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
The instant application was filed 21 August 2023 and is the national stage entry of PCT/IB2022/051635 filed 24 February 2022. The Applicant claims priority to foreign application IT102021000004412 filed 25 February 2021. An English copy is published as WO2022180565. Therefore, the effective filing date of the instant application is 25 February 2021.
Examiner’s Note
The Applicant's amendments and arguments filed 10 March 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections
not reiterated from previous office actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 10 March 2026, it is noted that claims 1, 3, and 5 have been amended and claim 22 has been newly added. Amendments have been made for clarification purposes and support for the new claim can be found from the current claims under examination. No new matter has been added.
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.
Claim(s) 1-3, 5-7, 10, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107998449 A), Bierhansl et al. (Central Role of Metabolism in Endothelial Cell Function and Vascular Disease, Physiology, 2017), irwreagents.com, and aatbio.com.
Dong teaches a 3D printing ink material (abs) for extrusion (pg. 3) comprising 2-30% silk fibroin (pg. 3, para. 5), 2-30% gelatin (pg. 3, para. 4), 0.5-20% alginic acid (pg. 3, para. 4), 1 g/mL of a glycerol solution (Example 4), 0.1-50% hydrophilic biomaterial, such as chitosan, cellulose, hyaluronic acid, etc. (pg. 3, para. 10-11), which is interpreted as hydrophilic polysaccharides as the controlled density solution, addressing claims 1 and 6. The solution formed from copolymers, such as 0.5-20% alginic acid solution (pg. 3, paras. 4-8; pg. 2, para. 10), is also interpreted as being a controlled density solution (instant specification, pg. 6, lns. 25-30) in claims 1 and 6. The ranges of amounts for gelatin, alginic acid, and silk fibroin fits into the claimed ratio ranges in claim 1. The composition does not require xylitol and may instead include glycerol, which is a suitable glucose analogue (instant specification, pg. 6). The composition further includes endothelial cells (Example 4), which is interpreted as addressing extrusion for hematopoietic lineage cells in claim 1 and also addressing claim 2. Cell concentration may be 0.5-300 million/mL, addressing claims 3 and 22. In certain embodiments, sodium alginate and a temperature of 37 °C are used (Example 4), addressing claims 5 and 10.
Dong does not specifically teach use of a buffer for claims 1 and 7. Dong also does not specifically teach glucose in claim 1.
Bierhansl teaches that endothelial cells use glucose as the main energy source for vessel and tissue formation (pg. 127). Glucose is also interpreted as addressing the limitation of entering the glycolysis cycle (Bierhansl, pg. 127; instant specification, pg. 6).
Itwreagents.com teaches that HEPES is a common buffer used in cell cultures, biochemical, molecular biological, and microbiological purposes because of their favorable properties and stability (pg. 3).
Aatbio.com teaches that phosphate buffers are commonly and popularly used in biological experiments, molecular and cell biology, chemistry, and material science due to its water solubility and high buffering capacity (pg. 1).
Since Dong does not specifically use glucose in their composition in claim 1, one of ordinary skill in the art would have been motivated to use Bierhansl’s teaching that glucose is the main energy source for endothelial cells, with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings in order to improve the stability or success of Dong’s biological ink composition.
Since Dong does not specify using buffers in their formulation in claims 1 and 7, one of ordinary skill in the art would have been motivated to use itwreagents.com’s and aatbio.com’s teachings of HEPES and a saline buffer, such as PBS, with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since Dong’s composition uses cellular and biological material for tissue applications.
In regards to the amounts of components in claim 1, Dong teaches 1 g/mL of a glycerol solution (Example 4) and a skilled artisan would be able to adjust the amount of pH to the desired volume and concentration. That being said and in lieu of objective evidence of unexpected results, the amounts can be viewed as a variable that achieves the recognized result of successfully making the bioink composition. The optimum or workable range of the amounts can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of the components as nonobvious.
Claim(s) 1-7, 10, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107998449 A), Bierhansl et al. (Central Role of Metabolism in Endothelial Cell Function and Vascular Disease, Physiology, 2017), irwreagents.com, aatbio.com, and Olijve (Bioink document).
In regards to claim(s) 1-3, 5-7, 10, 22, Dong et al., as applied supra, is herein applied in its entirety for its teachings of a 3D printing ink material comprising silk fibroin, gelatin, alginic acid, a glycerol solution, and a hydrophilic biomaterial.
Dong does not specifically teach type A or type B gelatin in claim 4.
Olijve teaches that gelatins used in pharmaceutical applications are either type A or type B (pg. 3).
Since Dong does not specifically teach type A or type B collagen in claim 4, but does teach gelatin as a partially hydrolyzed product of collagen (pg. 3, para. 2), one of ordinary skill in the art would have been motivated to use Olijve’s teaching that the pharmaceutical industry uses either type A or type B collagen with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since Dong’s teaching uses gelatin for pharmaceutical applications.
Claim(s) 1-8, 10, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107998449 A), Bierhansl et al. (Central Role of Metabolism in Endothelial Cell Function and Vascular Disease, Physiology, 2017), irwreagents.com, aatbio.com, Olijve (Bioink document), and Oliveira (Advances in bioinks and in vivo imaging of biomaterials for CNS applications, Acta Biomaterialia, 2019).
In regards to claim(s) 1-7, 10, 22, Dong et al., as applied supra, is herein applied in its entirety for its teachings of a 3D printing ink material comprising silk fibroin, gelatin, alginic acid, a glycerol solution, and a hydrophilic biomaterial.
Dong does not specifically teach contrast agents in claim 8.
Oliveira teaches bioprinted scaffolds and contrast agents blended into bioink to produce multifunctional biomaterials (pg. 61).
Since Dong does not specifically teach contrast agents in claim 8, one of ordinary skill in the art would have been motivated to use Oliveira’s teaching of incorporating contrast agents into bioink to produce multifunctional biomaterials with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings to improve and enhance the functionality of Dong’s composition for 3D printing of tissues and organs.
Claim(s) 1-10, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107998449 A), Bierhansl et al. (Central Role of Metabolism in Endothelial Cell Function and Vascular Disease, Physiology, 2017), irwreagents.com, aatbio.com, Olijve (Bioink document), Oliveira (Advances in bioinks and in vivo imaging of biomaterials for CNS applications, Acta Biomaterialia, 2019), and Seyedmahmoud (3D Bioprinting Technologies for Tissue Engineering: A Mini Review, HSOA Journal of Stem Cells Research, Development & Therapy, 2020).
In regards to claim(s) 1-8, 10, 22, Dong et al., as applied supra, is herein applied in its entirety for its teachings of a 3D printing ink material comprising silk fibroin, gelatin, alginic acid, a glycerol solution, and a hydrophilic biomaterial.
Dong does not specifically teach a sterile formulation in claim 9.
Seyedmahmoud teaches that for 3D bioprinted materials, a sterile environment is required (pg. 14).
Since Dong does not specifically teach a sterile formulation in claim 9, one of ordinary skill in the art would have been motivated to use Seyedmahmoud’s teaching of using a sterile environment to make 3D bioprinted materials with a reasonable expectation of success. A skilled artisan would have recognized the need for a sterile environment to prevent contamination for a successful implantation of the biomaterial.
Response to Arguments
Applicant's arguments filed 10 March 2026 have been fully considered but they are not persuasive.
The Applicant argues that Dong does not teach a bioink designed around hematopoietic biology (Remarks, pg. 8).
Applicant’s argument is not found persuasive. Dong teaches a 3D printing ink material (abs) for extrusion (pg. 3) comprising 2-30% silk fibroin (pg. 3, para. 5), 2-30% gelatin (pg. 3, para. 4), 0.5-20% alginic acid (pg. 3, para. 4), 1 g/mL of a glycerol solution (Example 4), 0.1-50% hydrophilic biomaterial, such as chitosan, cellulose, hyaluronic acid, etc. (pg. 3, para. 10-11). Instant claim 1 also recites “a bioink formulation” and “a bioink designed around hematopoietic biology” is interpreted as intended use and is given minimal patentable weight. See MPEP 2111.02(II).
The Applicant argues that Dong does not teach glucose with a specific biological meaning (Remarks, pg. 8).
Applicant’s argument is not found persuasive. Since Dong does not specifically use glucose in their composition in claim 1, one of ordinary skill in the art would have been motivated to use Bierhansl’s teaching that glucose is the main energy source for endothelial cells, with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings in order to improve the stability or success of Dong’s biological ink composition.
The Applicant argues that Dong does not teach that adding a specific buffer and controlled density and glucose combination would be beneficial (Remarks, pg. 8).
Applicant’s argument is not found persuasive. Since Dong does not specify using buffers in their formulation in claims 1 and 7, one of ordinary skill in the art would have been motivated to use itwreagents.com’s and aatbio.com’s teachings of HEPES and a saline buffer, such as PBS, with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since Dong’s composition uses cellular and biological material for tissue applications.
The Applicant is encouraged to provide any unexpected results regarding the allegedly beneficial combination of the specific components.
The Applicant argues that Dong does not teach the limitation of “suitable for extrusion with hematopoietic lineage cells” in claim 1 (Remarks, pg. 9).
Applicant’s argument is not found persuasive. Dong’s composition further includes endothelial cells (Example 4), which is interpreted as addressing extrusion for hematopoietic lineage cells in claim 1.
The Applicant argues that the secondary references do not discuss bioinks and that stating that HEPES is a known buffering agent does not provide motivation to use in Dong’s teaching (Remarks, pgs. 9-10).
Applicant’s argument is not found persuasive. Since Dong does not specify using buffers in their formulation in claims 1 and 7, one of ordinary skill in the art would have been motivated to use itwreagents.com’s and aatbio.com’s teachings of HEPES and a saline buffer, such as PBS, with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since Dong’s composition uses cellular and biological material for tissue applications. Furthermore, since HEPES is a buffer that is well-known in the art and commonly used, it is obvious to a skilled artisan to adjust particular conventional working conditions that is well within the purview of the skilled artisan.
The Applicant argues that the combination of ingredients results in a synergistic effect (Remarks, pg. 10).
Applicant’s argument is not found persuasive. To show synergy, the applicant must prove the invention exhibits more than mere additive effects. The effectiveness of the combination should be shown vs. the individual components, and the effectiveness also should be shown over what the closest cited prior art suggests.
The Applicant argues that a general disclosure regarding gelatin from Olijve and contrast agents from Oliveira does not mean a skilled artisan would have been led to modify the teachings to arrive at the claimed invention (Remarks, pg. 11).
Applicant’s argument is not found persuasive. Since Dong does not specifically teach type A or type B collagen in claim 4, but does teach gelatin as a partially hydrolyzed product of collagen (pg. 3, para. 2), one of ordinary skill in the art would have been motivated to use Olijve’s teaching that the pharmaceutical industry uses either type A or type B collagen with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings since Dong’s teaching uses gelatin for pharmaceutical applications.
Furthermore, since Dong does not specifically teach contrast agents in claim 8, one of ordinary skill in the art would have been motivated to use Oliveira’s teaching of incorporating contrast agents into bioink to produce multifunctional biomaterials with a reasonable expectation of success. A skilled artisan would have been led to combine the teachings to improve and enhance the functionality of Dong’s composition for 3D printing of tissues and organs.
Therefore, a skilled artisan would have been easily motivated to use Olijve’s and Oliveira’s teachings as a way to improve the composition taught by Dong. It is also obvious to a skilled artisan to adjust particular conventional working conditions that is well within the purview of the skilled artisan.
The Applicant argues that introducing additional agents would cause loss of functionality (Remarks, pg. 11).
Applicant’s argument is not found persuasive. The applicant is encouraged to expand upon any alleged unexpected results regarding the preservation of activity of key components.
The Applicant argues that Seyedmahmoud teaches a sterile environment, which differs from a sterile formulation (Remarks, pgs. 11-12).
Applicant’s argument is not found persuasive. Seyedmahmoud teaches that for 3D bioprinted materials, a sterile environment is required (pg. 14). A sterile environment is interpreted as all-encompassing, which includes a sterile formulation. Additionally, a skilled artisan would be able to reasonably understand and conclude that a sterile formulation would be desirable in sterile environment.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danielle Kim whose telephone number is (571)272-2035. The examiner can normally be reached M-F: 9-5 p.m. PST.
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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