DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicant’s response received August 13, 2026 is acknowledged.
Claims 12-21, 23, 25, and 26 have been canceled.
Claims 1-11, 22, 24, and 27-30 are pending in the instant application.
Applicant’s election without traverse of the invention of group I, drawn to antibody drug conjugated (ADC) that bind tissue factor (TF), presently claims 1-11, in the reply filed on August 13, 2024 is acknowledged.
Claims 22, 24, and 27-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 2, 2023.
Claims 1-11 are under examination in this office action.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
One important change in ST.26 as compared to ST.25 is the fact that polypeptide sequences shorter than four non-degenerate residues can no longer be identified via the use of a SEQ ID number. The instant application is the most recent child in a long lineage, and it is the filing date rather than the priority date which determines if an application must conform to ST.25 or ST.26. The filing date for the instant application is 12/1/2023 which makes it an ST.26 application, and the electronic sequence listing present in the instant application conforms to the rules of ST.26. Most specifically, as originally set forth in international application PCT/EP2011/059917 applicant chose to identify CDR sequences only three residues in length via SEQ ID number which was permissible, if discouraged, under ST.25. Applicant has not presented such short sequences in the electronic sequence listing (i.e. they are ”skipped” sequences as no data is present/it is blank/undefined) but such identifiers are still used in the specification and the claims (see for example SEQ ID NOs:47, 75, 79, and 43 in independent claim 1). ST.26 applies to the entire application, not just the sequence listing and thus it is impermissible to refer to amino acid sequences shorter than 4 residues anywhere in the application which includes the specification and the claims. Appropriate amendment to write in the appropriate sequences everywhere the “skipped” SEQ ID numbers occur is required. For example, part (i) of claim 1 cannot recite “SEQ ID NO:47” and instead must recite “a CDR2 region having the amino acid sequence AAS”. Similar correction for “skipped” sequences must be made in all claims and in all occurrences in the specification as submitted 12/1/2023.
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 and 4 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.
Regarding claims 1 and 4, the phrase "such as" render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Removal of the phrase “such as” is very strongly suggested.
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 and 3-11 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.
Applicant has broadly claimed antibody-drug conjugates (ADC) that bind to tissue factor (TF) wherein the drug is auristatin or an auristatin derivative. In independent claim 1, the antibody portion of the claimed product is defined by six specific, non-degenerate CDR sequences identified by SEQ ID number in parts (i) to (iii), while part (iv) recites “variants” which “preferably” have at most 1-3 modification, such as conservative substitutions. Notably, such exemplification (i.e. “preferably”, "such as”) fails to limit either the total number or types of “modifications” present in the recited “variants” that bind TF. To support such claims, the specification discloses the synthesis and cloning of multiple anti-TF antibodies from transgenic mice containing human Ig loci (see particularly examples 6 and 10) as well as conjugation to auristatins (example 16). No data concerning mutagenesis of lead clones, site directed or otherwise, appears to be disclosed in the specification as filed.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by 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 genus. See MPEP 2163. In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002). Recent court cases have emphasized the need for correlation between a well-defined structure and recited functional limitations. For example, the courts have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. As such, knowledge of where an antibody binds provides no information as to what such an antibody necessarily looks like (i.e. its primary amino acid structure). Applicant is reminded that the courts have long ruled that “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. As such, disclosure of a screening assay to test for functional properties of an antibody (such as its ability to bind TF) does not provide evidence of possession of the antibody itself.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway et al., see entire selection). It is also known that single amino acid changes in a CDR can abrogate the antigen binding function of an antibody (Rudikoff et al., see entire document, particularly the abstract and the middle of the left column of page 1982). Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves. In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), the following is noted. To show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Further, an adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). Indeed, the courts have long ruled that “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005). Also, “A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69. It should also be noted that the USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. This Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies and states: “In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”. Further, the courts have indicated that the enablement and written description requirements of 35 USC 112 are separable as can be seen in for example Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111.
Artisans are well aware that knowledge of a given antigen (for instance human TF) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al. teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al. disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document). Further, it should be noted that degenerate binding of the same structural motif by antibodies does not require the existence of sequence homology or identity at any of their CDRs or other chemical similarities at the antigen-binding sites; side chain mobility of epitope residues can confer steric and electrostatic complementarity to differently shaped combining sites, allowing functional mimicry to occur (Lescar et al., see entire document, in particular Abstract and Discussion). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen. Indeed, Kanyavuz et al. teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 1026 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 × 1014).
As discussed above, while parts (i)-(iii) define the antibody portion of the claimed ADC with sufficient structure that artisans would reasonably be assured that the recited functional properties would be present, par (iv) claims “variants” which as presently recited have zero structural limits as phrases including “preferably” and “such as” make it clear that the accompanying words are exemplification rather than limitation. As taught by Edwards et al., Lloyd et al., Lescar et al., and Goel et al., the number of potential antibody structures (i.e. sequences) which can bind to the same antigen is literally astronomical and as such those generated by applicant in transgenic humanized mice do not reasonably appear to be representative of such breadth. Note that, for the sake of argument, even if such words were removed that the “variant” must contain 1, 2, or 3 conservative substitution mutations (note if no mutations are present it isn’t reasonably a “variant”), problems would still be present. It would not be clear if the substitution mutations were limited to 3 total over all six CDRs or if each CDR could have 3 mutations, for a grand total of 18 mutations. In either case, such claims would show clear intent to alter the very structure generally accepted by artisans as being required for maintenance of functional activity. Given that as taught by Rudikoff et al. even a single CDR substitution can abrogate binding and applicant has not disclosed mutagenesis data concerning the 098, 111, and 114 clones (i.e. the antibodies from which the CDRs recited in parts (i) to (iii) of claim 1 were obtained, see in particular the table spanning pages 69-72 at the end of example 10) it does not appear reasonable that artisans would believe that random mutagenesis within the CDR sequences is commensurate with maintenance of the function of antigen binding.
Therefore, in view of the breadth of the claims artisans would reasonably conclude that applicant was not in possession of the full breadth of anti-TF antibodies as presently recited at the time the instant application was filed. Logically, if applicant was not in possession of the antibody portion, then applicant was also not in possession of the full breadth of claimed ADC constructs. Amendment of the claims to require that the antibody portion of the claimed ADC have six CDRs of fully defined sequence is one possible approach to obviating the issues discussed above.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Verploegen et al (WO2010/066803) in view of Doronina et al.
Verploegen et al. disclose anti-tissue factor (TF) antibodies which comprise the same sequences as those recited by SEQ ID number in the instant claims (see entire document, particularly figure 1 and the enclosed sequence alignments). Such antibodies are disclosed for use in the treatment of cancer, and as being conjugated to various cytotoxic moieties (see particularly pages 37 and 40-41). The places where such conjugated moieties are attached to the anti-TF antibodies include internal residues or sugars, including sulfhydryl residues (pages 37-41, most particularly pages 37 and 40). The constant domain of such antibodies is disclosed as being IgG1 (see particularly page 34). These teachings differ from the instant claimed invention in that auristatin is not disclosed as a drug which is conjugated to the anti-TF antibodies of Verploegen et al.
Doronina et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the title and abstract). Notably, they disclose that antibody conjugates comprising monomethylauristatin E (MMAE) with a valine citrulline linker were the most stable in buffer and plasma, and that such conjugates were the most effective in in vivo tumor models (see particularly the abstract as well as Figures 1, 3 and 5). Methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly Figure 1 and the Results subsection titles Preparation of mAb-auristatin conjugates, most particularly the top of the right column of page 779).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE to the anti-TF antibodies of Verploegen et al. in order to gain the advantages of increased efficacy and stability as compared to other drug-antibody conjugates as disclosed by Doronina et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Doronina et al. which describe the successful synthesis and use of antibody-MMAE conjugates.
Applicant is reminded that affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of prior applications do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Claims 1-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Verploegen et al (WO2010/066803) in view of Dennis et al. (US2009/0280056).
Verploegen et al. disclose anti-tissue factor (TF) antibodies which comprise the same sequences as those recited by SEQ ID number in the instant claims (see entire document, particularly figure 1 and the enclosed sequence alignments). Such antibodies are disclosed for use in the treatment of cancer, and as being conjugated to various cytotoxic moieties (see particularly pages 37 and 40-41). The places where such conjugated moieties are attached to the anti-TF antibodies include internal residues or sugars, including sulfhydryl residues (pages 37-41, most particularly pages 37 and 40). The constant domain of such antibodies is disclosed as being IgG1 (see particularly page 34). These teachings differ from the instant claimed invention in that auristatin is not disclosed as a drug which is conjugated to the anti-TF antibodies of Verploegen et al.
Dennis et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, examples 3-8, and claim 130). It should be noted that such Ab-drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly paragraphs [0080-0086], [0546-0587] and examples 3 and 6). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly examples 5 and 6). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (see particularly examples 4 and 8).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti-TF antibodies of Verploegen et al. in order to gain the advantages of high killing efficacy as disclosed by Dennis et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Dennis et al. which describe the successful synthesis and use of antibody-auristatin conjugates.
Applicant is reminded that affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of prior applications do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Claims 1-11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Verploegen et al (WO2010/066803) in view of US Patent 7,498,298.
Verploegen et al. disclose anti-tissue factor (TF) antibodies which comprise the same sequences as those recited by SEQ ID number in the instant claims (see entire document, particularly figure 1 and the enclosed sequence alignments). Such antibodies are disclosed for use in the treatment of cancer, and as being conjugated to various cytotoxic moieties (see particularly pages 37 and 40-41). The places where such conjugated moieties are attached to the anti-TF antibodies include internal residues or sugars, including sulfhydryl residues (pages 37-41, most particularly pages 37 and 40). The constant domain of such antibodies is disclosed as being IgG1 (see particularly page 34). These teachings differ from the instant claimed invention in that auristatin is not disclosed as a drug which is conjugated to the anti-TF antibodies of Verploegen et al.
The ‘298 patent discloses methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, sections 4.5-4.8.7, examples 1-33, and claims 1-22). It should be noted that such Ab-drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly tables 2a-2d and examples 24-33). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (ibid). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (ibid).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti-TF antibodies of Verploegen et al. in order to gain the advantages of high killing efficacy as disclosed by the ‘298 patent. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of the ‘298 patent which describe the successful synthesis and use of antibody-auristatin conjugates.
Applicant is reminded that affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of prior applications do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1 and 3-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No. 9,150,658 in view of Doronina et al.
The issued claims recite antibodies which bind TF and their administration to treat cancer. Such antibodies are recited generically as “competing” for binding to TF with a named antibody as well as being specifically defined as comprising specific SEQ ID numbers to define structural elements. For example, issued claim 22 recites antibodies which bind TF and which have fully defined VH and VL sequences identified by SEQ ID numbers. Such antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 41) and cancer specifically (issued claim 42). The antibodies used in such methods can be conjugated to additional moieties (issued claim 29) or present in pharmaceutical compositions with additional therapeutic agents (issued claim 43). Anti-TF antibodies of the IgG1 isotype are also claimed (see issued claim 33 in particular). It is noted that the antibodies of exact sequence recited in the issued claims differ from the fully defined sequences recited in the instant claims (see for example instant claim 2 which is not part of this rejection). However, the broadest issued claims are not defined as having any particular sequence, and notably part (iv) of instant independent claim 1 as amended 6/2/23 recites sequence variants wherein the sequences to be mutated are the CDRs. Notably, the instant claims recite that the variant “preferably” has at most 1, 2, or 3 “modification”, but such exemplification is non-limiting as “preferably” is not equivalent to “must have”. Therefore, part (iv) of instant claim 1 reads upon antibodies of any CDR sequence (e.g. no amino acid residue has to match anywhere) so long as they have the recited functional property of binding to tissue factor. In view of this, the sequences of the anti-TF antibodies of the issued claims and those presently recited are equivalent. The instant claims differ from the issued claims in that the issued claims do not recite explicitly antibody drug conjugates or their method of manufacture.
Doronina et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the title and abstract). Notably, they disclose that antibody conjugates comprising monomethylauristatin E (MMAE) with a valine citrulline linker were the most stable in buffer and plasma, and that such conjugates were the most effective in in vivo tumor models (see particularly the abstract as well as Figures 1,3 and 5). Methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly Figure 1 and the Results subsection titles Preparation of mAb-auristatin conjugates, most particularly the top of the right column of page 779).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE to the anti-TF antibodies used in the compositions and methods of treating cancer recited in the issued claims of the ‘658 patent. The ordinary artisan would have been motivated to do so in order to gain the advantages of increased efficacy and stability as compared to other drug-antibody conjugates as disclosed by Doronina et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Doronina et al. which describe the successful synthesis and use of antibody-MMAE conjugates, and because the use of anti-TF antibodies tagged with cytotoxic drugs to treat cancer is well-known in the prior art.
Claims 1 and 3-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims over claims 1-43 of U.S. Patent No. 9,150,658 in view of Dennis et al. (US2009/0280056).
The issued claims recite antibodies which bind TF and their administration to treat cancer. Such antibodies are recited generically as “competing” for binding to TF with a named antibody as well as being specifically defined as comprising specific SEQ ID numbers to define structural elements. For example, issued claim 22 recites antibodies which bind TF and which have fully defined VH and VL sequences identified by SEQ ID numbers. Such antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 41) and cancer specifically (issued claim 42). The antibodies used in such methods can be conjugated to additional moieties (issued claim 29) or present in pharmaceutical compositions with additional therapeutic agents (issued claim 43). Anti-TF antibodies of the IgG1 isotype are also claimed (see issued claim 33 in particular). It is noted that the antibodies of exact sequence recited in the issued claims differ from the fully defined sequences recited in the instant claims (see for example instant claim 2 which is not part of this rejection). However, the broadest issued claims are not defined as having any particular sequence, and notably part (iv) of instant independent claim 1 as amended 6/2/23 recites sequence variants wherein the sequences to be mutated are the CDRs. Notably, the instant claims recite that the variant “preferably” has at most 1, 2, or 3 “modification”, but such exemplification is non-limiting as “preferably” is not equivalent to “must have”. Therefore, part (iv) of instant claim 1 reads upon antibodies of any CDR sequence (e.g. no amino acid residue has to match anywhere) so long as they have the recited functional property of binding to tissue factor. In view of this, the sequences of the anti-TF antibodies of the issued claims and those presently recited are equivalent. The instant claims differ from the issued claims in that the issued claims do not recite explicitly antibody drug conjugates or their method of manufacture.
Dennis et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, examples 3-8, and claim 130). It should be noted that such Ab-drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly paragraphs [0080-0086], [0546-0587] and examples 3 and 6). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly examples 5 and 6). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (see particularly examples 4 and 8).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the cancer treatment methods of the ‘658 patent in order to gain the advantages of high killing efficacy as disclosed by Dennis et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Dennis et al. which describe the successful synthesis and use of antibody-auristatin conjugates and the long history of using anti-TF-cytotoxic drug conjugates for treating cancer in the prior art.
Claims 1 and 3-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No. 9,150,658 in view of US Patent 7,498,298.
The issued claims recite antibodies which bind TF and their administration to treat cancer. Such antibodies are recited generically as “competing” for binding to TF with a named antibody as well as being specifically defined as comprising specific SEQ ID numbers to define structural elements. For example, issued claim 22 recites antibodies which bind TF and which have fully defined VH and VL sequences identified by SEQ ID numbers. Such antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 41) and cancer specifically (issued claim 42). The antibodies used in such methods can be conjugated to additional moieties (issued claim 29) or present in pharmaceutical compositions with additional therapeutic agents (issued claim 43). Anti-TF antibodies of the IgG1 isotype are also claimed (see issued claim 33 in particular). It is noted that the antibodies of exact sequence recited in the issued claims differ from the fully defined sequences recited in the instant claims (see for example instant claim 2 which is not part of this rejection). However, the broadest issued claims are not defined as having any particular sequence, and notably part (iv) of instant independent claim 1 as amended 6/2/23 recites sequence variants wherein the sequences to be mutated are the CDRs. Notably, the instant claims recite that the variant “preferably” has at most 1, 2, or 3 “modification”, but such exemplification is non-limiting as “preferably” is not equivalent to “must have”. Therefore, part (iv) of instant claim 1 reads upon antibodies of any CDR sequence (e.g. no amino acid residue has to match anywhere) so long as they have the recited functional property of binding to tissue factor. In view of this, the sequences of the anti-TF antibodies of the issued claims and those presently recited are equivalent. The instant claims differ from the issued claims in that the issued claims do not recite explicitly antibody drug conjugates or their method of manufacture.
The '298 patent discloses methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, sections 4.5-4.8.7, examples 1-33, and claims 1-22). It should be noted that such Ab- drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly tables 2a-2d and examples 24-33). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (ibid). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (ibid).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the methods of the ‘658 patent in order to gain the advantages of high killing efficacy as disclosed by the '298 patent. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of the '298 patent which describe the successful synthesis and use of antibody-auristatin conjugates.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 9,714,297 in view of Doronina et al.
The issued claims recite antibodies which bind TF and their administration to treat cancer (see all claims, most particularly claims 27-29). Such antibodies are recited generically as competing for binding to TF with reference antibodies defined by SEQ ID numbers (see issued claim 1) and as comprising specific VH and VL sequences identified by SEQ ID number. The antibodies of the issued claims have the same sequences as those of the instant claimed invention. Specifically, instant SEQ ID NO:1 is SEQ ID NO:5 in the issued claim 3 and instant SEQ ID NO:41 is the same as SEQ ID NO:61 in issued claim 3, and these VH and VL have the same CDRs as what is recited in instant claim 1. The issued antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 27) and cancer specifically (issued claim 28). The antibodies used in such methods are present in pharmaceutical compositions with additional therapeutic agents (issued claim 29). Anti-TF antibodies of the IgG1 isotype are also recited (see issued claim 19 in particular). Given that the sequences of the anti-TF antibodies recited in the issued and copending claims are the same, the instant claims differ from the issued claims in that the issued claims do not explicitly recite antibody drug conjugates or methods of making such conjugates.
Doronina et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the title and abstract). Notably, they disclose that antibody conjugates comprising monomethylauristatin E (MMAE) with a valine citrulline linker were the most stable in buffer and plasma, and that such conjugates were the most effective in in vivo tumor models (see particularly the abstract as well as Figures 1,3 and 5). Methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly Figure 1 and the Results subsection titles Preparation of mAb-auristatin conjugates, most particularly the top of the right column of page 779).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE to the anti-TF antibodies used in the compositions and methods of treating cancer recited in the claims of the ‘297 patent. The ordinary artisan would have been motivated to do so in order to gain the advantages of increased efficacy and stability as compared to other drug-antibody conjugates as disclosed by Doronina et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Doronina et al. which describe the successful synthesis and use of antibody-MMAE conjugates, and because the use of anti-TF antibodies tagged with cytotoxic drugs to treat cancer is well-known in the prior art.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 9,714,297 in view of Dennis et al. (US2009/0280056).
The issued claims recite antibodies which bind TF and their administration to treat cancer (see all claims, most particularly claims 27-29). Such antibodies are recited generically as competing for binding to TF with reference antibodies defined by SEQ ID numbers (see issued claim 1) and as comprising specific VH and VL sequences identified by SEQ ID number. The antibodies of the issued claims have the same sequences as those of the instant claimed invention. Specifically, instant SEQ ID NO:1 is SEQ ID NO:5 in the issued claim 3 and instant SEQ ID NO:41 is the same as SEQ ID NO:61 in issued claim 3, and these VH and VL have the same CDRs as what is recited in instant claim 1. The issued antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 27) and cancer specifically (issued claim 28). The antibodies used in such methods are present in pharmaceutical compositions with additional therapeutic agents (issued claim 29). Anti-TF antibodies of the IgG1 isotype are also recited (see issued claim 19 in particular). Given that the sequences of the anti-TF antibodies recited in the issued and copending claims are the same, the instant claims differ from the issued claims in that the issued claims do not explicitly recite antibody drug conjugates or methods of making such conjugates.
Dennis et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, examples 3-8, and claim 130). It should be noted that such Ab-drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly paragraphs [0080-0086], [0546-0587] and examples 3 and 6). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly examples 5 and 6). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (see particularly examples 4 and 8).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the cancer treatment methods of the ‘297 patent in order to gain the advantages of high killing efficacy as disclosed by Dennis et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Dennis et al. which describe the successful synthesis and use of antibody-auristatin conjugates and the long history of using anti-TF-cytotoxic drug conjugates for treating cancer in the prior art.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 9,714,297 in view of US Patent 7,498,298.
The issued claims recite antibodies which bind TF and their administration to treat cancer (see all claims, most particularly claims 27-29). Such antibodies are recited generically as competing for binding to TF with reference antibodies defined by SEQ ID numbers (see issued claim 1) and as comprising specific VH and VL sequences identified by SEQ ID number. The antibodies of the issued claims have the same sequences as those of the instant claimed invention. Specifically, instant SEQ ID NO:1 is SEQ ID NO:5 in the issued claim 3 and instant SEQ ID NO:41 is the same as SEQ ID NO:61 in issued claim 3, and these VH and VL have the same CDRs as what is recited in instant claim 1. The issued antibodies are further claimed for use in methods of treating inhibiting growth and/or proliferation of tumor cells (issued claim 27) and cancer specifically (issued claim 28). The antibodies used in such methods are present in pharmaceutical compositions with additional therapeutic agents (issued claim 29). Anti-TF antibodies of the IgG1 isotype are also recited (see issued claim 19 in particular). Given that the sequences of the anti-TF antibodies recited in the issued and copending claims are the same, the instant claims differ from the issued claims in that the issued claims do not explicitly recite antibody drug conjugates or methods of making such conjugates.
The '298 patent discloses methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, sections 4.5-4.8.7, examples 1-33, and claims 1-22). It should be noted that such Ab- drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly tables 2a-2d and examples 24-33). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (ibid). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (ibid).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the methods of the ‘297 patent in order to gain the advantages of high killing efficacy as disclosed by the '298 patent. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of the '298 patent which describe the successful synthesis and use of antibody-auristatin conjugates.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,168,314.
The issued claims recite anti-TF/auristatin drug conjugates wherein the antibodies are defined by either six unique, non-degenerate CDR sequences or are defined by complete VH and VL sequences, all of which are identified by SEQ ID numbers. Notably, the SEQ ID numbers are identical between the ‘314 patent and the instant application (which is unsurprising as the application which became the ‘314 patent is the great-great-grandparent of the instant application). It should be pointed out that full length antibodies, monoclonal IgG1 antibodies, the use of MMAE and MMAF, and pharmaceutical compositions are all present in the ‘314 claims (see for example issued claims 3-10). Note also that the auristatin is recited as being conjugated to the antibody by a linker (see issued claim 1). Given that the sequences of the anti-TF antibodies recited in the issued and instant claims are the same, the issued claims anticipate what is presently claimed as the issued claims do not allow for undefined sequence variants/mutants as set forth in part (iv) of the instant independent claim.
Claims 1 and 3-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,617,764.
The issued claims recite anti-TF/auristatin drug conjugates wherein the antibodies are defined by either six unique, non-degenerate CDR sequences or are defined by complete VH and VL sequences, all of which are identified by SEQ ID numbers. Notably, while the sequences represented by the SEQ ID numbers in the issued and instant claims do not match, given the fact that the “variant” language of part (iv) in instant independent claim 1 allows for complete replacement of every CDR sequence, the sequences of the issued claims anticipate the breadth of what is presently claimed. It should be pointed out that full length antibodies as well as conjugation of the auristatin MMAE using a valine citrulline dipeptide linker are all present in the ‘764 claims (see for example issued claims 1 and 17).
Claims 1, 3, 5, and 7-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 67, 68, 70, 71, and 84-88 of copending Application No. 19/077,379 in view of Doronina et al.
It should be noted that the ‘379 application is the latest application in a long unbroken line of continuations and divisional going back to the international application which entered the US national phase and became US patent 9.150.658 discussed above, and thus all biological sequences are identical to those discussed supra concerning the ‘658 and ‘297 patents. The ‘379 application claims human antibodies that bind human TF and have CDRs that are identical to those positively recited by SEQ ID number in instant claim 1, as well as bispecific versions of such antibodies, nucleic acids, vectors, and methods of administering such antibodies to treat disease (see all copending claims, particularly copending claim 1). The copending claims differ from the instant claims in that the copending claims do not recite antibody drug conjugates such as those including MMAE or MMAF.
Doronina et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the title and abstract). Notably, they disclose that antibody conjugates comprising monomethylauristatin E (MMAE) with a valine citrulline linker were the most stable in buffer and plasma, and that such conjugates were the most effective in in vivo tumor models (see particularly the abstract as well as Figures 1,3 and 5). Methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly Figure 1 and the Results subsection titles Preparation of mAb-auristatin conjugates, most particularly the top of the right column of page 779).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE to the anti-TF antibodies used in the compositions and methods of treating cancer recited in the copending claims of the ‘379 application. The ordinary artisan would have been motivated to do so in order to gain the advantages of increased efficacy and stability as compared to other drug-antibody conjugates as disclosed by Doronina et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Doronina et al. which describe the successful synthesis and use of antibody-MMAE conjugates, and because the use of anti-TF antibodies tagged with cytotoxic drugs to treat cancer is well-known in the prior art.
Claims 1 and 3-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 67, 68, 70, 71, and 84-88 of copending Application No. 19/077,379 in view of Dennis et al. (US2009/0280056).
It should be noted that the ‘379 application is the latest application in a long unbroken line of continuations and divisional going back to the international application which entered the US national phase and became US patent 9.150.658 discussed above, and thus all biological sequences are identical to those discussed supra concerning the ‘658 and ‘297 patents. The ‘379 application claims human antibodies that bind human TF and have CDRs that are identical to those positively recited by SEQ ID number in instant claim 1, as well as bispecific versions of such antibodies, nucleic acids, vectors, and methods of administering such antibodies to treat disease (see all copending claims, particularly copending claim 1). The copending claims differ from the instant claims in that the copending claims do not recite antibody drug conjugates such as those including MMAE or MMAF.
Dennis et al. disclose methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, examples 3-8, and claim 130). It should be noted that such Ab-drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly paragraphs [0080-0086], [0546-0587] and examples 3 and 6). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (see particularly examples 5 and 6). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (see particularly examples 4 and 8).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the cancer treatment methods of the copending ‘379 application in order to gain the advantages of high killing efficacy as disclosed by Dennis et al. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of Dennis et al. which describe the successful synthesis and use of antibody-auristatin conjugates and the long history of using anti-TF-cytotoxic drug conjugates for treating cancer in the prior art.
Claims 1 and 3-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 67, 68, 70, 71, and 84-88 of copending Application No. 19/077,379 in view of US Patent 7,498,298.
It should be noted that the ‘379 application is the latest application in a long unbroken line of continuations and divisional going back to the international application which entered the US national phase and became US patent 9.150.658 discussed above, and thus all biological sequences are identical to those discussed supra concerning the ‘658 and ‘297 patents. The ‘379 application claims human antibodies that bind human TF and have CDRs that are identical to those positively recited by SEQ ID number in instant claim 1, as well as bispecific versions of such antibodies, nucleic acids, vectors, and methods of administering such antibodies to treat disease (see all copending claims, particularly copending claim 1). The copending claims differ from the instant claims in that the copending claims do not recite antibody drug conjugates such as those including MMAE or MMAF.
The '298 patent discloses methods for conjugating auristatin and its derivatives to antibodies for the treatment of cancer (see entire document, particularly the abstract, sections 4.5-4.8.7, examples 1-33, and claims 1-22). It should be noted that such Ab- drug conjugates include MMAE, MMAF, and the use of valine-citrulline linkers (see particularly tables 2a-2d and examples 24-33). Notably, methods for attaching the drug-linker conjugate to the antibody include partially reducing conditions and the use of sulfhydryl residues (ibid). The disclosed antibody drug conjugates were highly effective against tumor targets both in vivo and in vitro (ibid).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to conjugate MMAE and/or MMAF to the anti- TF antibodies used in the methods of the copending ‘379 application in order to gain the advantages of high killing efficacy as disclosed by the '298 patent. The ordinary artisan would enjoy a reasonable expectation of success in making such conjugates based upon the protocols and working examples of the '298 patent which describe the successful synthesis and use of antibody-auristatin conjugates.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached on Monday-Friday 8:30-5:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Michael Szperka
Primary Examiner
Art Unit 1644
/Michael Szperka/
Primary Examiner, Art Unit 1644
Prosecution Insights