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's election with traverse of Group I, claims 1-11 and 16-19 in addition to the species of SEQ ID NO: 34 (comprising SEQ ID NO: 94-96) and cancer, in the reply filed on 8/18/2025 is acknowledged. The traversal is on the ground(s) that restriction is improper because Groups I-III relate to the same general inventive concept and/or share the same technical feature, and Baumann neither anticipates nor makes obvious the special technical feature. This is not found persuasive.
As stated in the restriction requirement, Groups I, II, and III lack unity of invention because even though the inventions of these groups require the technical feature of a recombinant binding protein comprising an ankyrin repeat domain, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Baumann (US2015/368302 A1, published 12/24/15), listed on the International Search Report.
Baumann teaches ankyrin repeat proteins within binding specificity for platelet-derived growth factor (PDGF) protein dimer BB (PDGF-BB) as well as nucleic acids encoding such PDGF binding proteins and pharmaceutical compositions. SEQ ID NO: 19 of Baumann exhibits 81.8% identity to the instant SEQ ID NO: 96. The instant SEQ ID NO: 96 is 33 amino acids in length. Claim 1 allows for up to 9 substitutions or variants with 72.7% sequence identity to SEQ ID NO: 96. Therefore SEQ ID NO: 19 of Baumann meets this limitation. Further, one of ordinary skill in the art would recognize that the functional characteristics of proteins rely on their structure, and, based on sequence identity, one would reasonably expect that SEQ ID NO: 19 of Baumann, which meets the structural limitations set forth by claim 1, would have binding specificity for FAP in addition to PDGF-BB. Thus, the common technical feature among the instant claims is not a special technical feature as it does not make a contribution over the prior art in view of Baumann, making restriction proper.
Further, as provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
The instant application claims multiple methods of use in addition to a product. This further means unity of invention is lacking and restriction is proper.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-20 are pending under examination. Claims 6, 12-15, and 20 have been withdrawn as non-elected species (claim 6) and inventions (claims 12-15 and 20). Claims 1-3, 5-11, and 14 are currently amended. Claims 16-20 are new.
Priority
The instant application is the 371 national stage entry of PCT/EP2020/065317, filed 6/3/2020, which claims priority to EP19178277.0, filed 6/4/2019. The priority date of 6/4/2019 is acknowledged.
Information Disclosure Statement
The IDS submitted on 12/2/2021 is under consideration.
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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specifically, indicate in the Brief Description of the Figures that #1 is SEQ ID NO: 1, etc.
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.
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.
Specifically, include the Incorporation by Reference statement on the first page of the specification.
Specific deficiency – The "Sequence Listing" has not been entered into the application because the required statement of no new matter is missing. See 37 CFR 1.825(a)(4) or 1.825(b)(5).
Required response – Applicant must provide:
A proper statement of no new matter.
Because the latest CRFE was filed after the initial filing date, a statement of no new matter is required.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Pg 53, line 38). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2, 5, and 19 are objected to because of the following informalities:
Claim 2 – “SEQ ID NOs:” is repeated twice in line 4.
Claim 5 – “the second last” in line 6 should read as “the second to last” (emphasis added).
Claim 19 – “the” is repeated twice in line 1.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites “A recombinant binding protein comprising an ankyrin repeat domain… wherein said ankyrin repeat domain comprises an ankyrin repeat module comprising an amino acid sequence selected from the group consisting of (1) SEQ ID NO: 48-134 and (2) one or more sequences in which up to 9 amino acids in any of SEQ ID NO: 48-134 are exchanged by another amino acid” (emphasis added). This claim is being interpreted to mean that a peptide meeting the limitations of (1) or (2), wherein a peptide or protein encompasses or contains the entirety of any one of the sequence, meets the limitation of the claim. Conversely, smaller fragments encompassed by any one of the sequences (i.e., dipeptides) are being interpreted as not meeting the limitations of the claim. This interpretation is being applied to all claims that recite “an amino acid”.
Claim 1 further recites a recombinant binding protein that has “binding specificity for fibroblast activation protein (FAP)”. This limitation describes a functional rather than a structural element of the instant invention. As such, the claim is being interpreted based upon the structural limitation (1 or 2, as recited above), where the functional limitation is a property endowed by the structure.
Claims 8, 16, 17, and 18 each recite additional functional limitations. As stated above, the claim is being interpreted based upon the structural limitation (SEQ ID NO: 48-134 or SEQ ID NO: 48-134 with up to 9 substitutions), where the functional limitation is a property endowed by the structure.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 8-11, and 16-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a recombinant binding protein comprising an ankyrin repeating domain that can bind to fibroblast activation protein (FAP) and comprises an ankyrin repeat module comprising an amino acid sequence selected from the group consisting of (1) SEQ ID NO: 48-134 and (2) one or more sequences in which up to 9 amino acids in any of SEQ ID NO: 48-134 are exchanged by another amino acid. Claims 2-4, 8-11, and 16-19 depend from claim 1.
Claim 5 is drawn to a recombinant binding protein comprising an ankyrin repeat domain that can bind to FAP and comprises an amino acid sequence with at least 80% amino acid sequence identity with any one of SEQ ID NO: 1-35 and 144-153, wherein G at position 1 and/or S at position 2 of SEQ ID NO: 1-35 and 144-153 are missing, and wherein L at the second to last position and/or N at the last position is exchanged by A.
The rejection is based on the limitations 1) “up to 9 amino acids in any of SEQ ID NO: 48-134 are exchanged by another amino acid” from claim 1 and 2) “at least 80% amino acid sequence identity with any one of SEQ ID NO: 1-35 and 144-153” from claim 5. These limitations do not disclose sufficient structure-function relationship to meet the written description requirement.
The claims require that 1) any variant of SEQ ID NO: 94-96, which constitute the elected SEQ ID NO: 34, that has up to 9 amino acid substitutions or 2) any variant with at least 80% sequence to SEQ ID NO: 34 identity, bind to FAP. The core structure or the residue(s) of SEQ ID NO: 94-96 and 34 that directly interact with CD38 is unknown. The claims do not indicate any positional information (i.e., where the substitutions should occur in the sequence) nor restrict the type of amino acid used in a substitution (i.e., it does not specify that the substitution should be a conservative substitution).
Kelly et al. (US 20060058228, published 3/16/2006) discuss a phage display screen to identify peptides that distinguish between well-differentiated (HCT116) and poorly-differentiated (HT29) colon cancer cell lines. Analysis of the selected library resulted in the identification of a nine amino acid, disulfide-constrained peptide having a three amino acid (arg-pro-met, “RPM”) motif that specifically binds HT29 cells ([0032]). Substituting each of RPM with alanine significantly limited or abolished the ability of the peptide to compete with wild type RPM in a binding assay, indicating that these three residues alone accounted for the ability to bind to HT29 cells ([0034]). In contrast to this example, it is unknown which residues of SEQ ID NO: 94-96 and 34 directly engage FAP. Thus, one cannot extrapolate how 1-9 substitutions introduced to any position of SEQ ID NO: 94-96 and 80% sequence identity to SEQ ID NO: 34 might impact their functionality.
Further, Guo (H.H. Guo,J. Choe, & L.A. Loeb, Protein tolerance to random amino acid change, Proc. Natl. Acad. Sci. U.S.A. 101 (25) 9205-9210, (2004).) teaches that a protein’s tolerance to random substitutions ultimately depends on whether the residues at hand are involved the protein’s functional activity. For instance, regions that were highly substitutable in the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG) include the first 79 N-terminal residues previously demonstrated to be unnecessary for in vitro enzyme activity and DNA binding specificity. In contrast, residues that are involved in glycosylase function or DNA binding did not tolerate amino acid substitutions (“Substitutability and Structure”, Pg 9207-9209; Figure 1). Figure 1 of Guo also indicates that tolerated substitutions are generally conservative, i.e., a nonpolar residue is substituted for another nonpolar residue, etc. However, there are no explicit limitations in the instant claims regarding the type of substitutions that can be made relative to SEQ ID NO: 94-96 and/or 34.
Applicants have not disclosed variants of SEQ ID NO: 94-96 with any number of substitutions nor variants with 80% sequence identity to SEQ ID NO: 34.
SEQ ID NO: 94-96 are each 33 amino acids in length. As there are no positional limitations on where the amino acid substitutions should be, this allows for more than (33!*19) + (33*19) = 1.65xe^38 possible variants where only 1-2 substitutions occur (33! possible combinations of two substitutions in a peptide with 33 positions * 19 naturally-occurring amino acids not including the amino acid present in the wild-type sequence; plus 33 possible positions wherein one substitution occurs * 19 naturally-occurring amino acids not including the amino acid present in the wild-type sequence).
SEQ ID NO: 34 is 159 amino acids; sequences having at least 80% sequence identity would require 128 of the amino acids to be maintained (i.e. 128/159*100 = 80.5%) and would allow up to 31 amino acids (i.e. 159-128 = 31) to be substituted. Consequently, there are more than 9.29e^32 possible ways to select up to 31 residues from the 159 residues in the sequence that are free to be modified (i.e. x = n!/(r!(n-r)!)); each of which could be substituted with any of the other 19 naturally occurring common amino acids (i.e., that number multiplied by 19).
Consequently, it is unknown whether all variants encompassed within the range of 1) up to 9 substitutions in one of SEQ ID NO: 94-96 and 2) 80% sequence identity to SEQ ID NO: 34 would retain the structural, chemical, and/or physical properties required to bind to FAP. Therefore, the instant specification does not provide adequate written description to possess the broad genus described above since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
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.
(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.
Claim(s) 1 and 2 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bakker et al. (US 20160289285 A1, published 10/6/2016).
Bakker teaches SEQ ID NO: 13, which has two substitutions relative to the instant SEQ ID NO: 94, as shown below:
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Thus, Bakker anticipates the instant claims 1 and 2.
Claim(s) 1 and 2 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Binz et al. (US 9,221,892 B2, published 12/29/2015).
Binz teaches SEQ ID NO: 22, which has four substitutions relative to the instant SEQ ID NO: 95, as shown below:
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Thus, Binz anticipates the instant claims 1 and 2.
Claim(s) 1 and 2 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Fiedler et al. (US 20150299265 A1, published 10/22/2015).
Fielder teaches SEQ ID NO: 108, which has four substitutions relative to the instant SEQ ID NO: 96, as shown below:
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Thus, Fielder anticipates the instant claims 1 and 2.
Claim(s) 1-4, 8-11, and 16-19 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Baumann (US 9,163,070 B2, published 10/20/2015).
Baumann teaches ankyrin repeat proteins with binding specificity for platelet-derived growth factor dimer BB (PDGF-BB) as well as nucleic acids, pharmaceutical compositions, and methods to treat disease (Abstract).
Baumann teaches SEQ ID NO: 58, as shown below:
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Box 1 represents the instant SEQ ID NO: 94 with 5 mutations relative to SEQ ID NO: 58 of Baumann; the region between Box 1 and Box 3 represents the instant SEQ ID NO: 95 with 6 mutations relative to SEQ ID NO: 58 of Baumann; and Box 3 represents the instant SEQ ID NO: 96 with six mutations relative to SEQ ID NO: 58 of Baumann. Thus, Baumann anticipates the instant claims 1-4. Additionally, because SEQ ID NO: 58 of Baumann meets the structural limitations of claim 1 and encompasses SEQ ID NO: 94, 95, and 96 with less than 9 substitutions in each individual segment, the functional characteristics of SEQ ID NO: 94, 95, and 96 must be retained by the structure of SEQ ID NO: 58. Thus, claims 8 and 16-18 are also anticipated.
Baumann further teaches that the recombinant PDGF-BB binding proteins or domains can be covalently bound to additional moieties, including a moiety that binds to a different target to create a dual-specificity binding agent, a bioactive compound, a labeling moiety (e.g. a fluorescent label such as fluorescein, or a radioactive tracer), a moiety that facilitates protein purification (e.g. a small peptide tag, such as a His- or strep-tag), a moiety that provides effector functions for improved therapeutic efficacy (e.g. the Fc part of an antibody to provide antibody-dependent cell-mediated cytotoxicity, a toxic protein moiety such as Pseudomonas aeruginosa exotoxin A (ETA) or a small molecular toxic agent such as maytansinoids or DNA alkylating agents) or a moiety that provides improved pharmacokinetics. Improved pharmacokinetics may be assessed according to the perceived therapeutic need (Col. 19, lines 52-66). The instant specification defines a bioactive molecule as any molecule that has a biological effect or activity in a mammal, including a human, and that can be covalently or non-covalently linked, conjugated, fused or otherwise physically associated with a binding protein of the invention (Pg 54, lines 8-11). Thus, claim 9 is anticipated.
Baumann further teaches nucleic acids that encode the peptides (Abstract; Col. 20, lines 21-26), thus anticipating claim 10.
Baumann further teaches pharmaceutical compositions comprising either the binding protein or the nucleic acid and a pharmaceutically acceptable carrier and/or diluent (Col. 20, lines 27-34). Thus, claims 11 and 19 are anticipated.
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.
Claim(s) 1-5, 7-11, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Baumann (US 9,163,070 B2, published 10/20/2015) in view of Binz et al. (US 9,221,892 B2, published 12/29/2015).
The teachings of Baumann have been set forth above; specifically, as shown above, SEQ ID NO: 58 exhibits >80% sequence identity to the elected SEQ ID NO: 34. Baumann does not teach a variant with ≥80% sequence identity wherein G at position 1 and/or S at position 2 are missing and wherein L at the second last position and/or N at the last position of is A.
Binz teaches improved N-terminal and C-terminal capping molecules for designed ankyrin repeat proteins (DARPins) that confer improved thermal stability (Abstract). Specifically, Binz teaches a version of the N-terminal capping molecule identical to Box 0 where G at position 1 and/or S at position 2 is missing (Col. 2, lines 10-11; claim 7):
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Binz also teaches a preferred C-terminal capping molecule is QDKSGKTPADLAADAGHEDIAEVLQKAA (SEQ ID NO: 9; Col. 12, lines 53-55), wherein the second to last and last positions of the C-terminus are occupied by A residues.
Thus, regarding claims 5 and 7, Baumann teaches a recombinant binding protein comprising an ankyrin repeat domain that binds FAP and exhibits >80% sequence identity to the instant SEQ ID NO: 34. Binz teaches an N-terminal capping molecule for DARPins missing the G and/or S at positions 1 and 2, respectively, as well as a preferred C-terminal capping molecule containing “AA” at the very C-terminus, both of which improve DARPin thermal stability. Therefore, it would be prima facie obvious to substitute the N-terminal and C-terminal capping molecules of SEQ ID NO: 58 taught by Baumann for those taught by Binz in order to improve the thermal stability of the protein. One skilled in the art would have a reasonable expectation of success as Binz already established that these specific capping molecules could improve the thermal stability of other similar proteins.
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 1-5, 7-8, 10, 11, and 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-12, 14, 16, and 18 of U.S. Patent No. 12,331,090 B2 (US ‘090) in view of Binz et al. (US 9,221,892 B2, published 12/29/2015). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 10 of US ‘090 recites a recombinant protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 5, wherein said recombinant protein binds human FAP, human CD40, and human serum albumin with a KD value of or below 100 nM. SEQ ID NO: 5 of US ‘090 encompasses and is >98% identical to the instant SEQ ID NO: 34.
US ‘090 does not teach removal of the G and/or S at positions 1, and 2, respectively.
Binz teaches improved N-terminal and C-terminal capping molecules for designed ankyrin repeat proteins (DARPins) that confer improved thermal stability, including removal of G and/or S at positions 1 and 2 of the N-terminal capping molecule.
Therefore, it would be prima facie obvious to substitute the N-terminal capping molecule for the one taught by Binz in order to improve the thermal stability of the protein. One skilled in the art would have a reasonable expectation of success as Binz already established that these specific capping molecules could improve the thermal stability of other DARPins.
Dependent claims further include the percent identity to SEQ ID NO: 5 (claims 11, 12, 18), the FAP inhibition activity (claim 14), and a pharmaceutical composition containing the recombinant protein (claim 16).
Claims 1-2, 8, 10, 11, and 16-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15, 20, and 21 of U.S. Patent No. US11,578,427 B2 (US ‘427). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 1 of US ‘427 recites a designed ankyrin repeat domain comprising an N-terminal capping module having a leucine (L), valine (V), isoleucine (I), methionine (M), or alanine (A) at a position corresponding to position 15 of SEQ ID NO: 69. Dependent claims 10, 14, and 15 further recite a protein comprising the ankyrin repeat domain, wherein the ankyrin repeat domain has an amino acid sequence selected from SEQ ID NO: 10, 11, 13-15, 17-19, 21-23, 118-140 and 142 (claim 14) and 25, 26, 28-30, 32-34, 36-38, 40, 41, 43-45, 47-49, 51-53, 55, 56, 58-60, 62-64, 66-68, and 115-117 (claim 15). SEQ ID NO: 94 has four or fewer mutations relative to SEQ ID NO: 13-15, 28-30, 43-45, and 58-60; SEQ ID NO: 95 has four or fewer mutations relative to SEQ ID NO: 131 and 134; and SEQ ID NO: 96 has four or fewer mutations relative to SEQ ID NO: 17-19, 134, and 136, thus anticipating instant claims 1-2, 8, and 16-18.
Dependent claims further include a nucleic acid encoding the ankyrin repeat domain (claim 20) and a pharmaceutical composition (claim 21).
Claims 1-2, 8-11, and 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9, 10, 14, 15, 19-21 of U.S. Patent No. US11,466,062 (US ‘062). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 1 of US ‘062 recites a recombinant binding protein comprising an amino acid sequence wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs 1 to 11, 76, 77 and 85. SEQ ID NO: 95 has five mutations relative to SEQ ID NO: 2; and SEQ ID NO: 96 has three mutations relative to SEQ ID NO: 6, thus anticipating instant claims 1-2, 8, and 16-18.
Additional independent claims include a recombinant binding protein comprising a first ankyrin repeat domain, wherein said first ankyrin repeat domain comprises a first amino acid sequence, wherein the first amino acid sequence is selected from the group consisting of SEQ ID NOs 1 to 11, 76, 77 and 85 (claim 4), and a recombinant binding protein comprising an amino acid sequence, wherein the amino acid sequence is selected from the group consisting of SEQ ID NOs: 12-42, 75, 84, 87 and 88 (claim 14). SEQ ID NO: 95 also has five mutations relative to SEQ ID NO: 13 and 39; SEQ ID NO: 96 also has three mutations relative to SEQ ID NO: 12, 14-16, 18, 20-24, 26, 30, 31, 33, 34, 36, 38, 40, and 42. Thus claims 1-2, 8, and 16-18 are anticipated.
Dependent claims further include a nucleic acid encoding the ankyrin repeat domain (claim 2 and 20), a pharmaceutical composition (claim 3 and 21), functional characteristics of the recombinant binding protein (claim 9 and 19), the addition of a serum albumin binding domain (claim 10), and the recombinant binding domain is SEQ ID NO: 31 (claim 15).
Claims 1-2, 8, 10-11, and 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 10, 14, 15, 19, and 20 of U.S. Patent No. US11,834,504 (US ‘504). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 1 of US ‘504 recites a recombinant protein comprising (1) a first binding agent that specifically binds to a protein expressed on the surface of an immune cell, and (2) at least two binding agents that specifically bind to a tumor-associated antigen, wherein said two binding agents specifically bind to different tumor-associated antigens, and wherein said first binding agent is a designed ankyrin repeat domain with binding specificity for CD3, and wherein said ankyrin repeat domain with binding specificity for CD3 comprises an amino acid sequence that is at least 85% identical to any one of the amino acid sequences of SEQ ID NOs: 1 to 5. Dependent claims further recite the recombinant peptide of claim 1, wherein it is at least 80% identical to any one of SEQ ID NO: 11-14, 78-86, and 95-101 (claims 9, 10, 14, 15). SEQ ID NO: 96 has four mutations relative to SEQ ID NO: 100, thus anticipating instant claims 1-2, 8, and 16-18.
Dependent claims further include a nucleic acid encoding the recombinant protein (claim 19) and a pharmaceutical composition (claim 20).
Claims 1-5, 7-8, 10, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20, 21, and 25 of copending Application No. 17/925,144 (‘144 reference application, claim set filed 11/24/2023) in view of Binz et al. (US 9,221,892 B2, published 12/29/2015). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 20 of copending Application No. ‘144 recites a nucleic acid encoding a protein, wherein said protein comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 5, and wherein said protein specifically binds serum albumin, fibroblast activation protein (FAP) and CD40. SEQ ID NO: 5 has two substitutions relative to the elected SEQ ID NO: 34, resulting in >98% sequence similarity.
Copending Application No. ‘144 does not teach removal of the G and/or S at positions 1 and 2 of SEQ ID NO: 34 respectively.
Binz teaches improved N-terminal and C-terminal capping molecules for designed ankyrin repeat proteins (DARPins) that confer improved thermal stability, including removal of G and/or S at positions 1 and 2 of the N-terminal capping molecule in the instant SEQ ID NO: 34.
Therefore, it would be prima facie obvious to substitute the N-terminal capping molecule for the one taught by Binz in order to improve the thermal stability of the protein. One skilled in the art would have a reasonable expectation of success as Binz already established that these specific capping molecules could improve the thermal stability of other DARPins.
Dependent claims further include the percent identity to SEQ ID NO: 5 or SEQ ID NO: 6 (claim 21; SEQ ID NO: 6 encompasses and exhibits 100% sequence identity to the instant SEQ ID NO: 34) and a pharmaceutical composition containing the nucleic acid (claim 25).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7-9, 11, and 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 11 of copending Application No. 18/267,282 (‘282 reference application, claim set filed 7/17/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘282 recites a composition comprising (i) a binding moiety and (ii) a drug molecule; wherein said binding moiety reversibly binds to said drug molecule; and wherein said binding moiety, when bound, inhibits a biological activity of said drug molecule. Dependent claim 9 recites the composition of claim 1, wherein said binding moiety comprises a designed ankyrin repeat domain, and dependent claim 11 recites the composition of claim 9 wherein said designed ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) SEQ ID NO: 1-10 and (2) sequences that have at last 85% amino acid sequence identity with any of SEQ ID NO: 1-10. The elected SEQ ID NO: 34 exhibits >80% sequence identity to SEQ ID NO: 6 of copending Application No. ‘282, wherein the G and S are missing at positions 1 and 2 of the N-terminus, respectively, and the C-terminus culminates with “AA”, thus meeting the limitations of the instant claims 1-5, 7-9, 11, and 16-18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7-8, and 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of copending Application No. 18/281,156 (‘156 reference application, claim set filed 8/12/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 2 of copending Application No. ‘156 recites a recombinant binding protein comprising an ankyrin repeat domain, wherein said ankyrin repeat domain has binding specificity for human CD33, and wherein said ankyrin repeat domain comprises an amino acid sequence with at last 85% amino acid sequence identity with any one of SEQ ID NO: 1-16 and 77-78. The elected SEQ ID NO: 34 exhibits >80% sequence identity to SEQ ID NO: 15 of copending Application No. ‘156, wherein the G and S are missing at positions 1 and 2 of the N-terminus, respectively, and the C-terminus culminates with “AA”, thus meeting the limitations of the instant claims 1-5, 7-8, and 16-18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8, and 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, and 12 of copending Application No. 18/492,484 (‘484 reference application, claim set filed 7/31/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘484 recites a recombinant protein comprising (1) a first binding agent that specifically binds to a protein expressed on the surface of an immune cell; and (2) at least two second binding agents that specifically bind to at least two different tumor-associated antigens, wherein one of said second binding agents specifically binds to CD33 and comprise an amino acid sequence that is at least 85% identical to any one of SEQ ID NO: 15, 67 to 70, 111, and 112, wherein another said second binding agent specifically binds to CD123 and comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NO: 6, 65, 66, and 102-106, wherein any sequence variability within the at least two second binding agents occurs in non-randomized and/or framework amino acid positions, and wherein said at least two second binding agents are designed ankyrin repeat domains. Dependent claims 11 and 12 further specify that the recombinant protein of claim 1 is at least 80% identical to any one of SEQ ID NO: 11-14, 79-80, 84-86, and 96-101 (claim 11) or 95-100 (claim 12). The SEQ ID NO: 96 has only four substitutions relative to SEQ ID NO: 100 of copending Application No. ‘484, thus meeting the limitations of the instant claims 1-2, 8, and 16-18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8, 10, 11, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 20, 21, and 23 of copending Application No. 19/156,043 (‘043 reference application, claim set filed 8/13/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘043 recites a designed ankyrin repeat domain for use in reducing accumulation of a therapeutic and/or diagnostic agent in the kidney of a subject treated with said agent, wherein the designed ankyrin repeat domain is administered to the subject in an amount effective to reduce accumulation of said therapeutic and/or diagnostic agent in the kidney. Dependent claim 12 further recites the designed ankyrin repeat domain for use according to claim 1, wherein the designed ankyrin repeat domain comprises an amino acid sequence selected from the group consisting of (1) SEQ ID NO: 1 and (2) sequences with at least 80% amino acid sequence identity with SEQ ID NO: 1. The instant SEQ ID NO: 94 and 96 each has 4 substitutions relative to SEQ ID NO: 1 of copending Application No. ‘043. The instant specification teaches that peptides of the invention can be administered to a mammal (Pg 4, lines 13-15). Thus, claims 1-2, 8, and 16-18 are anticipated.
Dependent claims include an isolated nucleic acid or recombinant vector of the peptide (claims 20 and 21) and a pharmaceutical composition thereof (claim 23).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-11, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 14, and 16-18 of copending Application No. 18/719,008 (‘008 reference application, claim set filed 6/12/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 9 of copending Application No. ‘008 recites a designed repeat domain having a first binding specificity for a first target and a second binding specificity for a second target, wherein binding of said designed repeat domain to said first and second targets is mutually exclusive. Dependent claim 14 further recites the designed repeat domain of claim 9, wherein said designed repeat domain comprises (i) an N-terminal capping module comprising a sequence selected from the group consisting of (1) SEQ ID NOs: 35, 36, 47 to 63, 83 to 85 and 97 to 100 and (2) sequences in which up to 9 amino acids in any of SEQ ID NOs: 35, 36, 47, 53, 59, 60, 83 and 84 are substituted by another amino acid; and/or (ii) a C-terminal capping module comprising a sequence selected from the group consisting of (1) SEQ ID NOs: 37, 38 and 64 to 74 and (2) sequences in which up to 9 amino acids in any of SEQ ID NOs: 37, 38 and 69 are substituted by another amino acid, and/or (iii) at least one internal repeat module comprising a sequence selected from the group consisting of (1) SEQ ID NOs: 40 to 46 and (2) sequences in which up to 9 amino acids in any of SEQ ID NOs: 40 to 46 are substituted by another amino acid. The instant SEQ ID NO: 95 has 4 substitutions relative to SEQ ID NO: 45 of copending Application No. ‘008, thus meeting the limitations of the instant claims 1-2, 8, and 16-18.
Dependent claims further include the addition of a therapeutic agent (claim 16), a nucleic acid molecule encoding the protein (claim 17), and a pharmaceutical composition thereof (claim 18).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 8- 11, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4, 14, and 19-20 of copending Application No. 18/554,248 (‘248 reference application, claim set filed 1/22/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 2 of copending Application No. ‘248 recites a recombinant binding protein comprising an ankyrin repeat domain, wherein said ankyrin repeat domain has binding specificity for human CD70, and wherein said ankyrin repeat domain comprises an amino acid sequence with at least 85% amino acid sequence identity with any one of SEQ ID NOs: 1 to 12 and 71 to 72. The instant SEQ ID NO: 96 has 4 or fewer substitutions relative to SEQ ID NO: 12 and 72 of copending Application No. ‘248, thus meeting the limitations of the instant claims 1-2, 8, and 16-18.
Dependent claims further recite functional characteristics of the recombinant binding protein of claim 2 (claims 3 and 4), the addition of a moiety to extend half-life (claim 14), a nucleic acid encoding the protein (claim 19), and a pharmaceutical composition comprising the protein or nucleic acid and a carrier or diluent (claim 20).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-11, and 16-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 10, and 14-16 of copending Application No. 17/925,138 (‘138 reference application, claim set filed 8/7/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Claim 1 of copending Application No. ‘138 recites a recombinant binding protein comprising an ankyrin repeat domain, wherein said ankyrin repeat domain has binding specificity for CD40, and wherein said ankyrin repeat domain comprises an ankyrin repeat module comprising an amino acid sequence selected from the group consisting of (1) SEQ ID NOs: 39 to 95 and (2) sequences in which up to 10 amino acids in any of SEQ ID NOs: 39 to 95 are substituted by other amino acids. The instant SEQ ID NO: 94 has 2 or fewer substitutions relative to SEQ ID NO: 50 and 53 of copending Application No. ‘248, and the instant SEQ ID NO: 96 has 3 mutations relative to SEQ ID NO: 67 of copending Application No. ‘248. Thus the limitations of the instant claims 1-2, 8, and 16-18 are met.
Claim 7 of copending Application No ‘138 recites a recomb