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 .
Applicant’s response filed on 05/27/2026 is acknowledged and has been entered into the application file.
Claims 1-10 were pending in the instant application. Claim 3 is cancelled. Claims 1-2, and 4-10 are currently pending and under examination in the instant application.
This action is a second non-final rejection.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1, 3-10 under 35 U.S.C. 103 as being unpatentable over Hyun-wook et al. (KR101954953B1), in view of STEINBACH-RANKINS et al. (WO2022082027A1), and Kuo et al. (Kuo et al., “An integrated manufacturing strategy to fabricate delivery system using gelatin/alginate hybrid hydrogels: 3D printing and freeze-drying”. Food Hydrocolloids, Volume 111, 2021):
Applicants have traversed the rejection asserting that Hyun-Wook fails to disclose "a content of the extracellular matrix composition in the bio-ink is from 92 wt% to 95 wt%. Applicants specifically argue that Hyun-Wook specifically teaches that the content of dECM in the bio-ink is less than 10 wt% and one of ordinary skill in the art would not have had a reasonable expectation of success in increasing the dECM content from less than 10 wt% to as high as 92 wt% to 95 wt% while still maintaining a functional bio-ink.
Applicant’s arguments, filed on 05/27/2026, with respect to claims 1, 4-10 have been fully considered and are persuasive. The rejection of claims 1 and 4-10 has been withdrawn.
RE: Rejection of Claim(s) 1-2 under 35 U.S.C. 103 as being unpatentable over Hyun-wook et al. (KR101954953B1), in view of STEINBACH-RANKINS et al. (WO2022082027A1), and Kuo et al., and further in view of Zhang et al.:
Applicants have traversed the rejection asserting that neither Hyun-Wook nor Zhang, alone or in combination, discloses or suggests the subject matter of claim 2, such that Zhang et l. fails to disclose the features of "cell culture" and "de-crosslinking treatment" recited in claim 2.
Applicant’s arguments, filed on 05/27/2026, with respect to claims 1-2 have been fully considered and are persuasive. The rejection of claims 1-2 has been withdrawn.
New/Maintained Rejections
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.
Claim(s) 1-2, 4-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hyun-wook et al. (KR101954953B1. Citations are from the English Translation of KR101954953B1), in view of STEINBACH-RANKINS et al. (WO2022082027A1), Kuo et al. (Kuo et al., “An integrated manufacturing strategy to fabricate delivery system using gelatin/alginate hybrid hydrogels: 3D printing and freeze-drying”. Food Hydrocolloids, Volume 111, 2021), and Zhang et al. (Zhang et al. "Research progress in decellularized extracellular matrix-derived hydrogels". Regen Ther. 2021 May 18;18:88-96).
Regrading claim 1, Hyun-wook et al. teaches a method for manufacturing a sterile bio-ink comprising providing an extracellular matrix composition, adding an animal-based gel, and mixing the extracellular matrix composition, the gels to obtain a gel mixture, and centrifuging and degassing the gel mixture to obtain the bio-ink (page 3, last paragraph, page 4, first paragraph, and Example 1-1: Manufacture of gelatin-based bio-ink and Example 1-4:Degassed Extracellular Substrate-based bio-ink (dECM based bio-ink and its viscosity analysis on page 5).
However, Hyun-wook et al. fails to teach that the extracellular matrix composition is in a liquid state. Hyun-wook et al. also fails to teach adding a plant-based gel and that the gels are freeze-dried. Also, Hyun-wook et al. does not teach the content of the extracellular matrix composition in the bio-ink of 92% wt to 95% wt
However, STEINBACH-RANKINS et al. teaches using decellularized extracellular matrix hydrogel, animal-based gel (gelatin) and plant-based gel (alginate) in making bioinks (claims 7-9 of STEINBACH-RANKINS et al.). STEINBACH-RANKINS et al. also teaches that gelatin and alginate are both attractive for use in 3D bioprinting because they are biocompatible and bioinert. Bioinks that include gelatin and alginate have demonstrated printability, cell viability, proliferation, adhesion, and release of cell specific markers within the scaffold (page 6, lines 21-27).
Also, Kuo et al. provides motivation to freeze dry the animal-based gel and the plant-based gel before filtering them to the extracellular matrix composition. Kuo et al. specifically teaches combining 3D printed bioscaffold with freeze-drying to enhance the mechanical properties by increasing the porosity and improving the surface area, without impacting the bioavailability of uploaded cells (page 6, column 2, paragraph 1). Kuo et al. also teaches freeze-drying gelatin/alginate hybrid hydrogel during the preparation of bioinks primarily to enhance the structural integrity, improve printability, and increase the porosity of the final scaffold (3.2. 3D printing and freeze-drying of gelatin/alginate hybrid hydrogel on page 5).
Furthermore, Zhang et al. teaches decellularized extracellular matrix (dECM) has become a promising material with the unique ability to maintain both biochemical and topographical micro-environments of native tissues. The results show that the bioprinted human kidney cells in the KdECMMA bioink are highly viable and mature with time (Section 4.1.4. Decellularized ECM-derived bioinks). Therefore, Zhang et al. provides motivation to increase the ECM content in the Bioink composition.
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art to have used plant-based gel, such as alginate in the method of making the sterile bioink of Hyun-wook et al. with a reasonable expectation of success. One would have been motivated to have done so since bioinks that include both animal-based gel (gelatin) and plant-based gel (alginate) demonstrates printability, cell viability, proliferation, adhesion, and release of cell specific markers within the scaffold as taught by STEINBACH-RANKINS et al.
Additionally, it would have been prima facie obvious to one of the ordinary skills in the art to have freeze-dried the animal-based gel (gelatin) and plant-based gel (alginate) before dissolving it on the ECM in the process of manufacturing the bioink of Hyun-wook et al. with a reasonable expectation of success. One would have been motivated to have done so since to enhance the structural integrity, improve printability, and increase the porosity of the final scaffold as taught by Kuo et al.
Also, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have modified the content of the extracellular matrix composition in the bio-ink of Hyun-wook et al. such that it is from 92% wt to 95% wt with a reasonable expectation of success. One would have been motivated to have optimized the content of the extracellular matrix composition in the method of Hyun-wook et al. to assist in cellular differentiation since the content of the ECM in the bioink would have required only routine experimentation.
Regarding claim 2: Following discussion of claim 1 above, Hyun-wook et al. fails to teach how the ECM is manufactured.
However, Zhang et al. teaches making a decellularized extracellular matrix composition by providing a gel, carrying out a crosslinking treatment, wherein the crosslinking treatment includes adding a crosslinking agent to the gel to obtain a crosslinked gel, carrying out a cell culture, wherein the cell culture includes implanting cells on the crosslinked gel and incubating the cells by adding a culture solution, carrying out a decrosslinking treatment, wherein the decrosslinking treatment includes adding a decrosslinking agent to the crosslinked gel to obtain a decrosslinked mixture, and carrying out an extraction treatment, wherein the extraction treatment includes adding a lysis enzyme to the decrosslinked mixture and filtering the decrosslinked mixture to obtain the extracellular matrix composition (3.2. dECM hydrogel formations on page 90, column 1).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art to have made the decellularized extracellular matrix composition according to the method of Zhang et al. and used it in the process of manufacturing the bioink of Hyun-wook et al. with a reasonable expectation of success. One would have been motivated to have done so since dECM hydrogels have the following advantages, such as injectability and having inherent biological activity of the natural matrix and adjustability of mechanical properties as taught by Zhang et al.
Regarding claim 4: Following discussion of claim 1 above, Hyun-wook et al. further teaches that the animal-based gel is gelatin (page 3, paragraph 7).
Regarding claim 5: Following discussion of claim 1 above, STEINBACH-RANKINS et al. further teaches that the plant-based gel is sodium alginate (claims 16-17).
Regarding claim 6: Following discussion of claim 1 above, STEINBACH-RANKINS et al. further teaches that the bio-ink contains from about 3 wt% to 4 wt% of the plant-based gel (page 7, lines 30-32).
Regarding claim 7: Following discussion of claim 1 above, STEINBACH-RANKINS et al. further teaches that the bio-ink contains from about 2 wt% to 4 wt% of the animal-based gel (page 7, lines 30-32).
Regarding claim 8: Following discussion of claim 1 above, Hyun-wook et al. does not specifically teach the weight ratio of the extracellular matrix composition, the plant-based gel, and the animal-based gel ranges from 100:3.5:2 to 100:3.5:4. However, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have modified the content of the extracellular matrix composition in the bio-ink of Hyun-wook et al. such that it is from 92% wt to 95% wt with a reasonable expectation of success. One would have been motivated to have optimized the content of the extracellular matrix composition in the method of Hyun-wook et al. to provide a more suitable growth environment for cells, and more effectively assists in cellular differentiation since the content of the ECM in the bioink would have required only routine experimentation.
Regarding claim 9: Following discussion of claim 1 above, Hyun-wook et al. further teaches that the bioink is highly transparent gel (page 3, paragraph 4). Hyun-wook et al. does not specifically teach the bio-ink has a light transmission rate that is greater than or equal to 70%. However, it would have been prima facie obvious to one of the ordinary skills in the art before the effective filing date of the claimed invention to have modified the light transmission rate of the bio-ink of Hyun-wook et al. such that it is greater than or equal to 70%. with a reasonable expectation of success. One would have been motivated to have optimized the light transmission rate of the bioink of Hyun-wook et al. to have good printability and to be used for printing a transparent printing product since the light transmission rate of the bioink would have required only routine experimentation.
Regarding claim 10: Following discussion of claim 1 above, Hyun-wook et al. further teaches in Figure 5 that viscosity of the bio-ink ranges from 1 Pa-s to 20,000 Pa-s.
Conclusion
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
