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 .
Election/Restrictions
Applicant previously elected Group I, drawn to claims 1-6, without traverse in the reply filed on 07/22/2025.
Claims 1, 3-6, and 11 are examined herein. Claim 11 is new.
Claims 7-10 and 12 are withdrawn from consideration as being drawn to a non-elected invention.
Withdrawn Claim Rejections
The rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn in light of the amendment to the claim to delete the limitation “for cell culture” in line 5.
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1-6 of copending Application No. 17/788,886 in view of Scholz (Thermo Fisher Scientific Technical Bulletin, 2010) is withdrawn because Applicant filed a Terminal Disclaimer on 11/11/2025, which was approved on 11/11/2025.
The cancellation of claim 2 renders any rejections thereof moot.
Claim Interpretation
Amended claim 1 and new claim 11 recite the limitation “aggregated particles.” This limitation is not defined in the specification, and therefore, the broadest reasonable interpretation of “aggregated particles,” which is “two smaller particles merging together to form a larger particle” (Taylor & Francis, “Particle Aggregation”), is used for the purpose of examination.
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.
Claims 1 and 3-6 remain rejected, and new claim 11 is rejected, under 35 U.S.C. 102(a)(1) as being anticipated by Hwang (Biomaterials, 2007, 28(28): 4039-4046; cited in IDS filed 03/13/2024), 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).
Hwang discloses fp-151-RGD, a fusion protein comprising 1) the recombinant mussel adhesive protein fp-151, and 2) the GRGDSP peptide, an RGD peptide at the cell attachment site of fibronectin, attached to the C-terminus of MAP fp-151 (Abstract; claims 1, 5). Hwang discloses that fp-151 is a fusion protein with six type 1 (fp-1) decapeptide repeats at each type 5 (fp-5) terminus (Abstract), as disclosed in Hwang 2 (cited as reference 15 on p 4040, 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 (claim 4, a protein to which one or more amino acid sequences selected from the group are linked). Moreover, the six fp-1 decapeptide repeat is identical to the sequence set forth in SEQ ID NO: 3 (claim 4). 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, a peptide to which one or more amino acid sequences selected from the group are linked).
Hwang discloses a cell culture substrate comprising untreated polystyrene 24-well culture plates coated with fp-151-RGD (Section 2.7; claims 1, 3, 5). Hwang discloses that surfaces coated with fp-151-RGD display a pattern of aggregated particles having a granular shape, as observed with atomic force microscopy (AFM) (Section 3.2; Fig 2D, 2E) (claims 1, 11). Hwang further discloses culturing Wildtype HeLa, 293T, and Chinese hamster ovary cells on the coated wells and performing cell spreading (reads on migration), adhesion, and proliferation assays (Section 2.8; claim 1). Hwang discloses that fp-151-RGD showed superior cell spreading and attached morphology (reads on adhesion) for all assayed cell types compared with other materials tested (Section 3.3; claim 1). Hwang further discloses that fp-151-RGD induced the formation of an actin cytoskeleton, resulting in an increase in focal adhesions, which suggests that RGD-motif-mediated adhesion by fp-151-RGD promotes cell proliferation (Section 3.3; 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) 6 remains rejected under 35 U.S.C. 103 as being unpatentable over Hwang (Biomaterials, 2007, 28(28): 4039-4046; cited in IDS filed 03/13/2024), 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), in view of Kuo (Topics in Catalysis, 2018, 61: 1139-1147).
Hwang, as evidenced by Hwang 2 and Kitamura, anticipates claim 1.
Regarding claim 6: Hwang does not teach the cell culture substrate according to claim 1, wherein the functional peptide has the sequence set forth in SEQ ID NO: 15.
Kuo teaches a stem cell culture system, wherein micropillars modified with vitronectin-derived peptides are used as substrates to maintain human embryonic stem cells and induced pluripotent stem cells (Abstract). The peptides used in the experiment include a peptide derived from vitronectin (Ac-KGGPQVTRGDVFTMP), and a short peptide containing RGD residues (GRGDSPK) (Section 2.2). The short peptide GRGDSPK has an additional lysine compared to the RGD peptide taught in Hwang (GRGDSP). The vitronectin-derived peptide taught in Kuo is a 100% match to the amino acid sequence set forth in SEQ ID NO: 15 of the instant application (see alignment below).
Query Match 100.0%; Score 82; DB 1; Length 15;
Best Local Similarity 100.0%;
Qy 1 KGGPQVTRGDVFTMP 15
|||||||||||||||
Db 1 KGGPQVTRGDVFTMP 15
Kuo teaches that human iPS cells cultured on micropillars modified with vitronectin-derived peptides maintained their undifferentiated state, compared to human iPS cells cultured on micropillars modified with short peptides comprising RGD residues (Section 3.3, para 3). Kuo teaches that these results are consistent with previous observations, wherein surface modification using vitronectin-derived peptides improved human embryonic stem cell adhesion and promoted long-term cell proliferation in vitro (Section 3.3, para 3).
It would have been prima facie obvious to 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 Hwang by substituting the short peptide GRGDSPK with the vitronectin-derived peptide KGGPQVTRGDVFTMP, which is identical to the sequence set forth in SEQ ID NO: 15, as taught in Kuo. One of ordinary skill in the art would have been motivated to make this modification because Kuo teaches that substrates modified with the vitronectin-derived peptide KGGPQVTRGDVFTMP allows iPS cells to be maintained in their undifferentiated state, compared to substrates coated with shorter peptides comprising an RGD sequence. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Kuo teaches that the vitronectin-derived peptide KGGPQVTRGDVFTMP can be used to modify cell culture substrates.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-6 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of copending Application No. 18/728,033 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a cell culture scaffold (reads on substrate) comprising a cell culture coating layer covering at least a portion of the surface of the scaffold, and a fusion polypeptide (reads on fusion protein) comprising a peptide for cell culture and a peptide for adhesion (copending claim 1; reads on instant claim 1), wherein the scaffold is a non-porous scaffold selected from the group of materials recited in instant claim 3 (copending claim 2; reads on instant claims 1, 3), the adhesion peptide is derived from a mussel adhesive protein (copending claim 4; reads on instant claim 1), and the peptide for cell culture promotes one or more of cell adhesion, movement, proliferation, and differentiation (copending claim 3; reads on instant claim 1). Copending claim 5 reads on instant claim 4 (e.g., SEQ ID NO: 1 of the copending and instant applications are identical), and copending claim 6 reads on instant claims 5 and 6 (e.g., SEQ ID NO: 16 of the copending application is identical to SEQ ID NO: 17 of the instant application, which comprises an RGD sequence).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Declaration submitted under 37 C.F.R. 1.132
The declaration under 37 CFR 1.132 filed 11/11/2025 is insufficient to overcome the rejection of claims 1 and 3-6 based upon 35 U.S.C. 102 and 35 U.S.C. 103 as set forth in the last Office action. The declaration comprises an additional example (Comparative Example 5), which demonstrates that the use of an active solution, comprising carbodiimide coupling agent and a reactive agent, in addition to fusion protein results in a cell culture coating layer formed by aggregated particles, whereas the use of fusion protein alone without the active solution results in a cell culture coating layer with a smooth coating surface (p 4, Supplementary Table 1: Example 1 and Additional Comparative Example 5). Claim 1, which is drawn to the product of a cell culture substrate, does not require an active solution comprising carbodiimide coupling agent and a reactive agent in the final product, but merely requires that the cell culture substrate comprise a cell culture coating layer comprising aggregated particles formed of a fusion protein. The culture coating layer disclosed in Hwang does comprise aggregated particles formed of a fusion protein, as set forth above in the rejection under 35 U.S.C. 102.
Furthermore, although the Declaration states that “The cell culture coating layer of claim 1 comprises aggregated particles formed of a fusion protein in which a functional peptide is bound to a mussel adhesive protein. These shape characteristics of the cell culture coating layer are uniquely generated due to the manufacturing method of the present disclosure, e.g., as recited in Claim 7” (p 2, para 4), instant claim 1 is drawn to a product, not a manufacturing method. Therefore, the limitations in the steps of claim 7 (e.g., “an active solution”) are not required in the product of claim 1.
Rejection Under 35 U.S.C. § 102
Applicant argues: In the declaration submitted herewith, ("Seo Declaration"), inventor Dong Sik Seo discusses the morphological characteristics of the claimed invention. Per paragraph 5 of the Seo Declaration, a specific morphology of the cell culture coating layer, namely aggregated particles, is
needed to achieve the benefits of the claimed invention. This morphology and the benefits arising therefrom are not disclosed by Hwang. Accordingly, Applicant respectfully submits that claim 1 is not anticipated by Hwang for the following reasons.
First, Hwang does not disclose "a cell culture coating layer comprises aggregated particles". To anticipate a claim, a reference must disclose all of the limitations of the claim," arranged or combined in the same way as in the claim," or such that "a person of skill in the art, reading the reference, would 'at once envisage' the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015); Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008); MPEP §2131. The Office failed to cite, and Hwang fails to disclose or suggest, the "the cell culture coating layer comprises aggregated particles," as recited in claim 1. Thus, claim 1 is not
anticipated by Hwang for at least this reason.
In response: Applicant’s arguments have been fully considered, but are not found persuasive. As set forth above in the rejection under 35 U.S.C. 102, Hwang does disclose a cell culture coating layer comprising aggregated particles (Section 3.2; Fig 2D, 2E).
Applicant further argues: Second, a person of ordinary skill in the art following the disclosure of Hwang would not arrive at a cell culture coating layer that comprises aggregated particles. To further demonstrate this point, Applicant tested an additional comparative example (Comparative Example 5) as set forth in paragraph 6 of the Seo Declaration. Thus, a person of ordinary skill in the art following the surface coating method disclosed by Hwang (Section 2.7) would not arrive at the claimed cell culture coating layer that comprises aggregated particles.
In response: Applicant’s arguments have been fully considered, but are not found persuasive. Comparative Example 5 shows that a coating composition prepared in the absence of a coupling agent and reactive agent does not form aggregated particles (para 5 of Declaration; Supplementary Table 1). However, Hwang does disclose a cell culture coating layer comprising aggregated particles (Section 3.2; Fig 2D, 2E). In the absence of a definition for the limitation “aggregated particles,” the broadest reasonable interpretation of the phrase is “two smaller particles merging together to form a larger particle” (see Claim Interpretation). Therefore, the cell culture coating layer as claimed in claim 1 is not patentably distinct from the cell culture coating layer disclosed in Hwang.
Applicant further argues: Third, the cell culture substrate of Hwang would not have the technical advantages of the instantly claimed cell culture substrate, citing paragraph 7 [Examiner believes Applicant meant to cite paragraph 6] of the Seo Declaration. Accordingly, Hwang fails to disclose or suggest the claimed cell culture coating composition that comprises aggregated particles and fails to disclose or suggest a method of preparing the claimed cell culture coating composition.
In response: Applicant’s arguments have been fully considered, but are not found persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., improved storage stability at room temperature when a substrate is provided with the cell culture coating layer of claim 1, which is manufactured according to the method of claim 7; see lines 1-3 of paragraph 6 of the Seo Declaration) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Although amended claim 7 is drawn to “A method of manufacturing the cell culture substrate of claim 1,” instant claim 1 does not require that the claimed cell culture substrate be made according to the steps in the method of claim 7. Therefore, the limitations in the steps of claim 7 (e.g., “an active solution containing a carbodiimide-based coupling agent and a reactive agent comprising N-hydroxysulfosuccinimide (Sulfo-NHS)” in step 1) are not required in the product of claim 1.
Rejection Under 35 U.S.C. § 103
Applicant argues: Applicant's above arguments with respect to the rejection under 35 U.S.C. § 102 are incorporated here. As discussed above, Hwang fails to disclose or suggest the cell culture coating layer of claim 1. Kuo also fails to disclose or suggest a cell culture coating layer that comprises aggregated particles. Moreover, as discussed in paragraph 8 of the Seo Declaration, Kuo fails to disclose or suggest a method that would result in a cell culture coating layer that comprises aggregated particles.
In response: Applicant’s arguments have been fully considered, but are not found persuasive. As discussed above, Hwang does disclose a cell culture coating layer that reads on the cell culture substrate of claim 1, including the limitation of “aggregated particles.” Kuo is not relied upon in the 35 U.S.C. § 103 rejection for the limitation of “aggregated particles.”
Provisional Double Patenting Rejection over claims 1-6 of copending Application No. 18/728,033
Applicant argues: US 18/728,033 has an effective filing date of January 11, 2023, which is after the December 27, 2020 effective filing date of the present application. Under MPEP 804(1)(B)(l )(b )(i), the provisional rejection based on 18/728,033, which has a later patent term filing date should be withdrawn upon a finding of allowability of the claims of this earlier filed application.
In response: Applicant’s arguments have been fully considered, but are not found persuasive because there are outstanding rejections in the instant application, as set forth above.
Conclusion
THIS ACTION IS MADE FINAL. 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 Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632