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
This application claims benefit of priority to Provisional Application 63/126,245 filed 12/16/2020 and is also a 371 of PCT/KR2021/019159 filed 12/16/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 05/18/2023, 03/05/2024, 06/24/2024 and 10/29/2024 have been acknowledged and considered.
Drawings
The Drawings filed 05/18/2023 are accepted by the Examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-17, in the reply filed on 03/02/2026 is acknowledged.
Regarding the species elections, Applicant’s election without traverse of fibronectin domain III, SEQ ID NO: 12, transforming growth factor β (TGF-β), SEQ ID NO: 50 (RGD), integrin avβ6 and SEQ ID NO: 59 in the reply filed on 03/02/2026 is acknowledged.
Claim Status
As stated above, Applicant elected SEQ ID NO: 50 (RGD) as the specific integrin binding motif. Claim 9, the claim drawn to a specific integrin binding motif, does not recite SEQ ID NO: 50. Therefore, claim 9 is withdrawn as it is not encompassed by the election of species. Additionally, Applicant elected SEQ ID NO: 59 as the specific recombinant mussel adhesive protein. Claim 13, the claim drawn to a specific recombinant mussel adhesive protein does not recite SEQ ID NO: 59. Therefore, claim 13 is withdrawn as it is not encompassed by the election of species.
Claims 1-19 are currently pending.
Claims 4-7, 9, 11, 13 and 18-19 are withdrawn as they are not encompassed by the elected group or the elected species.
Claims 1-3, 8, 10, 12, 14-17 are under examination.
Claim Objections
Claim 16 is objected to because of the following informalities: Claim 16 recites “the integrin binding motif and the heparin binding motif is connected” in lines 1-3. The use of ‘is connected’ is grammatically incorrect. The claim should read “the integrin binding motif and the heparin binding motif are connected.” Appropriate correction is required.
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.
Claims 1-2, 8, 10 and 12 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Kim et al. (US 20160355780 A1, 12/08/2016) (IDS Reference of 05/18/2023) as evidenced by Ludwig et al. (Cancers, 04/04/2021).
Regarding claims 1 and 12, Kim et al. disclose substrate proteins recombinantly or chemically functionalized with a variety of bioactive peptides such as extracellular matrix-derived or growth factor-derived peptides (See entire document, Abstract). More specifically, Kim et al. disclose a substrate protein with the combination of an integrin activating motif and a heparin binding motif (Paragraph [0067]), wherein the substrate protein is MAPTRIX® containing an integrin binding motif, RGD (SEQ ID NO:15), and a heparin binding motif, SPPRRARVT (SEQ ID NO:18) (Paragraph [0103]). MAPTRIX® is a commercially available recombinant mussel adhesive protein (Paragraph [0061]).
Thus, Kim et al. anticipate instant claim 1 insofar as disclosing a recombinant mussel adhesive protein containing an integrin binding domain and a heparin binding domain. Additionally, it would be expected, absent evidence to the contrary, that the heparin binding motif disclosed by Kim et al. would necessarily be capable of binding or sequestering growth factors as heparin is known to bind growth factors (Paragraph [0074]).
Regarding claim 2, Kim et al. disclose the heparin binding motif is derived from fibronectin domain III (Paragraph [0067]).
Regarding claim 8, it is noted this is a functional limitation of the protein substrate of claim 1. This functional limitation does not materially change the structure of the protein substrate. Nonetheless, Kim et al. disclose heparin binding to TGFβ (Paragraph [0074]). Thus, it would be expected, absent evidence to the contrary, that the heparin binding motif disclosed by Kim et al. would necessarily be capable of binding to TGFβ.
Regarding claim 10, as discussed above, Kim et al. disclose RGD as the integrin binding motif. Kim et al. do not explicitly disclose RGD is capable of activating integrin avβ6. However, it would be expected, absent evidence to the contrary, that RGD would be capable of activating integrin avβ6 as evidenced by Ludwig et al. Ludwig et al. disclose the RGD-motif is recognized by multiple integrin subtypes, including avβ6 (Page 2, Last Paragraph).
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.
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.
Claims 1-2, 8, 10, 12 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 20160355780 A1, 12/08/2016) (IDS Reference of 05/18/2023) as evidenced by Ludwig et al. (Cancers, 04/04/2021).
The teachings of Kim et al. are discussed above.
Regarding claims 14 and 15, as discussed above, Kim et al. disclose MAPTRIX® containing an integrin binding motif and a heparin binding motif. Kim et al. further disclose the MAPTRIX® recombinant mussel adhesive protein comprises two mussel foot protein peptides wherein the second mussel foot peptide is linked to the first mussel foot peptide at the C-terminus, N-terminus or the C- and N-terminus (Paragraph [0062]).
Kim et al. do not disclose the integrin and/or heparin binding motif is bound to the N-terminal or C-terminal of the recombinant adhesive protein.
However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the integrin binding motif and/or the heparin binding motif, meaning one or both, would be bound to the N-terminal or C-terminal of the recombinant mussel adhesive protein because Kim et al. disclose the second mussel foot peptide is linked to the first mussel foot peptide at the C-terminus, N-terminus or the C- and N-terminus, therefore, it would have been obvious to link the other peptides contained in the protein, being an integrin motif and a heparin binding motif, to the C-terminus, N-terminus or the C- and N-terminus of the mussel foot peptides motivated by the desire to effectively link all of the peptides because that is how the other two peptides of the invention were linked.
Regarding claim 16, Kim et al. disclose the combinatorial motifs may include one or more spacers between two peptide motifs to optimize flexibility and/or solubility and to afford increased affinity and/or bioavailability (Paragraph [0082]). The combinatorial motifs may have a peptide spacer sequence of at least two amino acids, preferably 2-15 amino acids, appended to the C-termini of at least one of the two peptide motifs (Paragraph [0082]).
Claims 1-3, 8, 10, 12 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 20160355780 A1, 12/08/2016) (IDS Reference of 05/18/2023) as evidenced by Ludwig et al. (Cancers, 04/04/2021) in view of Kato et al. (Peptides, 1998).
The teachings of Kim et al. are discussed above.
Regarding claim 3, Kim et al. do not disclose the heparin binding motif from fibronectin domain III is instant SEQ ID NO: 12.
However, Kato et al. disclose sequences present in the C-terminal heparin-binding domain of fibronectin (See entire document, Abstract). Kato et al. further disclose the Arg-Gly-Asp (RGD) sequence in the central cell-binding domain has shown to be an important cell recognition site with specific integrins being receptors of RGD (Page 7, Left Column). The C-terminal heparin-binding domain of fibronectin has also been implicated in these events by an RGD-independent mechanism (Page 7, Right Column). This domain supports proteoglycan and integrin dependent adhesion of cells (Page 7, Right Column). Kato et al. go on to disclose a specific synthetic peptide sequence corresponding to residues Ala1819 to Lys1830 of the C-terminal heparin-binding domain of fibronectin with the amino acid sequence ANGQTPIQRYIK (Page 9, Left Column, Last Paragraph – Right Column, First Paragraph). The amino acid sequence ANGQTPIQRYIK shares 100% sequence identity to instant SEQ ID NO: 12, the elected heparin binding motif.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the amino acid sequence of ANGQTPIQRYIK disclosed by Kato et al. as the heparin binding domain derived from fibronectin because it was a known peptide sequence derived from the C-terminal heparin-binding domain of fibronectin as taught by Kato et al. as it amounts to simple substitution of one known element for another to obtain predictable results. Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B).
Claims 1-2, 8, 10, 12 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (US 20160355780 A1, 12/08/2016) (IDS Reference of 05/18/2023) as evidenced by Ludwig et al. (Cancers, 04/04/2021) in view of Broude et al. (US 20090029370 A1, 01/29/2009).
The teachings of Kim et al. are discussed above.
Regarding claim 17, Kim et al. do not disclose the spacer linker is instant SEQ ID NO: 75.
However, Broude et al. disclose polypeptide fragments that can be encoded by a single construct, including the polypeptide portion, a linker and a nucleic acid binding moiety polypeptide (Paragraph [0075]). The split-polypeptides can comprise a flexible linker (Paragraph [0107]). Multiple linkers may be used in order to take advantage of the desired properties of each linker, including flexible linkers that increase the solubility of the conjugates can be used (Paragraph [0108]). Broude et al. further disclose the use of a specific 10-amino acid (aa) flexible polypeptide linker, (Ser-Gly)5 (Paragraph [0197]). (Ser-Gly)5 corresponds to SGSGSGSGSG, which is the exact sequence of the peptide of instant SEQ ID NO: 75.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have utilized the 10-aa flexible polypeptide linker (Ser-Gly)5 as disclosed by Broude et al. in the substrate protein of Kim et al. motivated by the desire to create a protein substrate with adequate flexibility and solubility because Kim et al. specifically disclose spacers for optimizing flexibility and solubility wherein preferable spacers for their invention include peptide spacers between 2 and 15 amino acids in length and the (Ser-Gly)5 linker disclosed by Broude et al. is a known 10 aa long flexible spacer that can increase solubility and flexibility.
Conclusion
Claims 1-3, 8, 10, 12 and 14-17 are rejected.
No claims are allowed.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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