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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/11/2026 has been entered.
Status of Claims
Claims 1 and 3-10 are pending.
Claims 1 and 7 are currently amended.
Claims 11-12 have been cancelled.
Applicant previously elected Group I, drawn to claims 1-6, without traverse in the reply filed on 07/22/2025. Claims 7-10 are withdrawn from consideration as being drawn to a non-elected invention.
Claims 1 and 3-6 are examined on the merits herein.
Withdrawn Rejections
The rejection of 1 and 3-6 under 35 U.S.C. 102(a)(1) as being anticipated by Hwang (Biomaterials, 2007, 28(28): 4039-4046) is withdrawn in light of the amendments to claim 1.
The provisional rejection of claims 1 and 3-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/728,033 is withdrawn because Applicant filed a Terminal Disclaimer on 05/11/2026, which was approved on 05/11/2026.
The cancellation of claim 11 renders any rejections thereof moot.
Claim Interpretation
Claim 1 recites the limitation “aggregated particles.” Absent a definition in the specification, the broadest reasonable interpretation of “aggregated particles,” which is “two smaller particles merging together to form a larger particle” (Taylor & Francis, “Particle Aggregation,” provided in the Office Action mailed 02/09/2026), is used for the purpose of examination.
Claim 1 recites the limitation “wherein the aggregated particles are obtained by treating, on the non-porous surface, a cell culture coating composition prepared by mixing (i) an active solution comprising a carbodiimide-based coupling agent and N-hydroxysulfosuccinimide (Sulfo-NHS), and (ii) the fusion protein” (lines 7-10), which is a product-by-process limitation. This limitation is given patentable weight based on the Declaration under 37 CFR 1.132 filed 11/11/2025, which shows that a cell culture coating solution comprising an active solution comprising a carbodiimide-based coupling agent and Sulfo-NHS results in a different coating layer (i.e., results in a coating surface formed by aggregated particles, as shown in Supplementary Table 1, Example 1) compared to a cell culture coating solution that does not comprise a carbodiimide-based coupling agent and Sulfo-NHS (i.e., results in a smooth coating surface without aggregated particles, as shown in Supplementary Table 1, Comparative Example 5).
Claim Rejections - 35 USC § 112(b)
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.
Claims 1 and 3-6 are 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 1 recites the phrase “wherein the aggregated particles are obtained by treating, on the non-porous surface, a cell culture coating composition prepared by mixing (i) an active solution comprising a carbodiimide-based coupling agent and N-hydroxysulfosuccinimide (Sulfo-NHS), and (ii) the fusion protein.” It is unclear what is meant by “treating a cell culture coating composition.” For the purpose of examination, this phrase is interpreted as “wherein the aggregated particles are obtained by treatingwith a cell culture coating composition, wherein the cell culture coating composition is prepared by mixing (i) an active solution comprising a carbodiimide-based coupling agent and N-hydroxysulfosuccinimide (Sulfo-NHS), and (ii) the fusion protein.”
Claims 3-6 are included in the rejection because they depend from claim 1.
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 and 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Kuo (Topics in Catalysis, 2018, 61: 1139-1147), in view of Hwang 1 (Biomaterials, 2007, 28(28): 4039-4046) and ThermoFisher (“Amine-Reactive Crosslinker Chemistry”, 2019, Accessed via Wayback Machine), as evidenced by Hwang 2 (Biomaterials, 2007, 28(24): 3560-3568) and Kitamura (Journal of Polymer Science Part A: Polymer Chemistry, 1999, 37(6): 729-736).
Regarding claim 1: Kuo teaches a stem cell culture system comprising surface-functionalized polymeric micropillars, wherein the micropillars are made from polydimethylsiloxane (reads on a substrate having a non-porous surface) and are modified with vitronectin-derived peptides (reads on a functional peptide that promotes one or more of adhesion, migration, proliferation, and differentiation of a cell) and are used as substrates to maintain both human embryonic stem cells and induced pluripotent stem cells for up to 3 months without differentiation (Abstract; Section 2.1; Fig 1).
Kuo teaches coupling a layer of peptides to the surface of the micropillars (Sections 2.2, 3.2; Fig 4a). The micropillars were modified with amino-terminated peptides through a two-step process: first, the surfaces of the micropillars were grafted with carboxylic acid functional groups. This first step comprised immersing ultraviolet-curable adhesives into a 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling reaction to convert the carboxyl groups on the micropillar surface. In the second step, peptides were covalently immobilized on the polymeric micropillars through an EDC/NHS-mediated reaction, wherein vinyl-NHS functional groups on the micropillars were coupled to the amine-containing peptides (reads on mixing (i) an active solution comprising a carbodiimide-based coupling agent and N-hydroxysulfosuccinimide (Sulfo-NHS), and (ii) the fusion protein) (Sections 2.2, 3.2; Fig 4a).
Kuo does not teach a fusion protein in which a functional peptide is bound to a mussel adhesive protein. Kuo is also silent regarding the appearance (i.e., absence or presence of aggregated particles) of the cell culture coating layer.
Hwang 1 teaches fp-151-RGD, a recombinant fusion protein suitable for use as a cell-adhesion materials in cell culture, comprising 1) the recombinant mussel adhesive protein (MAP) fp-151, and 2) the GRGDSP peptide, which is attached to the C-terminus of MAP fp-151 (Abstract). The GRGDSP peptide comprises the RGD sequence, which is a cell-adhesion-recognition motif and is the ligand for integrin-mediated cell adhesion, which involves a cascade of four overlapped reactions: cell attachment, cell spreading, actin-skeleton formation, and focal-adhesion formation (Introduction, para 3). Hwang 1 teaches a cell culture substrate comprising polystyrene 24-well culture plates coated with fp-151-RGD (Section 2.7). Surfaces coated with tyrosinase-modified fp-151-RGD formed porous structures (Section 3.1, para 2; Section 3.2; Fig 2E), which comprises aggregated particles. HeLa, 293T, and CHO cultured on surfaces coated with fp-151-RGD showed superior cell spreading and attached morphology compared with the same cells cultured on other materials (Section 3.3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cell culture substrate of Kuo by using fp-151-RGD, as taught in Hwang 1, as the peptide. One of ordinary skill in the art would have been motivated to make this modification because Hwang 1 teaches that fp-151-RGD, when used as a coating surface for cell culture, promotes cell spreading and adhesion. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Hwang 1 teaches that fp-151-RGD can be used as a coating for cell culture.
Kuo teaches the use of N-hydroxysuccinimide (NHS) in the coupling reaction. Kuo, in view of Hwang 1, does not teach the use of N-hydroxysulfosuccinimide (Sulfo-NHS).
ThremoFisher teaches that Sulfo-NHS esters are identical to NHS esters except that they contain a sulfonate (–SO3) group on the N-hydroxysuccinimide ring, which has no effect on the reaction chemistry (p 3, para 1).
Given the teachings of ThermoFisher, there was a reasonable expectation that Sulfo-NHS and NHS would work equivalently in a coupling reaction with EDC. Therefore, it would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention to have substituted NHS with Sulfo-NHS in the coupling reaction of Kuo with predictable results. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Regarding claim 3: Following the discussion of claim 1, Hwang 1 teaches a cell culture substrate comprising polystyrene 24-well culture plates coated with fp-151-RGD (Section 2.7).
Regarding claims 5-6: Following the discussion of claim 1, Hwang 1 teaches that fp-151-RGD comprises the sequence GRGDSP at the C-terminus of fp-151 (Abstract; Fig 1A) (claim 5). The GRGDSP peptide of fp-151-RGD comprises the amino acid sequence RGD, which is the sequence set forth in SEQ ID NO: 18 (claim 6).
Regarding claim 4: Following the discussion of claim 1, Hwang 1 teaches that fp-151, a fusion protein with six type 1 (fp-1) decapeptide repeats at each type 5 (fp-5) terminus (Abstract; Fig 1A), is described in Hwang 2 (cited as reference 15 in Introduction, para 2).
Hwang 2 shows that in the construction of fp-151, a gene for six fp-1 decapeptide rerepeats was synthesized according to the method of Kitamura (Section 2.1).
Kitamura shows that each fp-1 decapeptide has a sequence AKPSYPPTYK (Abstract), which is identical to the amino acid sequence set forth in SEQ ID NO: 1. Moreover, the six fp-1 decapeptide repeat is identical to the sequence set forth in SEQ ID NO: 3.
Response to Arguments
Applicant’s arguments and amendments dated 05/11/2026 have been fully considered but are moot in part and not persuasive in part due to the new grounds of rejection necessitated by applicant’s amendments. To the extent that the arguments are pertinent to the current grounds of rejection they are responded to below.
Applicant argues: As discussed in paragraph 8 of the Seo Declaration filed November 11, 2025, Kuo discloses a process in which EDC/NHS is first applied to a micropillar surface and then washed away with PBS before peptide treatment. Kuo fails to disclose or suggest "mixing (i) an active solution comprising a carbodiimide-based coupling agent and N-hydroxysulfosuccinimide (Sulfo-NHS) and (ii) the fusion protein," as recited in amended claim 1.
In response: Applicant’s arguments have been fully considered, but are not persuasive. First, Kuo teaches a process in which EDC/NHS is first applied to a micropillar surface, followed by peptide conjugation to the micropillar surface, as asserted by Applicant (Section 2.2 of Kuo). However, Kuo does not teach “washing [the EDC/NHS] away with PBS before peptide treatment,” as asserted by Applicant. Rather, Kuo teaches that “The surfaces of the micropillars were then cleaned twice with ethanol and a PBS solution after peptide conjugation” (Section 2.2).
Furthermore, the limitation “mixing,” as recited in claim 1, merely requires that (i) an active solution comprising a carbodiimide-based coupling agent and Sulfo-NHS and (ii) the fusion protein are combined. The limitation “mixing” does not place a temporal constraint on this process, or place a constraint on how the process is carried out. Therefore, conjugating a peptide to a micropillar substrate whose surface is modified with the active solution of (i), as taught in Kuo, reads on the limitation recited in the last three lines of claim 1.
Conclusion
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/RISA TAKENAKA/Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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