evenly distributed throughout the construct, and further reads on the cells comprising at least 10% of the hydrogel, as the microcapsules comprising the cells are layered repeatedly with the adhesive, in effect comprising 50% of the construct.
Regarding claim 217: Kang discloses that the viscosity of the gel should be suitable for drawing a pattern or coating. (0214) This reads on the hydrogel being a viscous gel, as it must be thick enough to hold its shape during printing.
Regarding claim 218: Kang discloses a preferred embodiment wherein the viscosity can be between 1-1000 pascal seconds, which when converted to centipoise is 1000-1000000 centipoise. While the range disclosed by Kang is larger than the claimed range, the claimed range lies inside of the range disclosed by Kang, making it prima facie obvious that the disclosed art reads on claim 218.
As stated in MPEP 2144.05.1, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Regarding claim 219: Kang discloses a preferred embodiment of the invention in which the mechanical strength of the construct is 100 kPa. (0594)
Regarding claims 220 and 221: Kang discloses a preferred embodiment of the invention in which the microcapsule comprises an additional agent such as a cytokine (0286), specifically a growth factor such as fibroblast growth factor. (0291)
Regarding claim 222: Kang discloses a preferred embodiment of the invention which uses heparin as the biodegradable material for the microcapsule. (0269)
Regarding claim 223: Kang discloses a preferred embodiment of the invention which uses starch as the biodegradable material for the microcapsule. (0269)
Regarding claim 224: Kang discloses a preferred embodiment of the invention which uses gelatin as the biodegradable material for the microcapsule. (0269)
Regarding claims 225: Kang discloses a preferred embodiment of the invention comprising the method of having a first ink made of the complete microcapsules with a second ink comprising an adhesive effect layered to create a three dimensional construct (0488-0491) that is printed in multiple layers, in some instances at least 500 layers. (0493-0495) In a different preferred embodiment of the invention, an adhesive layer is sprayed onto the surface of a biological construct, cell culture medium is dropped onto the adhesive layer, and the adhesive is sprayed again, layering the process until the desired thickness is achieved to create a biological construct. (0510-0515) In either example, multiple layers of a first and second composition are deposited and the layers comprise different mechanical and biological properties.
Regarding claim 226: Kang discloses a preferred embodiment of the microcapsule to be comprised of a modified gelatin cross-linked with DAS (0269), includes cells in the microcapsule (0250), and collagen is selected as the biodegradable material used for the preparation of the microcapsule. (0269)
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 215 is rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (US 2019/0328935 A1) in view of McGuigan et al. (Modular tissue engineering: fabrication of a gelatin-based construct, 2007)
The teachings of Kang are disclosed above. Kang fails to teach use of a randomized distribution of cells in a 3D construct, as Kang teaches layered, organized printing.
Regarding claim 215: Kang teaches the formation of a layered construct comprising microcapsules (hydrogels) evenly distributed throughout the construct, as disclosed above. Kang further teaches layering of adhesive with the microcapsules, reading on the cells comprising at least 10% of the hydrogel, as the microcapsules comprising the cells are layered repeatedly with the adhesive, in effect comprising 50% of the construct.
Kang fails to teach a randomized distribution of hydrogels comprising cells within the construct. McGuigan teaches methods of creating modular tissue-engineered constructs which are permeated by a network of interconnected, endothelial cell-lined channels to facilitate blood and nutrient perfusion and delivery. (Pg 136, Abstract) To achieve this, human hepatocytes were encapsulated in short collagen modules and then randomly assembled into a larger tube to form a construct. The interstitial spaces generated by the random assembly allowed for interconnected channels which permeated the construct, allowing for fluid perfusion. (Pg 137, Introduction)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kang with the teachings of McGuigan of use of a random array of cells within the hydrogel. A person of ordinary skill in the art would have been motivated and had a reasonable expectation of success at doing so based on the teachings of McGuigan, who state that the random array of micro collagen encapsulated cell clusters allows for the formation of channels for fluid to flow through, allowing for permeation of nutrients throughout the construct.
Claims 227-228 are rejected under 35 U.S.C. 103 as being unpatentable over Kang et al. (US 2019/0328935 A1) in view of Nair et al. (Crosslinking Collagen Constructs: Achieving Cellular Selectivity Through Modifications of Physical and Chemical Properties, 2020)
Regarding claim 227: As Kang teaches a preferred embodiment of the invention wherein the microcapsule can comprise collagen, cross-linked DAS, or a combination thereof, this reads on the hydrogel comprising both collagen and DAS. Kang fails to disclose cross linking of the collagen itself into the hydrogel.
Nair teaches that cross linking of collagen improves its strength, stiffness, and stability (Pg 1, Abstract) and that the fundamental goal of chemical crosslinking is to improve the mechanical properties and stability of the final processed collagen product. (Pg 1, Section 2)
Regarding claim 228: Following the discussion regarding claim 227 above, Kang teaches a preferred embodiment of the invention comprising the method of having a first ink made of the complete microcapsules with a second ink comprising an adhesive effect layered to create a three dimensional construct (0488-0491) that is printed in multiple layers, in some instances at least 500 layers. (0493-0495) In a different preferred embodiment of the invention, an adhesive layer is sprayed onto the surface of a biological construct, cell culture medium is dropped onto the adhesive layer, and the adhesive is sprayed again, layering the process until the desired thickness is achieved to create a biological construct. (0510-0515) In either example, multiple layers of a first and second composition are deposited and the layers comprise different mechanical and biological properties. However, Kang fails to disclose cross linking collagen into the hydrogel.
Nair teaches that cross linking of collagen improves its strength, stiffness, and stability (Pg 1, Abstract) and that the fundamental goal of chemical crosslinking is to improve the mechanical properties and stability of the final processed collagen product. (Pg 1, Section 2)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Kang with the teachings of Nair regarding the benefits of cross linking collagen hydrogels. A person of ordinary skill in the art would have been motivated and had a reasonable expectation of success due to the teachings of Nair, who teach that cross linking collagen improves the mechanical properties and stability of the finished collagen product.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/HANNA MARIE THUESON/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638