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 Claims
Claims 1-2, 4, 7-9, 13-14, 17-20, and 22-31 are currently pending.
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 FRαmework for Patent Electronic System (https://www.uspto.gov/PatentLegalFRαmework), hereinafter "Legal FRαmework") 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 - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in Fig. 46 and labelled “3-66*01.”
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Drawings
The drawings are objected to because “SEQ ID No.” shown in Figure 12 should be “SEQ ID NO:”. Figure 46 does not contain a corresponding SEQ ID NO: for each sequence in the drawings or specification. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the description of Fig. 46 (see ¶ [0063] on pg. 10) does not disclose the SEQ ID NO: for each sequence shown.
Appropriate correction is required.
Claim Interpretation
The scope of antibody constructs comprising a “first folate receptor alpha (FRα) antigen-binding domain” is interpreted as requiring “one or more” FRα binding domains. That is, at least one FRα binding domain is required, but additional binding domains may be present. Thus, the use of the term “first” is not interpreted as indicating that an additional binding domain is necessarily present.
Claim Objections
37 CFR 1.71(a) requires the claims to be written in “full, clear, concise, and exact terms.” Claims 1, 7, 8, 9, 13, 14, 23, and 24 are objected to because of the following informalities: Claims 1, 8, 9, 13, 14, 23, and 24 are inconsistent with spacing between “SEQ ID NO:” and the numerical identity. For example, instant claim 1 recites “SEQ ID NO: 499” but claim 14 recites SEQ ID NO:46[.]” While either format may be appropriate, the claim set should be internally consistent with punctuation.
Claim 7 in line 8 lacks a comma at the end of part e).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4, 7-9, 13-14, 17-20, and 22-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a VH, HCDR1, HCDR2, HCDR3, VL, LCDR1, LCDR2, and LCDR3 comprising “the sequence as set forth in” SEQ ID NO: X. Infringing activity on a sequence “as set forth in” would be unclear because some skilled artisans would argue that “the sequence as set forth in” includes reference to fragments of the sequence of, e.g. SEQ ID NO: 498. Claims 8, 9, 13, 14, 23, and 24 also recite “the sequence as set forth in” and are indefinite for the same reasons.
For the purpose of searching and examination, the claim limitations are interpreted as “comprising / comprises SEQ ID NO:” or “having at least 85%... sequence identity to SEQ ID NO:”. In other words, the instant claims are interpreted as requiring all amino acids of the sequences consistent with the scope of the claims and excluding fragments of the recited sequences.
Claim one is further unclear on the grounds that it would be unclear to the skilled artisan whether the limitations of the first “wherein” clause in lines 17-19 only apply to the framework regions or whether said modifications may additionally occur in the CDRs. The scope of lines 5-16 clearly limit the FRα binding domain to a binding domain comprising particularly defined CDR sequences. Insofar as lines 17-19 recite the FRα “further comprises one or more amino acid modifications” in the VH or VL, some skilled artisan would argue that said amino acid modifications may only occur in the framework regions because the structure has been limited to specific CDRs. However, other skilled artisan would argue that the scope of “further comprises” encompasses modifications to the amino acids of the recited CDR sequences. Noted herein, if Applicant intends the latter interpretation, claim 1 and those dependent thereon are subject to a rejection under 35 U.S.C. 112(a) for a lack of written description as set forth below.
For the purpose of searching and applying art, the claim is construed as having any modifications in the VH and VL, excluding the CDRs. In other words, the claim is interpreted as being limited to the sequences of the CDRs recited in lines 5-16.
Claims 2, 4, 7, 17, 18, 19, 20, 22, and 25-31 are rejected by virtue of their dependency.
Claim 18 recites a number of Fc mutation such as “T350V_L351Y_F405A_Y407V,” which renders the claims indefinite because it would be unclear to the skilled artisan whether infringement occurs only with an Fc polypeptide comprising all mutations joined by an underscore. Some skilled artisan would argue that the use of the underscore indicates that all mutations are required, while other skilled artisan would argue that it is unclear whether the mutations include optional embodiments. For example, does an Fc polypeptide comprising “T350V_L351Y_F405A_Y407V” have the scope of an Fc polypeptide comprising “T350V, L351, F405A, and Y407” or “T350V, L351, F405A, and/or Y407”?
To advance prosecution on the merits, claim 18 is interpreted as require at least one of the mutations recited in a grouping joined by an underscore. E.g. an Fc polypeptide comprising “T350V_L351Y_F405A_Y407V” is interpreted as an Fc polypeptide comprising “at least one of T350V, L351Y, F405A, and Y407V.”
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4, 7, 8, 14, 24, and 26 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Insofar as claim 1 in lines 17-19 may be interpreted as not including modifications to the recited CDR sequences, the following applies to claims 4 and 7: Claims 4 and 7 recite substitutions at position I53 according to Kabat in the VH of claim 8, SEQ ID NO: 310. I53 according to Kabat of SEQ ID NO: 310 is amino acid 6 of HCDR2 according to SEQ ID NO: 499. Claim 1 is limited to an anti-FRα binding domain comprising an HCDR2 of SEQ ID NO: 499, which is interpreted as being limited to the recited amino acid sequence with any residues N- and/or C-terminal. Therefore, reciting a substitution at position I53 broadens the scope of the anti-FRα binding domain recited in claim 1.
Claim 8 recites an antibody construct of claim 7 comprising a VH comprising SEQ ID NO: 310 and a VL comprising SEQ ID NO: 315, however neither SEQ ID NO: 310 nor SEQ ID NO: 315 have any mutation listed in claim 7.
Claim 24 is directed to the antibody construct of claim 23 having two light chain polypeptide sequences comprising SEQ ID NO: 855. SEQ ID NO: 855 has a VL according to SEQ ID NO: 58 (as shown in the alignment below).
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However, claim 23 limits both 4-1BB binding domains to VL according to SEQ ID NO: 54. Therefore, claim 24 broadens the scope of instant claim 23.
Claim 26 does not further limit the scope of the antibody construct of claim 1 because the preamble of “a pharmaceutical composition” is necessarily a characteristic of the antibody construct and no additional limitations, e.g. a pharmaceutically acceptable excipient, are required by the claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 2, 4, 7, 13, 14, 17-20, 22, and 25-31 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.
Insofar as one may interpret claim 1 in lines 17-19 as including modifications to the CDR sequences recited in lines 5-16, the following applies to claim 1: The scope of claim 1, under some interpretations (see rejection under 35 U.S.C. 112(b) above), includes “one or more amino acid modifications” to the CDR sequences that improve biophysical properties of the antibody construct. “Amino acid” is interpreted as any “naturally occurring and non-naturally occurring amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids.” (see specification on pg. 104 in ¶ [00347]). Noted herein, the scope of “one or modifications” includes any substitution, deletion, insertions, post-translational modification, to an existing amino acid and including insertion and substitutions with non-naturally occurring amino acids, analogs, and mimetics. Indeed, in view of the breadth of structures claimed, any and all amino acid residues in the CDRs may be completely altered with respect to the recited SEQ ID NOs.
Claim 14, regardless of the interpretation of claim 1, additionally lacks a written description. Claim 14b) recites a 4-1BB antigen binding site having a VH with at least 90% sequence identity to SEQ ID NO: 62 and a VL with at least 90% sequence identity to SEQ ID NO: 64. SEQ ID NOs: 62 and 64 relate to humanized clone 5G8 (see specification on pg. 241-242). All VL variants of humanized 5G8 comprise an LCDR2 of RASQNVGTNVA. However, claim 13, from which claim 14 depends does not recite a SEQ ID NO: having RASGNVGTNVA for LCDR2. The closest embodiment recited in claim 13b) comprises an LCDR2 of SEQ ID NO: 550, which is KASQNVGTNVA. The unmodified light chain of 5G8, SEQ ID NO: 36 (see specification on pg. 240) comprises KASQNVGTNVA, however SEQ ID NO: 36 is not 90% identical to SEQ ID NO: 64. In summary, claim 14b) is directed to an antigen binding site that binds to 4-1BB, comprises a combination of CDRs recited in claim 13, and has a VL 90% identical to SEQ ID NO: 64 which does not comprise an LCDR2 recited in claim 13.
Claim 23 recites a 4-1BB binding site comprising SEQ ID NO: 46 and SEQ ID NO: 54. SEQ ID NO: 46 relates the VH of humanized clone 1G1 and SEQ ID NO: 54 relates to the VL of humanized clone 1C8 (see pg. 241 of the specification).
MPEP § 2163 states:
"The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice ... reduction to drawings ... or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. In unpredictable arts a widely variant genus cannot be represented by only one species. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Furthermore, establishment of a ‘reasonable structure-function correlation’ can also describe a genus and may be established ‘by the inventor as described in the specification,’ or ‘known in the art at the time of the filling date.’ See MPEP 2163 (II)(A)(3)(a)(ii) and Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’)."
Regarding claim 1
Applicants disclose at least 22 variants of 8K22, the FRα clone to which the instantly claimed sequences pertain. (see specification at pg. 207 in Table 32). However, only 6 of said variants comprise a modification in a CDR sequence, I53S or I53D in clones 31591, 31592, 31602, 31603, 31604, and 31605. The skilled artisan would not have determined 6 species as being representative of the genus of FRα antigen-binding encompassing any and/or all amino acids of the CDRs of 8K22 being altered. No additional species within the scope of this genus were found in the prior art.
Regarding claims 14b) and 23
The specification discloses 3 anti-4-1BB VL sequences that are within 90% sequence identity to SEQ ID NO: 64, SEQ ID NOs: 65, 66, and 50 (see attached VL sequence alignment). However, none comprise any LCDR2 recited in instant claim 14. All sequences that are 90% identical to other VL sequences recited in claim 14, SEQ ID NO: 58 (at least 90% identical to SEQ ID NOs: 60, 59 and 49) or SEQ ID NO: 48 (at least 90% identical to SEQ ID NOs: 55 and 54), do not comprise an LCDR2 of SEQ ID NO: 550. Therefore, the specification does not disclose any species having 90% sequence identity to SEQ ID NO: 64 having the LCDRs recited in instant claim 13. The instant specification does not disclose any species having the VH of clone 1G1 and the VL of clone 1C8. Similarly, no species within this scope were found in the prior art.
The art is highly unpredictable in respect to correlations between the structure and binding properties of CDRs.
Rudikoff et al. found that a single amino acid change in a CDR completely altered antigen-binding specificity (Rudikoff et al. Proc Natl Acad Sci. 1982. 79: 1979-1983; cited herewith, pg. 1982, left column, second full paragraph). Bedouelle et al. (FEES J. 2006 Jan;273(1):34-46; cited herewith) examined the effects of alanine substitutions on each of the residues of the antibody heavy and light chain CDR3 regions and showed mutation of certain residues cause a > 100 fold drop in the “off rate” for ligand dissociation (Bedouelle et al., pg. 38-39; see Table 2). Bedouelle suggests that some mutations had a direct effect on antigen binding while others indirectly affect the conformation of the antigen binding site, thereby indirectly affecting antigen binding (see Discussion Section). This illustrates the unpredictability of making mutations within the CDRs of an antibody, especially the CDR3 domains. Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28; cited herewith) teaches that antigen binding is resultant from the 6 CDRs, or hypervariable regions, the variable region of an antibody (see, page 416, column bridging paragraph, emphasis added). Vajdos used a shotgun scanning mutagenesis using phage displayed libraries of protein mutants, which required extensive experimentation to comprehensively scan the potential CDR sequence space (see page 416, right column, 2nd paragraph and pages 425-427, Materials and Methods). Furthermore, even after performing this comprehensive scanning mutagenesis of all CDR residues from the particular anti-ErB2 antibody, Vajdos would still not have been able to say which CDR residues were actually involved in antigen binding, and which were involved in stabilizing the secondary and tertiary structure of the CDRs within the context of the heavy and light chains as a whole, without the structure of the unbound antigen-binding site of the antibody to aid in their analysis (see, in particular, Discussion, pages 422- 425). Rather, Vajdos needed to perform not only a comprehensive shotgun scanning mutagenesis of all CDR residues of the antibody under study, but also needed a structure of the unbound antigen binding site in hand to gain a sufficient understanding of the contribution of each CDR to antigen-binding to adequately predict which CDR residues can be changed, and to what extent, or in what context of additional compensatory mutations in other regions of the antibody.
Collectively, Rudikoff et al. Bedouelle et al., and Vajdos et al. demonstrate the amino acids of a CDR that are responsible for binding with a particular antigen cannot be determined by observation of the amino acid sequence alone. Indeed, Vajdos et al. showed it required the epitope of the antigen as well. Additionally, the ability to bind to a particular antigen is extremely sensitive to changes in CDR sequences.
"A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
Regarding claim 14b)
While a single substitution of R24K, according to Kabat, in SEQ ID NO: 64 would be within the scope of the genus of antibody described as having 90% identity to SEQ ID NO: 64 and having the CDRs recited in claim 13, the art indicates that a skilled artisan would not have been able to predict whether such a substitution would retain the property of binding to 4-1BB. Indeed, in view of the fact that all known species within 90% identity to SEQ ID NO: 64 have an arginine at position 24, one may infer that this amino acid may be required for each species within the genus to bind to 4-1BB. Similarly, one of ordinary skill would not be able to predict whether combining the VH of one clone, i.e. clone 1G1, with the VL of another clone, i.e. clone 1C8, would result in the claimed property of binding 4-1BB.
Regarding claim 1
In addition to the unpredictability with respect to the functional effects of modifying any one amino acid within a CDR, the art also indicates that antibodies binding to the same target can have highly diverse structural features on account of their CDR sequences. For example, Edwards et al. (J Mol Biol. 2003. 334: 103–118, cited herewith) generated over 1000 antibodies with 568 unique CDR3s identified, all against that same target, the B-lymphocyte growth factor known as “BLyS”, wherein 500 antibodies inhibited BLyS activity (see Abstract). Thus, the scope of antibodies binding to FRα, having improved biophysical properties, and having modifications in any or all amino acids of the CDRs recited in claim 1 is extremely broad. Indeed, the person of ordinary skill would not have determined 6 clones as being representative of such a breadth of structures. Moreover, in view of the unpredictability of the art and limited structures disclosed, one of skill would not have been able to determine any structure-function correlation between an antibody having modifications in any or all amino acids of the CDRs recited in claim 1 and the functions of binding to FRα and having improved biophysical properties.
In conclusion, there are no representative species in the art and the species disclosed in the specification are not sufficient to represent the full breadth of antibodies binding to FRα, having improved biophysical properties, and having any amino acid modification in the CDRs of claim 1; an antibody that binds to 4-1BB having the VH of clone 1G1 and the VL of clone 1C8; and the full breadth of antibodies binding to 4-1BB and having a combination of CDRs recited in claim 13 and having a VL with 90% sequence identity to SEQ ID NO: 64. Furthermore, a structure-function correlation is not shown in the specification or the art to account for the high degree of variability of the CDRs as laid forth in the instant claims 1 and 14b). Thus claims 1 and 14 are rejected under of 35 U.S.C. 112(a) for failing to comply with the written description requirement. Claims 2, 4, 7, 13, 17-20, 22, and 25-31 are rejected by virtue of their dependency on claim 1.
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, 7-8, 13-14, 17-20, 22, and 25-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 10, 16-18, 22-24, 31-40, 44, 84, and 87-93 of copending Application No. 17/226,834 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because in view of claims 10, 18n), ‘834 recites an antibody construct as in instant claims 1, 2, 4, 7, 8, 22, and 26. Specifically, claim 18n) recites that the construct comprises an anti-FRα antigen binding domain comprising a sequence at least 85% identical to SEQ ID NO: 310 and 315, which are 100% identical to instant SEQ ID NO: 310 and 315. While ‘834 does not positively recite a modification that improves a biophysical property, this limitation is interpreted as being necessarily regarded as present by Applicants in SEQ ID NOs: 310 and 315 by virtue of claim 8’s dependency on claims 1 and 7. Additionally, while the instant claims do not recite the “first” anti-FRα binding domain of ‘834, the scope of the instant claims is broad enough to encompass an additional anti-FRα binding site wherein the label of “first” is arbitrary and does not confer a meaningful structural difference over the antibody construct of ‘834. In claim 32, ‘834 teaches a construct having the 4-1BB antigen binding site according to instant claims 13a) and 14a). ‘834 claims 22-24 teaches the Fc heterodimeric construct as in instant claims 17-19. ‘834 claim 33 teaches an antibody construct comprising an Fc region comprising the amino acid modifications of instant claim 20. ‘834 claim 34 teaches the antibody construct conjugated to a drug, relating to instant claim 25. ‘834 claims 36-38 teach nucleic acids, vectors, and isolated cell relating to instant claims 27-29. ‘834 claims 39-40 teach methods of preparing the antibody and treating a subject relating to instant claims 30-31.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
The anti-FRα antigen binding site recited in claim is considered free of the prior art. The closest prior art made of record is WO 2018/156740 A1 as cited in the IDS. ‘740 teaches a bispecific construct comprising an anti-4-1BB binding domain and an anti-FRα binding domain, however ‘740 does not teach an anti-FRα binding site having the instantly claimed combination of CDR sequences.
Conclusion
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/B.K.S./Examiner, Art Unit 1644
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683