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 reply dated 08/14/2026 has been received.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 05/11/2026 is acknowledged.
Claims 12-15,22-25,30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected withdrawn, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/11/2026.
Applicant does request that the restriction requirement be reconsidered. Applicant is reminded, where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
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.
The rejection of claims 1-10 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 is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claim(s) 1-4,6-9 under 35 U.S.C. 102a1 as being anticipated by Mosquera (medRxiv preprint doi: https://doi.org/10.1101/2020.05.17.20104349; posted May 20, 2020; IDS) is withdrawn. Mosquera taught prostate cancer cells on the scaffold, not breast cancer cells as is now recited.
The rejection of claim(s) 1-3 and 9 under 35 U.S.C. 102a1 and a2 as being anticipated by US 20180258403 (Ecole; IDS) is withdrawn. Ecole does not teach use of a bis-cysteine crosslinking peptide
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.
1A) The rejection of claim(s) 1-3 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable Mosquera (medRxiv preprint doi: https://doi.org/10.1101/2020.05.17.20104349; posted May 20, 2020; IDS) in view of US2020/0078493 (GA Tech; IDS) is withdrawn. Neither reference taught breast cancer cells. A new rejection is set forth immediately below based on similar grounds.
1A’) Claim(s) 1-3,5 and 7-9 is/are rejected under 35 U.S.C. 103 as being unpatentable Mosquera (medRxiv preprint doi: https://doi.org/10.1101/2020.05.17.20104349; posted May 20, 2020; IDS) in view of Enemchukwu (2016, J. Cell Biol. Vol. 212, 113-124).
Claim 1 is drawn to a cell matrix scaffold comprising a polyethylene glycol (PEG) hydrogel conjugated to a cell adhesive peptide, and a bis-cysteine crosslinking peptide thatcomprises a population of breast cancer cells.
Mosquera taught a PEG-4MAL (claim 9) hydrogel scaffold comprising 1) a cell adhesive peptide, GRGDSPC (SEQ ID NO:1, claims 2-4), a crosslinking peptide GCRDVPMSMRGGDRCG (SEQ ID NO:3, claims 6-8). Mosquera teaches the 3D hydrogels for growth of prostate tumor cells (para 1).
Mosquera fails to teach culture of breast cancer cells on the scaffold.
However, Enemchukwu taught PEG-4MAL PEG hydrogels that are crosslinked with bis-cysteine crosslinking peptides and RGD cell adhesive peptides (page 118m, col. 1) for culture of a variety of cells (page 114, Col. 1). Enemchukwu taught these hydrogels were tunable (Figure 1) to meet the ECM characteristics of different cell types. Figure 2 supports that polymer density regulates epithelial morphogenesis. Page 118 and Figure 4 discusses variation of RGD peptide density. Enemchukwu states, “This study establishes a modular synthetic ECM-mimetic hydrogel platform with controlled presentation of cell-adhesive ligands, tunable mechanical properties, and protease-dependent degradation that can be precisely engineered to study the contributions of ECM biophysical and biochemical properties on the epithelial morphogenetic program.” And, “We expect that this biomaterial platform will find widespread adoption in developmental cell and tumor biology fields to study ECM-regulated morphogenetic processes” (Discussion).
It would have been obvious at the time of filing to tune the PEG-4MAL macromer hydrogel scaffold of Mosquera to grow breast tumor cells in place of prostate cancer cells to arrive at the invention as claimed. One would have been motivated to make such a substitution to generate in vitro breast tumors for study of EMT as well as for screening for treatments ad Emenuchukwu taught “We expect that this biomaterial platform will find widespread adoption in developmental cell and tumor biology fields to study ECM-regulated morphogenetic processes” (Discussion). One would have had a reasonable expectation of success in making the combination as Emenchukwu taught that the same scaffoled (PEG-4MAL macromer hydrogel scaffold comprising cell-adhesive RGD peptides crosslinked with bis-cysteine peptides) was tunable by altering the ratio of cell-adhesive and crosslinking peptides in combination with PEG densities to meet the ECM needs of various cells types
1B’) Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable Mosquera (medRxiv preprint doi: https://doi.org/10.1101/2020.05.17.20104349; posted May 20, 2020; IDS) in view of Enemchuwku (2016, J. Cell Biol. Vol. 212, 113-124) as set forth for claims 1-3 in view of US2020/0078493 (GA Tech; IDS).
Mosquera and Enemchukwu meet the limitations of claims 1-3 as set forth above.
With regard to claim, 5, neither Mosquera mor Enemchukwu teach the cell adhesive peptide of SEQ ID NO:2, GRDGSPC.
GA Tech, however, teaches the GRDGSPC as an adhesive peptide (see Abstract, para 71) on a PEG-4MAL. Notably, GA Tech teaches mixing the cell adhesive peptide with PEG-4MAL at a 2:1 PEG:ligand ratio to generate a functionalized PEG-4MAL precursor. GA Tech teaches making hydrogels with the adhesive peptide (GRDGSPC /SEQ ID NO:2) functionalized PEG-4MAL macromer, cells and crosslinking peptide (para 56).
It would have been obvious at the time of filing to substitute the RDG peptide of GA Tech with the cell adhesive peptide of Mosquera to arrive at the claimed scaffold wherein the cell adhesive peptide is SEQ ID NO:2. The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. ___, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In the present situation, rationales A, B and E are applicable. The substitution of any of the RGD-containing sequence of Mosquera with that of Garcia (SEQ ID NO:2) represents combining prior known compounds to yield predictable results, substitution for one known element for another, and choosing from a finite number of identified, predictable results. The teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
2A) The rejection of claim(s) 1-3,4,7-9 under 35 U.S.C. 103 as being unpatentable over US 20180258403 (Ecole; IDS) in view of Phelps (Adv Mater. 2012 January 3; 24(1): 64–2. doi:10.1002/adma.201103574; IDS) and Cruz-Acuna (Nat Protoc. 2018 September ; 13(9): 2102–2119. doi:10.1038/s41596-018-0036-3; IDS). Phelps and Cruz-Acuna provide some dependent limitations but do not directly relate to tumors or breast/mammary cancer.
2A’) Claim(s) 1-3,4,7-9 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180258403 (Ecole; IDS) in view of Enemchuwku (2016, J. Cell Biol. Vol. 212, 113-124) and further in view of Phelps (Adv Mater. 2012 January 3; 24(1): 64–2. doi:10.1002/adma.201103574; IDS) and Cruz-Acuna (Nat Protoc. 2018 September ; 13(9): 2102–2119. doi:10.1038/s41596-018-0036-3; IDS).
Ecole teaches 3D hydrogels for growth of tumor cells (para 1). Ecole teaches that the hydrogels are bioactive hydrogels containing a bio-adhesive molecule that can be fibronectin derived RGD (claims 2-3). With regard to crosslinking, at para 70 Ecole taches multi-arm PEG-based polymers can be crosslinked with cell-compatible reactions (para 53) and at para 97 discusses use of transglutaminase as an example to crosslink with glutamine and lysine bearing substrates. Para 71 teaches that the PEG can be a 4-arm PEG end functionalized with a maleimide (para 73, claim 9). With regard to the newly recited population of breast cancer cells, Ecole teaches the scaffolds can be used for cells from prostate or mammary (breast) tumor. Ecole teaches a multi-arm PEG functionalized with a maleimide and an RGD peptide as a cell-adhesive peptide as a hydrogel for growth of tumor cells (cancer). Ecole teaches several RGD containing peptides (e.g. RGD, RGDS, RGDSP, RGDSPK, RGDTP, RGDSPASSKP; para 77) but does not teach SEQ ID NO:1, GRGDSPC, use of VPM as a bis-cysteine crosslinking peptide that has the sequence set forth by SEQ ID NO:3 (GCRDVPMSMRGGDRCG).
However, Enemchukwu taught PEG-4MAL (claim 9) PEG hydrogels that are crosslinked with bis-cysteine crosslinking peptides and RGD cell adhesive peptides (page 118m, col. 1) for culture of a variety of cells (page 114, Col. 1). Enemchukwu taught these hydrogels were tunable (Figure 1) to meet the ECM characteristics of different cell types. Figure 2 supports that polymer density regulates epithelial morphogenesis. Page 118 and Figure 4 discusses variation of RGD peptide density. Enemchukwu states, “This study establishes a modular synthetic ECM-mimetic hydrogel platform with controlled presentation of cell-adhesive ligands, tunable mechanical properties, and protease-dependent degradation that can be precisely engineered to study the contributions of ECM biophysical and biochemical properties on the epithelial morphogenetic program.” And, “We expect that this biomaterial platform will find widespread adoption in developmental cell and tumor biology fields to study ECM-regulated morphogenetic processes” (Discussion). Enemchukwu teaches a PEG-4MAL (claim 9) with an adhesive RGD containing sequence of SEQ ID NO:1 (GRGDSPC; claim 4) as an adhesive ligand. Enemchukwu teaches bis-cysteine crosslinking peptides but doesn’t teach that specifically recited in claim 8.
Phelps also teaches a PEG-4MAL (claim 9) with an adhesive RGD containing sequence of SEQ ID NO:1 (GRGDSPC) as an adhesive ligand for cell growth and a crosslinking bis-cysteine VPM peptide having the sequence set forth by SEQ ID NO:3 (claims 7-8; GCRDVPMSMRGGDRCG).
Like Enemchukwu, Cruz-Acuna discusses the tunability of PEG-4MAL platform to adapt to culture of a variety of cells and organoids (page 3). Cruz-Acuna teaches polymer density, maleimide and crosslinking peptide ratio as well as the nature of the crosslinking peptide (fast vs slow degrading) as variables that can be used to tune the scaffold to accommodate specific cells and the scaffold of Cruz-Acuna comprises PEG-4MAL, SEQ ID NO1 as an adhesive peptide for cell culture (page 6). Cruz-Acuna teaches further variations of the biophysical and biochemical matrix properties can be explored if an initial hydrogel formulation does not support the viability and growth.
It would have been obvious at the time of filing to substitute the RGD peptide and VPM peptide of Phelps for any of those of Ecole and Enemchukwu to arrive at the claimed scaffold wherein the cell adhesive peptide is SEQ ID NO:1 and the crosslinking polypeptide of SEQ ID NO3 to culture the mammary cancer cells of Ecole. One would have been motivated to make such a combination/substitution of known species given the teachings of Cruz-Acuna. One would have had a reasonable expectation of success in making the combination but it was a matter of routine experimentation to substitute the claimed groups and vary the ratios to arrive at a desirable scaffold for any type of cell.
2B) The rejection of claim(s) 1-3 and 5 remain rejected under 35 U.S.C. 103 as being unpatentable over US 20180258403 (Ecole) in view of US2020/0078493 (GA Tech) as GA Tech did not teach the bis-cysteine crosslinking peptide.
2B’) Claim(s) 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180258403 (Ecole) US 20180258403 (Ecole; IDS) in view of Enemchuwku (2016, J. Cell Biol. Vol. 212, 113-124) and further in view of Phelps (Adv Mater. 2012 January 3; 24(1): 64–2. doi:10.1002/adma.201103574; IDS) and Cruz-Acuna (Nat Protoc. 2018 September ; 13(9): 2102–2119. doi:10.1038/s41596-018-0036-3; IDS) as set forth above for claims 1-3,4,7-9 further in view of US2020/0078493 (GA Tech).
Ecole meets the limitations of claim 1 as set forth above. Ecole teaches a multi-arm PEG functionalized with a maleimide and an RGD peptide as a cell-adhesive peptide as a hydrogel for growth of mammary tumor cells (breast cancer). Ecole teaches several RGD containing peptides (e.g. RGD, RGDS, RGDSP, RGDSPK, RGDTP, RGDSPASSKP; para 77) but does not teach SEQ ID NO:1, GRGDSPC. GA Tech, however, teaches the GRDGSPC as an adhesive peptide (see Abstract, para 71) on a PEG-4MAL. Notably, GA Tech teaches mixing the cell adhesive peptide with PEG-4MAL at a 2:1 PEG:ligand ratio to generate a functionalized PEG-4MAL precursor. GA Tech teaches making hydrogels with the adhesive peptide (GRDGSPC /SEQ ID NO:2) functionalized PEG-4MAL macromer, cells and crosslinking peptide (para 56). GA Tech teaches use of a bis-cysteine crosslinking peptide (claim 6) GPQ-W.
It would have been obvious at the time of filing to substitute the RDG peptide and the bis-cysteine crosslinking peptide of GA Tech for any of the cell adhesive peptides and the bio-compatible crosslinking peptides of Ecole, especially given the teachings of Enemchukwu and Cruz-Acuna regarding the tunability of the PEG-4MAL scaffolds, to arrive at the claimed scaffold wherein the cell adhesive peptide is SEQ ID NO:2 and the crosslinking peptide is a bis-cysteine crosslinking peptide. The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. ___, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In the present situation, rationales A, B and E are applicable. The substitution of any of the RGD-containing sequences of Ecole with that of GA Tech (SEQ ID NO:2) as well as the bis-cysteine peptide for a bio-compatible crosslinking peptide represents combining prior known compounds to yield predictable results, substitution for one known element for another, and choosing from a finite number of identified, predictable results. The teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
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 VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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, Peter Paras can be reached at 571-272-4517. 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.
VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights