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 .
Status of Application, Amendments and/or Claims
The amendment, filed 10 April 2023, has been entered in full. Claims 3, 5, 9 and 11 are amended.
Applicant's election with traverse of Group I (claims 1-15) in the reply filed on 21 April 2026, is acknowledged. The traversal is on the ground(s) that the Office Action states the claims lack unity because the common technical feature -a recombinant monobody that specifically binds calreticulin and in which a calreticulin-binding peptide is inserted into the BC loop and/or FG loop of human fibronectin domain III (Fn3)- does not provide a contribution over the prior art, in view of Loew and Koide.
Applicant argues that they have amended independent claim 1 to clarify and narrow the claimed recombinant monobody. Applicant maintains that amended claim 1 is directed to a recombinant monobody which specifically binds calreticulin and in which a calreticulin-binding peptide consisting of the amino acid sequence of SEQ ID NO: 15 or 16 is inserted into at least one among the BC loop and the FG loop of human fibronectin domain III (Fn3). Applicant argues that the amended claim 1 no longer broadly encompasses any calreticulin-binding peptide inserted into an Fn3 loop and that claim 1 now requires a recombinant Fn3 monobody containing one of the specifically recited calreticulin-binding peptide sequences, namely SEQ ID NO: 15 or SEQ ID NO: 16.
Applicant argues that the cited references do not teach or suggest the specific sequence-limited recombinant monobody now recited in amended claim 1. Applicant maintains that at most, Loew is relied upon as disclosing calreticulin-binding constructs generally, and Koide is relied upon as disclosing Fn3 monobody scaffolds and modification of Fn3 loop regions generally, but the cited art does not disclose or suggest the presently claimed recombinant monobody in which a calreticulin-binding peptide consisting of SEQ ID NO: 15 or 16 is inserted into at least one of the BC loop and the FG loop of human Fn3.
Applicant’s arguments have been fully considered but are not persuasive. The previous claims, upon which the Restriction was made, recited a recombinant monobody which specifically binds calreticulin, wherein any calreticulin-binding peptide is inserted into a human fibronectin domain III (Fn3) loop. As was stated in the previous Office, the technical feature (i.e. the calreticulin-binding peptide modified human Fn3), is not a special technical feature as it does not make a contribution over the prior art in view of Loew et al. (WO 2019/139987; ELSTAR THERAEPEUTICS, INC. published July 18, 2019) and Koide (US Patent 6,703,199; published March 9, 2004). The requirement is still deemed proper and is therefore made FINAL.
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 21 April 2026.
The amendment, filed 21 April 2026, has been entered in full. Claims 3, 19 and 20 are canceled. Claim 1 is amended. Claims 1, 2, 4-15 are under examination.
Foreign Priority
Acknowledgment is made of Applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d). The certified copy KR 10-2020-0128843 has been placed of record in the file.
Because the document, upon which priority is claimed, is not in English it fails to provide adequate support. Therefore, the filing date of October 5, 2021 will be used for purposes of applying prior art. This date is the filing date of document 371 PCT/KR2021/013640.
Should Applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 4/6/2023 and 4/20/2026) were received and comply with the provisions of 37 CFR $1.97, 1.98 and MPEP § 609. They have been placed in the application file and the information referred to therein has been considered as to the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Applicant is reminded that a substitute sequence listing was submitted on 04 October 2023, but a substitute specification inserting the incorporation-by-reference paragraph was not. See also MPEP 2422.03 and 2422.03(a).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 102
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 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, 2, 9-15 are rejected under 35 U.S.C. 102(a1) as being anticipated by Zhang et al. (Reference submitted by Applicant; Cancers 13:pages 1-18; June 4, 2021).
Zhang et al. teach a recombinant monobody which specifically binds calreticulin wherein a calreticulin-binding peptide consisting of the amino acid sequence of instant SEQ ID NO: 15 and instant SEQ ID NO:16 is inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3)(abstract)(applies to claim 1 and 2). Zhang et al. teach the recombinant calreticulin-binding peptide monobody is conjugated to contrast compound Rluc8 (page 4, 1st full paragraph)(applies to claims 11-13).
It is noted that the instant claims are drawn to a product not a method of using the product. Therefore, the claim limitations “for treating cancer” and “for diagnosing or contrasting cancers” are merely the intended use of the product. Zhang et al. teach administering the recombinant monobody-Rluc8 conjugate to mice animal models of cancer (applies to claims 9, 10, 14 and 15).
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.
1. Claims 1, 2, 5-15 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Reference submitted by Applicant; Cancers 13:pages 1-18; June 4, 2021) in view of Fiset et al. (US 2023/0381309, published Nov 30, 2023, priority date Oct 13, 2020).
Zhang et al. teach a recombinant monobody which specifically binds calreticulin wherein a calreticulin-binding peptide consisting of the amino acid sequence of instant SEQ ID NO: 15 and instant SEQ ID NO:16 is inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3)(abstract)(applies to claim 1 and 2). Zhang et al. teach the recombinant calreticulin-binding peptide monobody is conjugated to contrast compound Rluc8 (page 4, 1st full paragraph)(applies to claims 11-13).
The claim limitations “for treating cancer” and “for diagnosing or contrasting cancers” are the intended use of the claimed product. Zhang et al. teach administering the recombinant calreticulin-binding peptide monobody-Rluc8 conjugate to mice animal models of cancer (applies to claims 9, 10, 14 and 15).
The instant specification teaches “as used herein, the term peptide conjugate refers to a complex in which protein and drug are combined as a formulation that allows for maintaining the long-term efficacy of peptide drugs” (paragraph 0052).
Zhang et al. teach administering doxorubicin to the mice animal model of cancer before administering the recombinant calreticulin-binding peptide monobody.
Zhang et al. do not teach administering doxorubicin to the mice animal model of cancer with the recombinant calreticulin-binding peptide monobody.
Fiset et al. teach methods for treating hematologic cancers such as diffuse large B cell lymphoma (DLBCL). Fiset et al. teach a therapeutic composition comprising a T cell activation therapeutic with an inhibitor of PD-L1 or an inhibitor of PD-1. Fiset et al. teach that the inhibitor of PD-1 or PD-L1 is an antibody or a monobody (abstract, paras 0009 and 0279). Fiset et al. teach the term monobody relates to a molecule based on the 10th extracellular domain of human fibronectin III (10Fn3)(para 0306).
Fiset et al. teach that the T cell activation therapeutic is a peptide antigen or a nucleic acid encoding the peptide antigen (para 0013). Fiset et al. teach that the p53 gene codes for a tumor-associated protein that has peptide sequences that can be incorporated as an additional antigen in the T cell activation therapeutic composition of the invention (para 0154)(applies to claims 5, 7 and 8). Fiset et al. teach that the therapeutic composition can further include doxorubicin (paras 0026 and 0331)(applies to claims 5 and 6).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify the recombinant calreticulin-binding peptide monobody, as taught by Zhang et al., by combining it with doxorubicin or p53, as taught by Fiset et al.
One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons. Zhang et al. teach employing the recombinant calreticulin-binding peptide monobody to detect cell death in cancer chemotherapy. Doxorubicin is well known in the art as a chemotherapy drug that treats various cancers. The tumor suppressor p53 is well known in the art as a tumor suppressor. Based on the teachings it would be obvious to use doxorubicin or p53 with the recombinant calreticulin-binding peptide monobody.
2. Claims 1, 2, 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Loew et al. (Reference of record, WO 2019/139987; ELSTAR THERAEPEUTICS, INC. published July 18, 2019) in view of Koide (Reference of record; US Patent 6,703,199; published March 9, 2004) and Dehar (US 2003/0060613; published March 27, 2003).
Loew et al. teach nucleic acid constructs and polypeptides related to antigen binding domains that bind to mutant calreticulin and using them in methods to treat cancer (abstract). The instant claim limitations “for treating cancer” is the intended use of the claimed product (applies to claims 9 and 10).
Loew et al. teach in some embodiments the construct comprises a sequence encoding an antibody domain comprising a mutant calreticulin binding domain (paras 0007-0009, 0054, 0056). Loew et al. teach a composition comprising a polypeptide encoded by a nucleic acid described herein. Loew et al. teach that in some embodiments, the polypeptide is an antibody or fragment thereof. In some embodiments, the antibody domain is a monoclonal antibody domain, a human antibody domain, a humanized antibody domain or a chimeric antibody domain (paras 0048-0056).
Loew et al. teach that the term "antibody fragment" refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen. Loew et al. teach that the antigen binding fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (para 0098). Loew et al. teach that antigen binding fragments can also be grafted into scaffolds based on polypeptides such as fibronectin type III (Fn3). Loew et al. teach U.S. Pat. No. 6,703,199 and states that the U.S. Patent describes fibronectin polypeptide minibodies)(para 0098)(applies to claim 1).
Loew et al. do not teach that the calreticulin antigen binding fragment is inserted into at least the BC loop or the FG loop of human Fn3. Loew et al. do not teach that the calreticulin antigen binding peptide fragment consists of the amino acid sequence of instant SEQ ID NO:15 or instant SEQ ID NO:16.
Koide teaches a human fibronectin type III (Fn3) polypeptide monobody, a nucleic acid molecule encoding said monobody, and a variegated nucleic acid library encoding said monobody. Koide teaches methods of preparing a Fn3 polypeptide monobody. Koide teaches that the Fn3 polypeptide is modified by insertions in the BC loop and/or the FG loop. Koide teaches the insertion of a preselected DNA segment yields a DNA molecule which encodes a polypeptide monobody having an insertion. The DNA molecule is then expressed so as to yield the polypeptide monobody (abstract; column 1, lines 15-22 and column 4, lines 24-61 and Figures)(applies to claims 1 and 2).
Dehar teaches isolated and purified proteins, such as calreticulin and mimetics of calreticulin for modulating hormone responsiveness. Dehar teaches that these proteins are useful in gene therapy and in manufacturing pharmaceuticals for treating cancer. Dehar teaches that the proteins include KXFFYR, wherein X is either G, A or V and Y is either K or R (abstract and para 0001). Dehar teaches a calreticulin binding peptide sequence (KLGFFKR, SEQ ID NO:7) that is 100% identical to instant SEQ ID NO:15. See below, Sequence Search Result A (applies to claim 1). Dehar teaches that peptides based on the KXFFYR sequence can be used to modulate hormone responsiveness by influencing the binding of calreticulin to the hormone receptors in live cells. Dehar teaches an experiment wherein the KLGFFKR peptide was able to effectively compete for calreticulin binding with the KGFFRR sequence in the retinoic acid receptor (para 0095).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a construct wherein a calreticulin-antigen binding fragment is inserted into fibronectin type III (Fn3), as taught by Loew et al., wherein the insertion site is the BC loop and/or FG loop, as taught by Koide and wherein the calreticulin-antigen binding fragment consists of instant SEQ ID NO:15, as taught by Dehar. One ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons. Both Loew and Dehar teach that calreticulin-binding sequences can be used for cancer treatment. Koide teaches that large variations seen in the BC and FG loops suggests that these particular loops are not crucial to stability. Based on the teachings, it would be obvious to modify the calreticulin-binding-Fn3 monobody taught by Loew by inserting a calreticulin binding peptide sequence (KLGFFKR) taught by Dehar, into BC loop or the FG loop of human Fn3, as taught by Koide.
2a. Claims 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Loew et al. in view of Koide and Dehar, as applied to claims 1 and 2 above, and further in view of Qvortrup (US 2022/0387615; published Dec 8, 2022, priority date June 26, 2019) and Schmit et al. (Targeted protein degradation through cytosolic delivery of monobody binders using bacterial toxins. ACS Chem. Biology 14:916-924; 2019).
The teachings of Loew, Koide and Dehar are described above. The combined references teach a recombinant monobody which specifically binds calreticulin and in which a calreticulin-binding peptide consisting of the amino acid sequence of SEQ ID NO: 15 is inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3).
The references do not teach wherein an anticancer compound or an anticancer protein is bound to the recombinant monobody by a covalent or non-covalent bond.
Qvortrup teaches an enzyme cleavable linker platform conjugated to a drug or a diagnostically relevant compound, a biomolecule, and an enzyme cleavable group (abstract). Qvortrup teaches attaching an antibody or a monobody to the disclosed enzyme cleavable linker, wherein the antibody or monobody is selected based on the ability to access and contact cellular targets (paras 0181-0182, 0185-0186 and 0193). Qvortrup teaches attaching anticancer compounds camptothecin or auristatin to the antibody or monobody (paras 0210, 0268 and 0269 (applies to claims 5, 6, 9, 10).
Schmit et al. teach that monobodies are small engineered binding proteins that, upon expression in cells, can inhibit signaling of cytosolic oncoproteins with outstanding selectivity. Schmit et al. teach that efficacy may be further increased by inducing degradation of monobody targets through fusion to von Hippel−Lindau (VHL)(applies to claims 5, 7, 8, 9 and 10)(abstract).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a monobody wherein a calreticulin-antigen binding fragment is inserted into fibronectin type III (Fn3), wherein the insertion site is the BC loop and/or FG loop, wherein the calreticulin-antigen binding fragment consists of instant SEQ ID NO:15, as taught by Loew, Koide and Dehar, respectively, by attaching an anticancer compound or an anticancer protein, as taught by Qvortrup and Schmit et al., respectively. One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons. Camptothecin and auristatin are well known in the art to be employed in anti-cancer therapies. The von Hippel−Lindau protein is a tumor suppressor. Based on the teachings it would be obvious to use camptothecin, auristatin and/or von Hippel−Lindau with the recombinant calreticulin-binding peptide monobody.
2b. Claims 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Loew et al. in view of Koide and Dehar, as applied to claims 1 and 2 above, and further in view of Kim et al. (Engineering of monobody conjugates for humanEphA2-specific optical imaging. PLoS ONE 12(7): e0180786, 14 pages; 2017).
The teachings of Loew, Koide and Dehar are described above. The combined references teach a recombinant monobody which specifically binds calreticulin and in which a calreticulin-binding peptide consisting of the amino acid sequence of SEQ ID NO: 15 is inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3).
The references do not teach wherein a compound for contrast is bound to the recombinant monobody by a covalent or non-covalent bond.
Kim et al. teach a monobody conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8, i.e. blue fluorescent protein) or enhanced green fluorescent protein (EGFP)(applies to claims 11-13). The claim limitations “for diagnosing or contrasting cancers” are the intended use of the claimed product. Kim et al. teach the monobody-optical reporter conjugate detected tumor specific luminescence signals in PC3 xenograft mice (abstract) (applies to claims 14 and 15).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a monobody wherein a calreticulin-antigen binding fragment is inserted into fibronectin type III (Fn3), wherein the insertion site is the BC loop and/or FG loop, wherein the calreticulin-antigen binding fragment consist of instant SEQ ID NO:15, as taught by Loew, Koide and Dehar, respectively, by attaching an optical reporter such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) to the monobody, as taught by Kim et al. One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success because Kim et al. teach that many reporter proteins, such as Rluc8 or EGFP, are used for optical imaging.
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, 2, 4-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-15 and 18, of copending Application No. 18/854,647 (reference application) in view of Kim et al. (Engineering of monobody conjugates for humanEphA2-specific optical imaging. PLoS ONE 12(7): e0180786, 14 pages; 2017).
The instant claims are drawn to a recombinant monobody which specifically binds calreticulin and in which a calreticulin-binding peptide consisting of the amino acid sequence of SEQ ID NO: 15 or 16 is inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3). The claims are further drawn to wherein the recombinant monobody is composed of an amino acid sequence selected from the group consisting of SEQ ID NOs: 7 to 12. The claims are further drawn to a peptide conjugate comprising the recombinant monobody and an anticancer compound or an anticancer protein such as doxorubicin, asparaginase or p53. The claims are further drawn to a pharmaceutical composition for treating cancer comprising the recombinant monobody. The claims are further drawn to a peptide conjugate comprising the recombinant monobody and a compound for contrast such as green fluorescent protein (GFP) or blue fluorescent protein (BFP).
The claims of copending Application No. 18/854,647 teach a fusion protein comprising a recombinant monobody which specifically binds to calreticulin and an L-asparaginase linked to the C-terminus of the recombinant monobody, wherein the recombinant monobody has a peptide that specifically binds to the calreticulin inserted into the BC loop and the FG loop of human fibronectin domain III (Fn3). The claims further teach wherein the recombinant monobody comprises amino acids represented by SEQ ID NO: 9 or 10.
The claims of copending Application No. 18/854,647 teach wherein the recombinant monobody has a calreticulin-binding peptide represented by SEQ ID NO: 15 inserted into the BC loop of the human fibronectin domain III and a calreticulin-binding peptide represented by SEQ ID NO: 16 inserted into the FG loop or has a calreticulin- binding peptide represented by SEQ ID NO: 16 inserted into the BC loop and a calreticulin-binding peptide represented by SEQ ID NO: 15 inserted into the FG loop.
The claims of copending Application No. 18/854,647 further teach a pharmaceutical composition for the treatment of solid tumors, comprising the fusion protein. The claims teach the pharmaceutical composition further comprising one or more anti-cancer compounds, tumor suppressor proteins, or anticancer proteins such as doxorubicin and p53.
The claims of copending Application No. 18/854,647 do not teach wherein a compound for contrast is bound to the recombinant monobody by a covalent or non-covalent bond.
Kim et al. teach a monobody conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8, i.e. blue fluorescent protein) or enhanced green fluorescent protein (EGFP)(applies to claims 11-13). The claim limitations “for diagnosing or contrasting cancers” are the intended use of the claimed product. Kim et al. teach the monobody-optical reporter conjugate detected tumor specific luminescence signals in PC3 xenograft mice (abstract) (applies to claims 14 and 15).
Although the claims at issue are not identical, they are not patentably distinct from each other. It would have been obvious for one of ordinary skill in the art before the effective filling date to modify the recombinant calreticulin-binding peptide monobody, as taught by the claims of copending Application No. 18/854,647, by attaching an optical reporter such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) to the monobody, as taught by Kim et al.
One of ordinary skill in the art would have been motivated to make such modifications and expect success for the following reasons. The claims of copending Application No. 18/854,647 teach inserting a calreticulin binding peptide into the BC loop and the FG loop of human fibronectin domain III (Fn) SEQ ID Nos 9, 10, 15 and 16, which are 100% identical to instant SEQ ID Nos: 9, 10, 15 and 16 (sequence search alignment provided upon request). In addition, the claims of copending Application No. 18/854,647 teach a pharmaceutical composition comprising the calreticulin binding peptide modified human fibronectin domain III and the same anti-cancer compounds, tumor suppressor proteins and/or anticancer proteins. Kim et al. teach that many reporter proteins, such as Rluc8 or EGFP (i.e. compounds for contrast), are used for optical imaging.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
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/R.M.D/Examiner,ArtUnit1647
5/14/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
SEQUENCE SEARCH RESULT A
This page gives you Search Results detail for the Application 18030584 and Search Result 20260427_142509_us-18-030-584a-15.minpct99.rapbm
Title: US-18-030-584A-15
Perfect score: 37
Sequence: 1 KLGFFKR 7
SUMMARIES
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 37 100.0 7 US-09-997-961-7 2001-11-29 15 NOVEL USE OF CALRETICULIN IN MODULATING HORMONE RESPONSIVENESS AND NEW PHARMACEU
RESULT 1
US-09-997-961-7
Sequence 7, US/09997961
Publication No. US20030060613A1
GENERAL INFORMATION
APPLICANT: DEDHAR, Shoukat
TITLE OF INVENTION: NOVEL USE OF CALRETICULIN IN MODULATING
TITLE OF INVENTION: HORMONE RESPONSIVENESS AND NEW PHARMACEUTICALS FOR
TITLE OF INVENTION: TREATING CANCER, OSTEOPOROSIS AND CHRONIC INFLAMMATORY
TITLE OF INVENTION: DISEASE
CURRENT APPLICATION NUMBER: US/09/997,961
CURRENT FILING DATE: 29-Nov-2001
PRIOR APPLICATION NUMBER: US/09/169,935
PRIOR FILING DATE: <Unknown>
PRIOR APPLICATION NUMBER: US/08/377,432
PRIOR FILING DATE: 24-JAN-1995
NUMBER OF SEQ ID NOS: 49
SEQ ID NO 7
LENGTH: 7
TYPE: PRT
Query Match 100.0%; Score 37; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KLGFFKR 7
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Db 1 KLGFFKR 7
Prosecution Insights