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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 20, 21, and 26 – 35 in the reply filed on 06//24/2026 is acknowledged.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Objections
Claim 21 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. See MPEP § 608.01(n). Accordingly, the claim has not been further treated on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 recites the limitation "the composition of claim 1" in line 2 of limitation (b). There is insufficient antecedent basis for this limitation in the claim.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 20, 22-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bondesson et al. (US Pub. No. 2022/0249738 A1), in view of Trujillo et al. (Trujillo, S., et al., Biomaterials, 2020, vol. 252, 120104. doi: 10.1016/j.biomaterials.2020.120104) and Lin and Anseth (Lin, C.-C. et al, Adv. Funct. Mater., 2009, vol. 19, p. 2325-2331), hereafter referred to as Bondesson, Trujillo, and Lin, respectively.
Regarding claim 20, Bondesson discloses a 3D printed skin tissue model and method for making the model capable of automated production, comprised of at least one bioink A, at least one cell type A, at least one factor A. Bondesson discloses the use of biopolymers like methacrylate gelatine (GelMA) and of extracellular matrix components such as laminins and/or fibrinogen in the bioink (pg. 1, [0004, 0009], (e)). The bioink is extruded through a nozzle onto different containers or substrates, including glass, biomaterials, and plastics, as a print bed and can be photocured as a hydrogel during or following the printing process (pgs. 2 – 3, 10, [001, 0024, 0099]). Bondesson does not disclose modifications of the ECM protein.
Trujillo discloses a polyethylene glycol (PEG)-fibronectin hydrogel, where 4-arm PEG is conjugated with maleimide and then attached to fibronectin (FN) with later-alkylated unreacted cysteine residues. The fibronectin-peg conjugates were reacted with thiolated crosslinker, reacting with the terminal maleimide groups. The resulting FN-PEG hydrogels were shown to have increased growth factor (GF) sequestration over their synthetic (PEG only) control (pg. 6 – 7, Fig. 1 – 2, 3.2, par. 1, 3). Additionally, Matrigel-only hydrogels were tested, showing sequestration greater than control but less than the FN-PEG hydrogels (pg. 7, Fig. 2, 3.2, par. 2).
Trujillo notes that FN can promiscuously bind GFs like VEGF through FNIII, but Trujillo’s PEGylated FN structure, while biologically active, seems to have part of the middle FN-III structure blocked by the closely attached PEG (pg. 6, Fig. 1, 3.2). Trujillo additionally discloses that the FN-PEG sequestration of GFs results in exemplary inducement of early cell structures such as sprouting (pg. 9, col. 1, par. 2). Trujillo discloses a hydrogel with an ECM protein with linker L and a blocking group comprised of maleimide, but crosslinks with a thiol crosslinker that binds to maleimide. Additionally, Trujillo does not disclose printing the composition.
Lin tests the bioactivity of hydrogel-bound biotinylated-ligands with AlexaFluor555-labeled streptavidin. Through their testing, Lin finds that the affinity binding reduces after crosslinking the ligand with the PEG hydrogel, especially when the binding site is close to the PEG attachment site (pg. 2327 – 2328, 2.2 – 2.3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated the teachings of Bondesson with the teachings of Trujillo and Lin to create an automatable scaffold production method, including a biocompatible polymer, like GelMA, with hydrogel capability, with a modified ECM like a 4-arm-PEGylated FN with a maleimide, that when photocured according to Bondesson would act as a blocking terminal maleimide, to result in a scaffold that has suspended modified ECM proteins. It would have been obvious to one of ordinary skill in the art to incorporate these ECM proteins, along with the Matrigel-like gelatin structure in GelMA, to highly sequester GFs without hydrogel-attachment hinderance to garner increased early cell activity, as seen in Trujillo and Lin.
Regarding claim 26, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). As discussed, Bondesson teaches the use of GelMA as a biocompatible polymer used in the composition (pg. 1, [0009], (e)).
Regarding claims 27 and 28, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). As discussed, Trujillo teaches the use of fibronectin as an ECM protein employed in the composition (Fig. 1).
Regarding claims 29 and 30, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). As discussed, Trujillo teaches the use of fibronectin as an ECM protein employed in the composition, where the fibronectin is conjugated with 4-arm-PEG-maleimide, where the 4-arm-PEG reads on the claimed synthetic PEG and 4-arm PEG linker (Fig. 1).
Regarding claims 31 and 32, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). As discussed, Bondesson teaches the use of photocuring to crosslink the composition (pg. 10, [0099]) and Trujillo teaches the use of maleimide as the terminal group before crosslinking (Fig. 1). When modifying the Bondesson composition with Trujillo’s fibronectin-PEG-maleimide, as discussed above, the maleimide would act as a blocking group to result in a scaffold that has suspended modified ECM proteins. It would have been obvious to one of ordinary skill in the art to incorporate these ECM proteins, along with the Matrigel-like gelatin structure in GelMA, to highly sequester GFs without hydrogel-attachment hinderance to garner increased early cell activity, as seen in Trujillo and Lin.
Regarding claim 33, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). Bondesson further teaches the inclusion of a cell line of human origin, a growth factor, and proteins such as cytokines in the printed composition (pg. 1, [0009], (e)).
Regarding claim 34, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). Bondesson further teaches the use of LAP as a photoinitiator (pg. 1, [0009], (e)).
Regarding claim 35, Bondesson, Trujillo, and Lin teach the composition obvious to one of ordinary skill in the art discussed in (12 – 16). Trujillo further teaches the formation of hydrogel in PBS, where the biocompatible polymer is dissolved in PBS prior to gelation.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Trujillo-Muñoz (Ph.D. Thesis, University of Glasgow, 2019) teaches engineered fibronectin-based hydrogels with thiolating and photocuring crosslinking in addition to hydrogels with suspended native fibronectin.
Barros et al. (Biomaterials 252 (2020) 120104. https://doi.org/10.1016/j.biomaterials.2020.120104) discloses engineered hydrogels with attached laminin.
Belair et al. (Chem Commun (Camb). 2014 December 25; 50(99): 15651 -15668. doi:10.1039/c4cc04317k.) discloses sequestration techniques in biomaterials.
Gobaa and Lutolf (US Pat. No. US 10379107 B2) discloses a microarray partially crosslinked hydrogel with biomolecules, including ECM proteins.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARMAN M. FARAZDAGHI whose telephone number is (571)270-5813. The examiner can normally be reached Monday - Friday, Monday - Thursday, 8:30 am - 5:00 pm.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Jones can be reached at (571) 270-7733. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARMAN M. FARAZDAGHI/Examiner, Art Unit 1762
/ROBERT S JONES JR/Supervisory Patent Examiner, Art Unit 1762
Prosecution Insights