DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are currently pending and being examined.
Claim Objections
2. Claims 1-13, 15, 16, and 25 are objected to because of the following informalities: The claims all recite “CECAM6”, where the protein name is misspelled. The name of the protein is CEACAM6. Appropriate correction is required.
3. Claims 15 is objected to because of the following informalities: Claim 15 comprises a hyphen in “SEQ-ID NO:75” that should be deleted.
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.
4. Claims 29, 30, 33, and 34 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 29 depends from claim 25 and claim 29 recites the limitation "the anti-CEACAM6 antibody". There is insufficient antecedent basis for this limitation in the claim because claim 25 recites “anti-CECAM6 antibody” with a different spelling.
Claim 33 depends from claim 25 and claim 33 recites the limitation "the anti-CEACAM6 antibody". There is insufficient antecedent basis for this limitation in the claim because claim 25 recites “anti-CECAM6 antibody” with a different spelling.
Dependent claims 30 and 34 are rejected for encompassing the rejected limitations in claims 29 and 33.
5. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 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 the limitation "…lacking the glycans attached to the conserved N-linked site in the CH2 domains of the Fc region". There is insufficient antecedent basis for this limitation in the claim. Dependent claims are rejected for encompassing the rejected limitation of claim 1.
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.
6. Claims 1-4, 6, 11-13, 15, 16, 25, 29, 30, 33, and 34 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn an anti-CECAM6 antibody that is required to function by:
Bind CECAM6 or CEACAM6 (“anti-CECAM6”);
Compete for CEACAM6 binding with an antibody comprising VH SEQ ID NO:63 and VL SEQ ID NO:67 (claim 4);
Specifically bind to CEACAM6 domain 1 comprising the amino acids 35-142 of SEQ ID NO:75 (claim 15); and
Treat cancer associated with the undesired presence of CECAM6 (claims 25, 29, 30, 33, 34).
Thus, the claims identify the antibody by function only. No antibody structure is recited. The claims broadly encompass any antibody sequence that functions as claimed.
Claim 6 recites a partial sequence structure, wherein the antibody comprises a sequence of CDR SEQ ID NOs:64-66 and 68-70. Thus, the claims encompass antibodies comprising any sequence found in (“of”) the claimed CDR SEQ ID NOs as few as two consecutive amino acids long.
The instant specification discloses that a few other anti-CEACM6 antibodies in the prior art are known (MN-3, Neo201/h16C3, 2A3, and 9A6), but the only antibody identified to modulate CEACAM6 immunosuppressive activity is murine antibody 9A6 that binds to domain 1 of CEACAM6 (p. 6-7). The specification discloses that generation of antibodies binding to domain 1 of CEACAM6 results in a challenging selectivity problem because of the sequence’s high homology to CEACAM3, CEACAM1, and CEACAM5 sequences (p. 8).
The instant specification discloses the sequences of eight anti-CEACAM6 antibodies in Table 0. TPP-21518 comprises instant CDR SEQ ID NOs:64-66 and 68-70, VH and VL SEQ ID NOs:63 and 67, respectively, and HC and LC SEQ ID NOs:71 and 72, respectively (Table 0).
Thus, the instant specification describes the sequence structure of a few exemplary monoclonal anti-CEACAM6 antibodies that function as claimed. The specification fails to disclose the structural sequence required of any other anti-CEACAM6 antibody to possess the claimed functions.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative anti-CEACAM6 antibodies that function as claimed and listed above, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present in the claims is a recitation of the antibody functions as listed above, and partial amino acid sequence. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses a limited number of antibody sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the few disclosed antibodies, the specification fails to provide any structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequences for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
In the instant case, the specification discloses a few exemplary monoclonal anti-CEACAM6 antibodies that function as claimed. The claims broadly encompass any anti-CEACAM6 antibody that functions as claimed. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the variable domains or CDRs that can be altered in the disclosed sequences and still maintain CEACAM6 binding function and perform the other claimed functions. The instant claims attempt to claim every antibody, including monoclonal or humanized, that would achieve a desired result, i.e., bind CEACAM6 or CECAM6, and function as listed above, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses a few representative t monoclonal anti-CEACAM6 antibodies, several of which comprise the same CDR sequences. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of structurally distinct monoclonal anti-CEACAM6 antibodies to the structure of any and all anti-CEACAM6 antibodies as broadly claimed and required to practice the claimed methods. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind CEACAM6 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The CEACAM6 antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed antibodies and those used in the claimed method, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide CEACAM6-binding function and cancer cell treating function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that bind CEACAM6 and function as claimed and listed above that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend claim 1 to recite and require all six CDR SEQ ID NOs as recited in claim 5.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
7. Claim(s) 1-13, 15, 16, 25, 29, 30, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/150899, Willuda et al, published September 2016; in view of Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463).
Willuda teaches an isolated anti-CECAM6 antibody (TPP-3310) comprising variable heavy (VH) region SEQ ID NO:47 and variable light (VL) region SEQ ID NO:51 that are 100% identical to instant SEQ ID NOs:63 and 67 and comprise the instantly claimed CDR sequences (Table 1, p. 33) (see sequence alignments below).
Willuda teaches the antibody comprises light chain (LC) SEQ ID NO:58 or 182 that is 100% identical to instant light chain SEQ ID NO:72 (Table 1, p. 33; Table 28, p. 129) (see sequence alignment below).
Willuda teaches the antibody comprises IgG heavy chain (HC) SEQ ID NO:181 that is 100% identical to instant IgG1 SEQ ID NO:71 except is lacks the three L236A + L237A + N297A mutations in SEQ ID NO:71 (Table 28, p. 129) (see sequence alignment below).
Willuda teaches the antibody is monoclonal, or humanized (p. 28-32).
Willuda nucleic acids encoding the antibody (p. 52-55).
Willuda teaches a method for treating cancer associated with CECAM6 in a subject comprising administering to the subject an effective amount of the antibody (p. 58-64).
Willuda teaches the method of treating cancer further comprises administering an anti-PD-1, anti-PD-L1, or anti-TIM-3 antibody, wherein the anti-PD-1/PD-L1 antibody includes nivolumab, pembrolizumab, atezolizumab, or avelumab (p. 64).
Willuda teaches the therapeutic anti-CEACAM6 antibody functions to relieve CEACAM6-mediated immunosuppression by binding to domain 1 of CEACAM6.Willuda suggests their antibody comprise modifications that alter ADCC or CDC activity. Willuda teaches: “In one embodiment, antibody variants are provided having a carbohydrate structure that lacks fucose attached (directly or indirectly) to an Fc region.” Willuda teaches: “Antibody variants are further provided with bisected oligosaccharides, e.g., in which a biantennary oligosaccharide attached to the Fc region of the antibody is bisected by GlcNAc. Such antibody variants may have reduced fucosylation and/or improved ADCC function.” Willuda identifies Asn297 (N297) on the Fc region where fusocylation normally exists
Willuda suggests reducing ADCC/CDC antibody function: “In certain embodiments, one or more amino acid modifications (e.g. a substitution) may be introduced into the Fc region of an antibody (e.g., a human lgG1 , lgG2, lgG3 or lgG4 Fc region) provided herein, thereby generating an Fc region variant.
In certain embodiments, the invention contemplates an antibody variant that possesses some but not all effector functions, which make it a desirable candidate for applications in which the half-life of the antibody in vivo is important yet certain effector functions (such as complement and ADCC) are unnecessary or deleterious. In vitro and/or in vivo cytotoxicity assays can be conducted to confirm the reduction/depletion of CDC and/or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcyR binding (hence likely lacking ADCC activity), but retains FcRn binding ability. In some embodiments, alterations are made in the Fc region that result in altered (i.e., either improved or diminished) C1q binding and/or Complement Dependent Cytotoxicity (CDC)” (p. 47-50).
Willuda does not teach the heavy chain IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q) as recited in claims 1-3.
Saunders reviews known mutations introduced into the Fc region of therapeutic antibodies that function to reduce the antibody effector function or ADCC/CDC activity, including L234A/L235A (“LALA”) mutations and Asn297ALA or Gly or Gln (N297A, N297G, or N297Q) mutations (Table 3).
Borrok also summarizes known mutations to make “Fc-silenced” therapeutic antibodies with reduced effector function, including IgG1 LALA mutation (L234A/L235A) and lacking IgG N297 glycan (p. 1008, col. 2 to p. 1009, col. 1).
Lo teaches known mutations of reducing the cytotoxic effector function of a therapeutic antibody including the commonly used N297G or N297A mutation and the LALA mutation, all of which function to reduced ACC and CDC activity (p. 3900, col. 2 to p. 3901, col. 1; abstract).
Arduin teaches and successfully exemplifies combining the LALA and N297A mutations in a single therapeutic IgG antibody, wherein the mutations successfully resulted in Fc silencing or reduced effector function (abstract; Introduction; Figure 1, 6, and 7).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to add the LALA and N297A mutations to the antibody of Willuda. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Willuda suggests modifying their therapeutic antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (2) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (3) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
Instant VH SEQ ID NO:63 aligned with Willuda SEQ ID NO:47
RESULT 1
BDG10817
ID BDG10817 standard; protein; 118 AA.
XX
AC BDG10817;
XX
DT 17-NOV-2016 (first entry)
XX
DE Anti-CEACAM6 humanized antibody heavy chain variable region, SEQ ID 47.
XX
KW CD66c; CEACAM6 protein;
KW Carcinoembryonic antigen-related cell adhesion molecule 6; NCA protein;
KW NCA-50; NCA-90; Non-specific crossreacting antigen; antibody production;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antipsoriatic;
KW cancer; cardiant; cerebroprotective; crohns disease; cystic fibrosis;
KW cytostatic; diagnostic test; fibrosis; gastrointestinal-gen.;
KW gingiva disease; heavy chain variable region; humanized antibody;
KW immuno-diagnosis; immunoconjugate; immunosuppressive; infectious disease;
KW inflammatory bowel disease; influenza virus infection; injury;
KW lung infection; myocardial infarction; oral-dental-gen.; pneumonia;
KW prophylactic to disease; psoriasis; respiratory-gen.; sepsis; stroke;
KW surgical procedure; surgical-gen.; therapeutic; vasotropic;
KW viral infection; virucide; vulnerary.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2016150899-A2.
XX
CC PD 29-SEP-2016.
XX
CC PF 21-MAR-2016; 2016WO-EP056104.
XX
PR 23-MAR-2015; 2015EP-00160292.
XX
CC PA (FARB ) BAYER PHARMA AG.
CC PA (DEKR ) DEUT KREBSFORSCHUNGSZENTRUM.
XX
CC PI Willuda J, Trautwein M, Gritzan U, Freiberg C, Dittmer F;
CC PI Schonfeld D, Gluck JM, Bruder J, Schlecker E, Golfier S, Holton S;
CC PI Beckhove P, Ge Y;
XX
DR WPI; 2016-61325L/71.
DR N-PSDB; BDG10825.
XX
CC PT New isolated antibody or fragments of antibody capable of specifically
CC PT binding to human carcinoembryonic antigen-related cell adhesion molecule
CC PT 6 and Macaca fascicularis CEACAM6 used in composition for treating e.g.
CC PT breast cancer.
XX
CC PS Claim 10; SEQ ID NO 47; 183pp; English.
XX
CC The present invention relates to a novel isolated antibody or an antigen-
CC binding fragment thereof specifically binding to a human carcinoembryonic
CC antigen-related cell adhesion molecule 6 (CEACAM6) protein and Macaca
CC fascicularis CEACAM6 protein. The invention further claims: (1) an
CC antibody-drug conjugate comprising the antibody or its antigen binding
CC fragment; (2) an isolated nucleic acid sequence encoding the antibody or
CC its antigen binding fragment; (3) a vector comprising the nucleic acid
CC sequence; (4) an isolated cell expressing the antibody or its antigen-
CC binding fragment; (5) a method for producing the antibody or its antigen-
CC binding fragment; (6) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment; (7) a combination of the
CC pharmaceutical composition and one or more therapeutically active
CC compounds; (8) a method for treating a disease or a condition associated
CC with the undesired presence of CEACAM6 protein; and (9) a process for
CC preparing anti-CEACAM6 antibodies specifically binding to human CEACAM6
CC and Macaca fascicularis CEACAM6. The isolated antibody or its antigen-
CC binding fragment of the present invention can be used in a pharmaceutical
CC composition for diagnosing, preventing and treating cancer, fibrotic
CC disease, lung infection (preferably influenza), Crohns disease,
CC inflammatory bowel disease, psoriasis, lung cystic fibrosis, trauma,
CC bleeding burn, surgery, stroke, myocardial infarction, sepsis, pneumonia,
CC infectious disease and chronic virus infection. The present sequence
CC represents an anti-CEACAM6 humanized antibody (TPP-3310) heavy chain
CC variable region (comprising human framework regions (FRs) and mouse
CC complementarity determining regions (CDRs)), where the antibody can be
CC used for diagnosing, preventing and treating the above-mentioned
CC diseases.
XX
SQ Sequence 118 AA;
Query Match 100.0%; Score 637; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVTLRESGPALVKPTQTLTLTCTFSGFSLSTYGIGVGWIRQPPGKALEWLAHIWWNDNKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVTLRESGPALVKPTQTLTLTCTFSGFSLSTYGIGVGWIRQPPGKALEWLAHIWWNDNKY 60
Qy 61 YSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARISLPYFDYWGQGTTLTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARISLPYFDYWGQGTTLTVSS 118
Instant VL SEQ ID NO:67 aligned with Willuda SEQ ID NO:51
RESULT 1
BDG10821
ID BDG10821 standard; protein; 107 AA.
XX
AC BDG10821;
XX
DT 17-NOV-2016 (first entry)
XX
DE Anti-CEACAM6 humanized antibody light chain variable region, SEQ ID 51.
XX
KW CD66c; CEACAM6 protein;
KW Carcinoembryonic antigen-related cell adhesion molecule 6; NCA protein;
KW NCA-50; NCA-90; Non-specific crossreacting antigen; antibody production;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antipsoriatic;
KW cancer; cardiant; cerebroprotective; crohns disease; cystic fibrosis;
KW cytostatic; diagnostic test; fibrosis; gastrointestinal-gen.;
KW gingiva disease; humanized antibody; immuno-diagnosis; immunoconjugate;
KW immunosuppressive; infectious disease; inflammatory bowel disease;
KW influenza virus infection; injury; light chain variable region;
KW lung infection; myocardial infarction; oral-dental-gen.; pneumonia;
KW prophylactic to disease; psoriasis; respiratory-gen.; sepsis; stroke;
KW surgical procedure; surgical-gen.; therapeutic; vasotropic;
KW viral infection; virucide; vulnerary.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2016150899-A2.
XX
CC PD 29-SEP-2016.
XX
CC PF 21-MAR-2016; 2016WO-EP056104.
XX
PR 23-MAR-2015; 2015EP-00160292.
XX
CC PA (FARB ) BAYER PHARMA AG.
CC PA (DEKR ) DEUT KREBSFORSCHUNGSZENTRUM.
XX
CC PI Willuda J, Trautwein M, Gritzan U, Freiberg C, Dittmer F;
CC PI Schonfeld D, Gluck JM, Bruder J, Schlecker E, Golfier S, Holton S;
CC PI Beckhove P, Ge Y;
XX
DR WPI; 2016-61325L/71.
DR N-PSDB; BDG10826.
XX
CC PT New isolated antibody or fragments of antibody capable of specifically
CC PT binding to human carcinoembryonic antigen-related cell adhesion molecule
CC PT 6 and Macaca fascicularis CEACAM6 used in composition for treating e.g.
CC PT breast cancer.
XX
CC PS Claim 10; SEQ ID NO 51; 183pp; English.
XX
CC The present invention relates to a novel isolated antibody or an antigen-
CC binding fragment thereof specifically binding to a human carcinoembryonic
CC antigen-related cell adhesion molecule 6 (CEACAM6) protein and Macaca
CC fascicularis CEACAM6 protein. The invention further claims: (1) an
CC antibody-drug conjugate comprising the antibody or its antigen binding
CC fragment; (2) an isolated nucleic acid sequence encoding the antibody or
CC its antigen binding fragment; (3) a vector comprising the nucleic acid
CC sequence; (4) an isolated cell expressing the antibody or its antigen-
CC binding fragment; (5) a method for producing the antibody or its antigen-
CC binding fragment; (6) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment; (7) a combination of the
CC pharmaceutical composition and one or more therapeutically active
CC compounds; (8) a method for treating a disease or a condition associated
CC with the undesired presence of CEACAM6 protein; and (9) a process for
CC preparing anti-CEACAM6 antibodies specifically binding to human CEACAM6
CC and Macaca fascicularis CEACAM6. The isolated antibody or its antigen-
CC binding fragment of the present invention can be used in a pharmaceutical
CC composition for diagnosing, preventing and treating cancer, fibrotic
CC disease, lung infection (preferably influenza), Crohns disease,
CC inflammatory bowel disease, psoriasis, lung cystic fibrosis, trauma,
CC bleeding burn, surgery, stroke, myocardial infarction, sepsis, pneumonia,
CC infectious disease and chronic virus infection. The present sequence
CC represents an anti-CEACAM6 humanized antibody (TPP-3310) light chain
CC variable region (comprising human framework regions (FRs) and mouse
CC complementarity determining regions (CDRs)), where the antibody can be
CC used for diagnosing, preventing and treating the above-mentioned
CC diseases.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 555; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQLTQSPSFLSASVGDRVTITCKASQNVGTAVAWYQQKPGKAPKLLIYSASNRYTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQLTQSPSFLSASVGDRVTITCKASQNVGTAVAWYQQKPGKAPKLLIYSASNRYTGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYSSYPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYSSYPLTFGGGTKVEIK 107
Instant LC SEQ ID NO:72 aligned with Willuda SEQ ID NO:182
RESULT 1
BDG10828
ID BDG10828 standard; protein; 214 AA.
XX
AC BDG10828;
XX
DT 17-NOV-2016 (first entry)
XX
DE Anti-CEACAM6 humanized antibody light chain region, SEQ ID 58.
XX
KW CD66c; CEACAM6 protein;
KW Carcinoembryonic antigen-related cell adhesion molecule 6;
KW Immunoglobulin kappa; NCA protein; NCA-50; NCA-90;
KW Non-specific crossreacting antigen; antibody production;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antipsoriatic;
KW cancer; cardiant; cerebroprotective; chimeric antibody; crohns disease;
KW cystic fibrosis; cytostatic; diagnostic test; fibrosis;
KW gastrointestinal-gen.; gingiva disease; humanized antibody;
KW immuno-diagnosis; immunoconjugate; immunosuppressive; infectious disease;
KW inflammatory bowel disease; influenza virus infection; injury;
KW light chain; lung infection; myocardial infarction; oral-dental-gen.;
KW pneumonia; prophylactic to disease; psoriasis; respiratory-gen.; sepsis;
KW stroke; surgical procedure; surgical-gen.; therapeutic; vasotropic;
KW viral infection; virucide; vulnerary.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2016150899-A2.
XX
CC PD 29-SEP-2016.
XX
CC PF 21-MAR-2016; 2016WO-EP056104.
XX
PR 23-MAR-2015; 2015EP-00160292.
XX
CC PA (FARB ) BAYER PHARMA AG.
CC PA (DEKR ) DEUT KREBSFORSCHUNGSZENTRUM.
XX
CC PI Willuda J, Trautwein M, Gritzan U, Freiberg C, Dittmer F;
CC PI Schonfeld D, Gluck JM, Bruder J, Schlecker E, Golfier S, Holton S;
CC PI Beckhove P, Ge Y;
XX
DR WPI; 2016-61325L/71.
DR N-PSDB; BDG10830.
XX
CC PT New isolated antibody or fragments of antibody capable of specifically
CC PT binding to human carcinoembryonic antigen-related cell adhesion molecule
CC PT 6 and Macaca fascicularis CEACAM6 used in composition for treating e.g.
CC PT breast cancer.
XX
CC PS Claim 12; SEQ ID NO 58; 183pp; English.
XX
CC The present invention relates to a novel isolated antibody or an antigen-
CC binding fragment thereof specifically binding to a human carcinoembryonic
CC antigen-related cell adhesion molecule 6 (CEACAM6) protein and Macaca
CC fascicularis CEACAM6 protein. The invention further claims: (1) an
CC antibody-drug conjugate comprising the antibody or its antigen binding
CC fragment; (2) an isolated nucleic acid sequence encoding the antibody or
CC its antigen binding fragment; (3) a vector comprising the nucleic acid
CC sequence; (4) an isolated cell expressing the antibody or its antigen-
CC binding fragment; (5) a method for producing the antibody or its antigen-
CC binding fragment; (6) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment; (7) a combination of the
CC pharmaceutical composition and one or more therapeutically active
CC compounds; (8) a method for treating a disease or a condition associated
CC with the undesired presence of CEACAM6 protein; and (9) a process for
CC preparing anti-CEACAM6 antibodies specifically binding to human CEACAM6
CC and Macaca fascicularis CEACAM6. The isolated antibody or its antigen-
CC binding fragment of the present invention can be used in a pharmaceutical
CC composition for diagnosing, preventing and treating cancer, fibrotic
CC disease, lung infection (preferably influenza), Crohns disease,
CC inflammatory bowel disease, psoriasis, lung cystic fibrosis, trauma,
CC bleeding burn, surgery, stroke, myocardial infarction, sepsis, pneumonia,
CC infectious disease and chronic virus infection. The present sequence
CC represents an anti-CEACAM6 humanized antibody light chain region
CC (comprising an anti-CEACAM6 humanized antibody (TPP-3310) light chain
CC variable region (comprising human framework regions (FRs) and mouse
CC complementarity determining regions (CDRs)) and a human immunoglobulin
CC kappa constant region), where the antibody can be used for diagnosing,
CC preventing and treating the above-mentioned diseases.
XX
SQ Sequence 214 AA;
Query Match 100.0%; Score 1108; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQLTQSPSFLSASVGDRVTITCKASQNVGTAVAWYQQKPGKAPKLLIYSASNRYTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQLTQSPSFLSASVGDRVTITCKASQNVGTAVAWYQQKPGKAPKLLIYSASNRYTGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYSSYPLTFGGGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYSSYPLTFGGGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Instant HC SEQ ID NO:71 aligned with Willuda SEQ ID NO:181
RESULT 4
BDG10951
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BDG10951 standard; protein; 447 AA.
XX
AC BDG10951;
XX
DT 17-NOV-2016 (first entry)
XX
DE Anti-CEACAM6 antibody heavy chain region, SEQ ID 181.
XX
KW CD66c; CEACAM6 protein;
KW Carcinoembryonic antigen-related cell adhesion molecule 6;
KW Immunoglobulin G1; Immunoglobulin gamma 1; NCA protein; NCA-50; NCA-90;
KW Non-specific crossreacting antigen; antibody production;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antipsoriatic;
KW cancer; cardiant; cerebroprotective; chimeric antibody; crohns disease;
KW cystic fibrosis; cytostatic; diagnostic test; fibrosis;
KW gastrointestinal-gen.; gingiva disease; heavy chain; immuno-diagnosis;
KW immunoconjugate; immunosuppressive; infectious disease;
KW inflammatory bowel disease; influenza virus infection; injury;
KW lung infection; myocardial infarction; oral-dental-gen.; pneumonia;
KW prophylactic to disease; psoriasis; respiratory-gen.; sepsis; stroke;
KW surgical procedure; surgical-gen.; therapeutic; vasotropic;
KW viral infection; virucide; vulnerary.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2016150899-A2.
XX
CC PD 29-SEP-2016.
XX
CC PF 21-MAR-2016; 2016WO-EP056104.
XX
PR 23-MAR-2015; 2015EP-00160292.
XX
CC PA (FARB ) BAYER PHARMA AG.
CC PA (DEKR ) DEUT KREBSFORSCHUNGSZENTRUM.
XX
CC PI Willuda J, Trautwein M, Gritzan U, Freiberg C, Dittmer F;
CC PI Schonfeld D, Gluck JM, Bruder J, Schlecker E, Golfier S, Holton S;
CC PI Beckhove P, Ge Y;
XX
DR WPI; 2016-61325L/71.
XX
CC PT New isolated antibody or fragments of antibody capable of specifically
CC PT binding to human carcinoembryonic antigen-related cell adhesion molecule
CC PT 6 and Macaca fascicularis CEACAM6 used in composition for treating e.g.
CC PT breast cancer.
XX
CC PS Disclosure; SEQ ID NO 181; 183pp; English.
XX
CC The present invention relates to a novel isolated antibody or an antigen-
CC binding fragment thereof specifically binding to a human carcinoembryonic
CC antigen-related cell adhesion molecule 6 (CEACAM6) protein and Macaca
CC fascicularis CEACAM6 protein. The invention further claims: (1) an
CC antibody-drug conjugate comprising the antibody or its antigen binding
CC fragment; (2) an isolated nucleic acid sequence encoding the antibody or
CC its antigen binding fragment; (3) a vector comprising the nucleic acid
CC sequence; (4) an isolated cell expressing the antibody or its antigen-
CC binding fragment; (5) a method for producing the antibody or its antigen-
CC binding fragment; (6) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment; (7) a combination of the
CC pharmaceutical composition and one or more therapeutically active
CC compounds; (8) a method for treating a disease or a condition associated
CC with the undesired presence of CEACAM6 protein; and (9) a process for
CC preparing anti-CEACAM6 antibodies specifically binding to human CEACAM6
CC and Macaca fascicularis CEACAM6. The isolated antibody or its antigen-
CC binding fragment of the present invention can be used in a pharmaceutical
CC composition for diagnosing, preventing and treating cancer, fibrotic
CC disease, lung infection (preferably influenza), Crohns disease,
CC inflammatory bowel disease, psoriasis, lung cystic fibrosis, trauma,
CC bleeding burn, surgery, stroke, myocardial infarction, sepsis, pneumonia,
CC infectious disease and chronic virus infection. The present sequence
CC represents an anti-CEACAM6 antibody heavy chain region (comprising a
CC mouse anti-CEACAM6 antibody (TPP-2971) heavy chain variable region and a
CC human immunoglobulin gamma 1 (IgG1) constant region), where the antibody
CC can be used for diagnosing, preventing and treating the above-mentioned
CC diseases.
XX
SQ Sequence 447 AA;
Query Match 99.1%; Score 2381; Length 447;
Best Local Similarity 99.3%;
Matches 444; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 QVTLRESGPALVKPTQTLTLTCTFSGFSLSTYGIGVGWIRQPPGKALEWLAHIWWNDNKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVTLRESGPALVKPTQTLTLTCTFSGFSLSTYGIGVGWIRQPPGKALEWLAHIWWNDNKY 60
Qy 61 YSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARISLPYFDYWGQGTTLTVSSAS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YSTSLKTRLTISKDTSKNQVVLTMTNMDPVDTATYYCARISLPYFDYWGQGTTLTVSSAS 120
Qy 121 TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL 180
Qy 181 YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPS 240
|||||||||||||||||||||||||||||||||||||||||||||||||||||| ||||
Db 181 YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS 240
Qy 241 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYAST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 241 VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST 300
Qy 301 YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT 360
Qy 361 KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ 420
Qy 421 GNVFSCSVMHEALHNHYTQKSLSLSPG 447
|||||||||||||||||||||||||||
Db 421 GNVFSCSVMHEALHNHYTQKSLSLSPG 447
8. Claim(s) 34 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463); as applied to claims 1-13, 15, 16, 25, 29, 30, and 33 above, and further in view of Lee et al (Frontiers in Pharmacology, May 2021, Vol. 12: Article 681320; p. 1-19).
Willuda; Saunders; Borrok; Lo; and Arduin (the combined references) teach an isolated anti-CEACAM6 antibody and methods of treating cancer associated with CEACAM6 in a subject comprising administering the antibody to the subject in combination with an anti-TIM-3 antibody, as set forth above.
The combined references do not teach the TIM-3 antibody is cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390.
Lee reviews known anti-TIM-3 antibodies administered in the treatment of cancer including all of cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab (MBG453), and INCAGN2390 (Tables 2 and 3; p. 11-12).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to utilize any of anti-TIM-3 antibodies cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab (MBG453), or INCAGN2390 in the method of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Willuda suggests administering anti-TIM-3 antibody in their method of treating cancer with the anti-CEACM6 antibody; and (2) Lee teaches several known anti-TIM-3 antibodies in the prior art for the clinical treatment of cancer including cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), and INCAGN2390.
9. Claims 1-13, 15, 16, 25, 29, 30, and 33 are rejected under 35 U.S.C. 103 as being obvious over each of:
US Patent 10,584,167;
US Patent 11,773,164; and
US Patent 11,866,495; each US Patent in view of:
Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463).
Each applied US Patent reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Each US Patent claims priority to the same WO 2016/150899, Willuda et al, published September 2016 document cited above, therefore, they all share the same disclosure as WO 2016/150899, Willuda. The disclosure of Willuda is set forth above.
Each of the US Patents does not teach the heavy chain IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q) as recited in instant claims 1-3.
Saunders reviews known mutations introduced into the Fc region of therapeutic antibodies that function to reduce the antibody effector function or ADCC/CDC activity, including L234A/L235A (“LALA”) mutations and Asn297ALA or Gly or Gln (N297A, N297G, or N297Q) mutations (Table 3).
Borrok also summarizes known mutations to make “Fc-silenced” therapeutic antibodies with reduced effector function, including IgG1 LALA mutation (L234A/L235A) and lacking IgG N297 glycan (p. 1008, col. 2 to p. 1009, col. 1).
Lo teaches known mutations of reducing the cytotoxic effector function of a therapeutic antibody including the commonly used N297G or N297A mutation and the LALA mutation, all of which function to reduced ACC and CDC activity (p. 3900, col. 2 to p. 3901, col. 1; abstract).
Arduin teaches and successfully exemplifies combining the LALA and N297A mutations in a single therapeutic IgG antibody, wherein the mutations successfully resulted in Fc silencing or reduced effector function (abstract; Introduction; Figure 1, 6, and 7).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to add the LALA and N297A mutations to the antibody of each of the US Patents. One would have been motivated to, and have a reasonable expectation of success to, because: (1) each of the US Patents suggests modifying their therapeutic antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (2) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (3) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
10. Claim(s) 34 is rejected under 35 U.S.C. 103 as being unpatentable over each of:
US Patent 10,584,167;
US Patent 11,773,164; and
US Patent 11,866,495;
each in combination with Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463); as applied to claims 1-13, 15, 16, 25, 29, 30, and 33 above, and further in view of Lee et al (Frontiers in Pharmacology, May 2021, Vol. 12: Article 681320; p. 1-19).
Each US Patent; Saunders; Borrok; Lo; and Arduin (the combined references) teach an isolated anti-CEACAM6 antibody and methods of treating cancer associated with CEACAM6 in a subject comprising administering the antibody to the subject in combination with an anti-TIM-3 antibody, as set forth above.
The combined references do not teach the TIM-3 antibody is cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390.
Lee reviews known anti-TIM-3 antibodies administered in the treatment of cancer including all of cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), and INCAGN2390 (Tables 2 and 3; p. 11-12).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to utilize any of anti-TIM-3 antibodies cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390 in the method of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because: (1) each US Patent suggests administering anti-TIM-3 antibody in their method of treating cancer with the anti-CEACM6 antibody; and (2) Lee teaches several known anti-TIM-3 antibodies in the prior art for the clinical treatment of cancer including cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), and INCAGN2390.
11. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are rejected under 35 U.S.C. 103 as being obvious over US Patent 12,221,479 (claiming priority to December 2018), in view of WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
US Patent 12,221,479 (Willuda) teaches an isolated anti-CEACAM6 antibody comprising VH and VL SEQ ID NOs:1 and 5, that are 100% identical to instant SEQ ID NOs:63 and 67, respectively. Willuda teaches the antibody comprises light chain SEQ ID NO:10 that is 100% identical to instant SEQ ID NO:72. Willuda teaches nucleic acids encoding the antibody, humanized and monoclonal antibodies. Willuda teaches methods of treating cancer associated with CEACAM6 expression in a subject comprising administering to the subject the antibody and in combination with anti-TIM-3 antibodies cobolimab, MBG-453, BMS-986258, Sym-023, LY-3321367 or INCAGN-2390 (see claims), or in combination with anti-PD-1/PD-L1 antibodies such as pembrolizumab or atezolizumab.
US Patent 12,221,479 (Willuda) does not teach the heavy chain IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q) as recited in claims 1-3, or that the heavy chain comprises instant SEQ ID NO:71 (claims 9 and 10).
WO 2016/150899 Willuda, Saunders; Borrok; Lo; and Arduin teach as set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to add the LALA and N297A mutations to the antibody heavy chain of the US Patent 12,221,479 (Willuda) and to utilize the known heavy chain SEQ ID NO:181 provided by WO 2016/150899 Willuda (that is 100% identical to instant SEQ ID NO:71 except for the LALA and N297A mutations). One would have been motivated to, and have a reasonable expectation of success to, because: (1) US Patent 12,221,479 (Willuda) teaches utilizing their anti-CEACAM6 antibody for therapeutic treatment of cancer; (2) WO 2016/150899 Willuda suggests modifying the anti-CEACAM6 therapeutic antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function and teaches known heavy chain SEQ ID NO:181; (3) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (4) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
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.
12. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,584,167 in view of WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); Arduin et al (Molecular Immunology, 2015, 63:456-463); and Lee et al (Frontiers in Pharmacology, May 2021, Vol. 12: Article 681320; p. 1-19).
The US Patent claims and renders obvious an isolated anti-CEACAM6 antibody comprising the same CDRs, VH, VL and light chain sequences as the instantly claimed antibody. The US Patent claims the antibody comprises variable heavy (VH) region SEQ ID NO:47 and variable light (VL) region SEQ ID NO:51 that are 100% identical to instant SEQ ID NOs:63 and 67 and comprise the instantly claimed CDR sequences (see sequence alignments for Willuda above). The US Patent claims the antibody comprises light chain (LC) SEQ ID NO:58 that is 100% identical to instant light chain SEQ ID NO:72.
The US Patent claims:
1. An anti-CEACAM6 antibody or an antigen-binding fragment thereof comprising
a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:48, an H-CDR2 comprising SEQ ID NO:49, and an H-CDR3 comprising SEQ ID NO:50 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:52, a L-CDR2 comprising SEQ ID NO:53, and a L-CDR3 comprising SEQ ID NO:54.
2. The antibody or antigen-binding fragment thereof according to claim 1 comprising
a variable heavy chain sequence as presented by SEQ ID NO: 47 and a variable light chain sequence as presented by SEQ ID NO: 51.
3. The antibody according to claim 1, which is an IgG antibody.
4. The antibody according to claim 1 comprising:
a heavy chain region corresponding to SEQ ID NO: 57 and a light chain region corresponding to SEQ ID NO: 58.
5. The antigen-binding fragment according to claim 1, which is an scFv, Fab, Fab′ fragment or a F(ab′)2 fragment.
6. The antibody or antigen-binding fragment according to claim 1, which is a monoclonal antibody or antigen-binding fragment.
7. The antibody or antigen-binding fragment according to claim 1, which is human, humanized or chimeric antibody or antigen-binding fragment.
8. An antibody-drug conjugate, comprising an antibody or antigen binding fragment thereof according to claim 1.
9. An isolated nucleic acid sequence that encodes the antibody or antigen-binding fragment according to claim 1.
10. A vector comprising a nucleic acid sequence according to claim 9.
11. An isolated cell expressing an antibody or antigen-binding fragment according to claim 1.
12. An isolated cell according to claim 11, wherein said cell is a prokaryotic or a eukaryotic cell.
13. A method of producing an antibody or antigen-binding fragment according to claim 1 and purification of the antibody or antigen-binding fragment.
14. A pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 1.
15. A combination of a pharmaceutical composition according to claim 14 and one or more therapeutically active compounds.
16. A method for treating a disorder or condition associated with the undesired presence of CEACAM6, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 14.
The US Patent does not claim the heavy chain comprises instant SEQ ID NO:71 or that the IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q) as recited in instant claims 1-3.
The US Patent does not claim the method of treatment is for cancer and further comprises administering an anti-PD-1, anti-PD-L1, or anti-TIM-3 antibody, wherein the anti-PD-1/PD-L1 antibody includes nivolumab, pembrolizumab, atezolizumab, or avelumab, or wherein the TIM-3 antibody comprises cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390 (instant claims 25, 29, 30, 33, 34).
Willuda, Saunders; Borrok; Lo; and Arduin, and Lee teach as set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to modify the antibody heavy chain of the US Patent to comprise LALA and N297A mutations with the heavy chain the sequence of Willuda SEQ ID NO:181. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims utilizing the anti-CEACAM6 antibody as a therapeutics; (2) Willuda suggests modifying therapeutic anti-CEACAM6 antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (3) Willuda teaches the known heavy chain sequence of an anti-CEACAM6 antibody SEQ ID NO:181; (4) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (5) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to treat cancer as the disorder in the method of the US Patent and to further administer any of the known anti-cancer anti-PD-1/PD-L1 or anti-TIM-3 antibodies. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims administering the anti-CEACAM6 antibody as a therapeutic to treat disorders; (2) Willuda teaches the anti-CEACAM6 antibody treats cancer and suggests further administering anti-PD-1/PD-L1 or anti-TIM-3 antibodies, including nivolumab, pembrolizumab, atezolizumab, or avelumab; and (3) Lee teaches known anti-TIM-3 antibodies clinically administered for the treatment of cancer including cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390.
13. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,773,164 in view of WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); Arduin et al (Molecular Immunology, 2015, 63:456-463); and Lee et al (Frontiers in Pharmacology, May 2021, Vol. 12: Article 681320; p. 1-19).
The US Patent claims and renders obvious an isolated anti-CEACAM6 antibody comprising the same CDRs, VH, VL and light chain sequences as the instantly claimed antibody. The US Patent claims the antibody comprises variable heavy (VH) region SEQ ID NO:119 and variable light (VL) region SEQ ID NO:123 that are 100% identical to instant SEQ ID NOs:63 and 67 and comprise the instantly claimed CDR sequences. The US Patent claims the antibody comprises light chain (LC) SEQ ID NO:130 that is 100% identical to instant light chain SEQ ID NO:72.
The US Patent claims:
1. An isolated anti-CEACAM6 antibody or antigen-binding fragment thereof comprising:
ii. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:106, an H-CDR2 comprising SEQ ID NO:107, and an H-CDR3 comprising SEQ ID NO:108 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:110, a L-CDR2 comprising SEQ ID NO:111, and a L-CDR3 comprising SEQ ID NO:112, or
iii. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:4, an H-CDR2 comprising SEQ ID NO:5, and an H-CDR3 comprising SEQ ID NO:6 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:8, a L-CDR2 comprising SEQ ID NO:9, and a L-CDR3 comprising SEQ ID NO:10, or
iv. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:34, an H-CDR2 comprising SEQ ID NO:35, and an H-CDR3 comprising SEQ ID NO:36 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:38, a L-CDR2 comprising SEQ ID NO:39, and a L-CDR3 comprising SEQ ID NO:40, or
v. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:120, an H-CDR2 comprising SEQ ID NO: 121, and an H-CDR3 comprising SEQ ID NO:122 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:124, a L-CDR2 comprising SEQ ID NO:125, and a L-CDR3 comprising SEQ ID NO:126, or
vi. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:24, an H-CDR2 comprising SEQ ID NO:25, and an H-CDR3 comprising SEQ ID NO:26 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:28, a L-CDR2 comprising SEQ ID NO:29, and a L-CDR3 comprising SEQ ID NO:30, or
vii. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:76, an H-CDR2 comprising SEQ ID NO:77, and an H-CDR3 comprising SEQ ID NO:78 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:80, a L-CDR2 comprising SEQ ID NO:81, and a L-CDR3 comprising SEQ ID NO:82, or
viii. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:134, an H-CDR2 comprising SEQ ID NO:135, and an H-CDR3 comprising SEQ ID NO:136 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO: 138, a L-CDR2 comprising SEQ ID NO:139, and a L-CDR3 comprising SEQ ID NO:140, or
ix. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:148, an H-CDR2 comprising SEQ ID NO:149, and an H-CDR3 comprising SEQ ID NO:150 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:152, a L-CDR2 comprising SEQ ID NO:153, and a L-CDR3 comprising SEQ ID NO:154, or
x. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:14, an H-CDR2 comprising SEQ ID NO:15, and an H-CDR3 comprising SEQ ID NO:16 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:18, a L-CDR2 comprising SEQ ID NO:19, and a L-CDR3 comprising SEQ ID NO:20, or
xi. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:62, an H-CDR2 comprising SEQ ID NO:63, and an H-CDR3 comprising SEQ ID NO:64 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:66, a L-CDR2 comprising SEQ ID NO:67, and a L-CDR3 comprising SEQ ID NO:68, or
xii. a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:92, an H-CDR2 comprising SEQ ID NO:93, and an H-CDR3 comprising SEQ ID NO:94 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:96, a L-CDR2 comprising SEQ D NO:97, and a L-CDR3 comprising SEQ ID NO:98.
2. The antibody or antigen-binding fragment according to claim 1 comprising:
ii. a variable heavy chain sequence as presented by SEQ ID NO: 105 and a variable light chain sequence as presented by SEQ ID NO: 109, or
iii. a variable heavy chain sequence as presented by SEQ ID NO: 3 and a variable light chain sequence as presented by SEQ ID NO: 7, or
iv. a variable heavy chain sequence as presented by SEQ ID NO: 33 and a variable light chain sequence as presented by SEQ ID NO: 37, or
v. a variable heavy chain sequence as presented by SEQ ID NO: 119 and a variable light chain sequence as presented by SEQ ID NO: 123, or
vi. a variable heavy chain sequence as presented by SEQ ID NO: 23 and a variable light chain sequence as presented by SEQ ID NO: 27, or
vii. a variable heavy chain sequence as presented by SEQ ID NO: 75 and a variable light chain sequence as presented by SEQ ID NO: 79, or
viii. a variable heavy chain sequence as presented by SEQ ID NO: 133 and a variable light chain sequence as presented by SEQ ID NO: 137, or
ix. a variable heavy chain sequence as presented by SEQ ID NO: 147 and a variable light chain sequence as presented by SEQ ID NO: 151, or
x. a variable heavy chain sequence as presented by SEQ ID NO: 13 and a variable light chain sequence as presented by SEQ ID NO: 17, or
xi. a variable heavy chain sequence as presented by SEQ ID NO: 61 and a variable light chain sequence as presented by SEQ ID NO: 65, or
xii. a variable heavy chain sequence as presented by SEQ ID NO: 91 and a variable light chain sequence as presented by SEQ ID NO: 95.
3. The antibody according to claim 1 comprising:
ii. a heavy chain region corresponding to SEQ ID NO: 115 and a light chain region corresponding to SEQ ID NO: 116, or
iii. a heavy chain region corresponding to SEQ ID NO: 43 and a light chain region corresponding to SEQ ID NO: 44, or
iv. a heavy chain region corresponding to SEQ ID NO: 129 and a light chain region corresponding to SEQ ID NO: 130, or
v. a heavy chain region corresponding to SEQ ID NO: 85 and a light chain region corresponding to SEQ ID NO: 86, or
vi. a heavy chain region corresponding to SEQ ID NO: 143 and a light chain region corresponding to SEQ ID NO: 144, or
vii. a heavy chain region corresponding to SEQ ID NO: 157 and a light chain region corresponding to SEQ ID NO: 158, or
viii. a heavy chain region corresponding to SEQ ID NO: 71 and a light chain region corresponding to SEQ ID NO: 72, or
ix. a heavy chain region corresponding to SEQ ID NO: 101 and a light chain region corresponding to SEQ ID NO: 102.
4. The antibody according to claim 1, which is an IgG antibody.
5. The antigen-binding fragment according to claim 1, which is a scFv, Fab, Fab′, or F(ab′)2fragment.
6. The antibody or antigen-binding fragment according to claim 1, which is a monoclonal antibody or antigen-binding fragment.
7. The antibody or antigen-binding fragment according to claim 1, which is a human, humanized or chimeric antibody or antigen-binding fragment.
8. An antibody-drug conjugate, comprising an antibody or antigen binding fragment according to claim 1.
9. An isolated nucleic acid that encodes the antibody or antigen-binding fragment according to claim 1.
10. A vector comprising a nucleic acid according to claim 9.
11. An isolated cell expressing an antibody or antigen-binding fragment according to claim 1.
12. The isolated cell according to claim 11, wherein said cell is a prokaryotic or a eukaryotic cell.
13. A method of producing an anti-CEACAM6 antibody or antigen-binding fragment comprising culturing of the cell according to claim 11 and purifying the anti-CEACAM6 antibody or antigen-binding fragment.
14. A pharmaceutical composition comprising the antibody or antigen-binding fragment according to claim 1.
15. A combination of the pharmaceutical composition according to claim 14 and one or more therapeutically active compounds.
16. A method for treating cancer that expresses CEACAM6, comprising administering to a subject in need thereof an effective amount of the antibody or antigen-binding fragment according to claim 1, or of the pharmaceutical composition according to claim 14, or of the combination according to claim 15.
17. A method for treating cancer that expresses CEACAM6, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 14.
18. A method for treating cancer that expresses CEACAM6, comprising administering to a subject in need thereof an effective amount of the combination according to claim 15.
19. A pharmaceutical composition comprising the antibody-drug conjugate according to claim 8.
20. A method for treating cancer that expresses CEACAM6, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 19.
The US Patent does not claim the heavy chain comprises instant SEQ ID NO:71 or that the IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q) as recited in instant claims 1-3.
The US Patent does not claim the method of cancer treatment further comprises administering an anti-PD-1, anti-PD-L1, or anti-TIM-3 antibody, wherein the anti-PD-1/PD-L1 antibody includes nivolumab, pembrolizumab, atezolizumab, or avelumab, or wherein the TIM-3 antibody comprises cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390 (instant claims 25, 29, 30, 33, 34).
Willuda, Saunders; Borrok; Lo; and Arduin, and Lee teach as set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to modify the antibody heavy chain of the US Patent to comprise LALA and N297A mutations with the heavy chain the sequence of Willuda SEQ ID NO:181. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims utilizing the anti-CEACAM6 antibody as a therapeutic; (2) Willuda suggests modifying therapeutic anti-CEACAM6 antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (3) Willuda teaches the known heavy chain sequence of an anti-CEACAM6 antibody SEQ ID NO:181; (4) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (5) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed further administer any of the known anti-cancer anti-PD-1/PD-L1 or anti-TIM-3 antibodies in the method of treating cancer claimed by the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims administering the anti-CEACAM6 antibody as a therapeutic to treat cancer; (2) Willuda teaches the anti-CEACAM6 antibody treats cancer and suggests further administering anti-PD-1/PD-L1 or anti-TIM-3 antibodies, including nivolumab, pembrolizumab, atezolizumab, or avelumab; and (3) Lee teaches known anti-TIM-3 antibodies clinically administered for the treatment of cancer including cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390.
14. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,866,495 in view of WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); Arduin et al (Molecular Immunology, 2015, 63:456-463); and Lee et al (Frontiers in Pharmacology, May 2021, Vol. 12: Article 681320; p. 1-19).
The US Patent claims and renders obvious an isolated anti-CEACAM6 antibody comprising the same CDRs as the instantly claimed antibody. The US Patent claims the antibody comprises CDR SEQ ID NOs:48-50 and 52-54 that are 100% identical to instant SEQ ID NOs:64-66 and 68-70, respectively.
The US Patent claims:
1. An isolated antibody or antigen-binding fragment thereof specifically binding to human CEACAM6, wherein said antibody or antigen-binding fragment:
i. binds to an epitope of human CEACAM6, wherein said epitope comprises the amino acid residues GIn60, Asn61, Arg62, Ile63, Va183, Ile84, Gly85, Thr90, Ser127, Asp128 and Leu129 of SEQ ID NO: 179, and
ii. binds to a human CEACAM6 protein comprising an Ile63Leu mutation and does not bind to a human CEACAM6 protein comprising an 11 e63Phe mutation according to SEQ ID NO: 179, and
wherein the antibody or antigen-binding fragment includes
a) a heavy chain antigen-binding region that comprises an H-CDR1 comprising SEQ ID NO:48, an H-CDR2 comprising SEQ ID NO:49, and an H-CDR3 comprising SEQ ID NO:50 and a light chain antigen-binding region that comprises a L-CDR1 comprising SEQ ID NO:52, a L-CDR2 comprising SEQ ID NO:53, and a L-CDR3 comprising SEQ ID NO:54.
2. The antibody or antigen-binding fragment according to claim 1, which is an IgG antibody.
3. The antibody or antigen-binding fragment according to claim 1, which is a scFv, Fab, Fab′, or F(ab′)2 fragment.
4. The antibody or antigen-binding fragment according to claim 1, which is a monoclonal antibody or antigen-binding fragment.
5. The antibody or antigen-binding fragment according to claim 1, which is a human, humanized or chimeric antibody or antigen-binding fragment.
6. An antibody-drug conjugate, comprising an antibody or antigen binding fragment according to claim 1.
7. An isolated nucleic acid that encodes the antibody or antigen-binding fragment according to claim 1.
8. A vector comprising a nucleic acid according to claim 7.
9. An isolated cell expressing an antibody or antigen-binding fragment according to claim 1.
10. An isolated cell according to claim 9, wherein said cell is a prokaryotic or a eukaryotic cell.
11. A method of producing an antibody or antigen-binding fragment thereof specifically binding to human CEACAM6 comprising culturing of a cell according to claim 9 and purifying the antibody or antigen-binding fragment thereof.
12. A pharmaceutical composition comprising an antibody or antigen-binding fragment according to claim 1.
13. A combination of a pharmaceutical composition according to claim 12 and one or more therapeutically active compounds.
14. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the antibody or antigen-binding fragment according to claim 1.
15. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 12.
16. A method for treating cancer expressing CEACAM6, comprising administering to a subject in need thereof an effective amount of the combination according to claim 13.
17. A pharmaceutical composition comprising an antibody-drug conjugate according to claim 6.
18. A combination of a pharmaceutical composition according to claim 17 and one or more therapeutically active compounds.
19. A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 17.
20. A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the combination according to claim 18.
The US Patent does not claim the light chain comprises instant SEQ ID NO:72 and the heavy chain comprises instant SEQ ID NO:71 or that the IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q).
The US Patent does not claim the method of cancer treatment further comprises administering an anti-PD-1, anti-PD-L1, or anti-TIM-3 antibody, wherein the anti-PD-1/PD-L1 antibody includes nivolumab, pembrolizumab, atezolizumab, or avelumab, or wherein the TIM-3 antibody comprises cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390 (instant claims 25, 29, 30, 33, 34).
Willuda, Saunders; Borrok; Lo; and Arduin, and Lee teach as set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to utilize the light chain of Willuda and modify the antibody heavy chain of the US Patent to comprise LALA and N297A mutations with the heavy chain sequence of Willuda SEQ ID NO:181. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims utilizing the anti-CEACAM6 antibody as a therapeutic; (2) Willuda suggests modifying therapeutic anti-CEACAM6 antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (3) Willuda teaches the known anti-CEACAM6 antibody light chain SEQ ID NO:58 (that is 100% identical to instant SEQ ID NO:72) and the heavy chain sequence of an anti-CEACAM6 antibody SEQ ID NO:181 (missing only the LALA and N297A mutations); (4) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (5) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed further administer any of the known anti-cancer anti-PD-1/PD-L1 or anti-TIM-3 antibodies in the method of treating cancer claimed by the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims administering the anti-CEACAM6 antibody as a therapeutic to treat cancer; (2) Willuda teaches the anti-CEACAM6 antibody treats cancer and suggests further administering anti-PD-1/PD-L1 or anti-TIM-3 antibodies, including nivolumab, pembrolizumab, atezolizumab, or avelumab; and (3) Lee teaches known anti-TIM-3 antibodies clinically administered for the treatment of cancer including cobolimab, Sym023, LY3321367, BMS-986258, Sabatolimab(MBG453), or INCAGN2390.
15. Claims 1-13, 15, 16, 25, 29, 30, 33, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,221,479 in view of WO 2016/150899, Willuda et al, published September 2016; Saunders et al (Frontiers in Immunology, 2019, vol. 10, article 1296, p. 1-20); Borrok et al (Journal of Pharmaceutical Sciences, 2017, 106:1008-1017); Lo et al (Journal of Biological Chemistry, 2017, 292:3900-3908); and Arduin et al (Molecular Immunology, 2015, 63:456-463).
The US Patent claims:
1. A method of treating cancer comprising administering anti-CEACAM6 antibody before, after or with an effective amount of an anti-TIM-3 antibody in the treatment of cancer,
wherein the cancer to be treated expresses CEACAM6,
wherein the anti-CEACAM6 antibody comprises H-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, H-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, H-CDR3 comprising the amino acid sequence of SEQ ID NO: 4, L-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, L-CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and L-CDR3 comprising the amino acid sequence of SEQ ID NO: 8.
2. The method of claim 1, wherein the anti-CEACAM6 antibody comprises a variable heavy chain sequence of SEQ ID NO:1 and a variable light chain sequence of SEQ ID NO:5.
3. The method of claim 1, wherein the anti-CEACAM6 antibody comprises a heavy chain region of SEQ ID NO: 9 and a light chain region of SEQ ID NO: 10.
4. The method of claim 1, wherein the anti-TIM-3 antibody is cobolimab, MBG-453, BMS-986258, Sym-023, LY-3321367 or INCAGN-2390.
5. The method of claim 1, wherein the anti-TIM-3 antibody comprises H-CDR1 comprising the amino acid sequence of SEQ ID NO: 12, H-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, H-CDR3 comprising the amino acid sequence of SEQ ID NO: 14, L-CDR1 comprising the amino acid sequence of SEQ ID NO: 16, L-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and L-CDR3 comprising the amino acid sequence of SEQ ID NO: 18.
6. The method of claim 1, wherein the anti-TIM-3 antibody comprises a variable heavy chain sequence (VH) of SEQ ID NO:11 and a variable light chain sequences (VL) of SEQ ID NO:15.
7. The method of claim 1, wherein the anti-TIM-3 antibody comprises a heavy chain region (HC) of SEQ ID NO: 19 and a light chain region (LC) of SEQ ID NO: 20.
8. The method of claim 1, wherein the cancer is lung cancer, ovarian cancer, mesothelioma, pancreatic cancer, gastric cancer, colorectal cancer, head and neck cancer, bladder cancer, bile duct cancer, breast cancer, cervical cancer, or esophageal cancer.
9. The method of claim 8, wherein the lung cancer is non-small cell lung cancer.
10. The method of claim 1, wherein at least one of the anti-CEACAM6 antibody or an anti-TIM-3 antibody is administered in simultaneous, separate, or sequential combination with one or more pharmaceutical agents.
11. The method of claim 1, wherein the anti-CEACAM6 antibody is in admixture with the anti-TIM-3 antibody.
US Patent SEQ ID NOs:1 and 5 are 100% identical to instant SEQ ID NO:63 and 67, respectively. US Patent SEQ ID NO:10 is 100% identical to instant light chain SEQ ID NO:72. The US Patent method renders obvious the isolated anti-CEACAM6 antibody utilized by the method.
The US Patent does not claim the heavy chain comprises instant SEQ ID NO:71 or that the IgG1 Fc region comprises mutations L234A, L235A, and N297(A, G, or Q).
The US Patent does not claim the method of cancer treatment further comprises administering an anti-PD-1, or anti-PD-L1 antibody, wherein the anti-PD-1/PD-L1 antibody includes nivolumab, pembrolizumab, atezolizumab, or avelumab.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed to modify the antibody heavy chain of the US Patent to comprise LALA and N297A mutations with the heavy chain sequence of Willuda SEQ ID NO:181. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims utilizing the anti-CEACAM6 antibody as a therapeutic; (2) Willuda suggests modifying therapeutic anti-CEACAM6 antibody to have reduced effector function, or reduced ADCC/CDC function, and teaches removal of the N297 fucose results in that function; (3) Willuda teaches the known anti-CEACAM6 antibody light chain SEQ ID NO:58 (that is 100% identical to instant SEQ ID NO:72) and the heavy chain sequence of an anti-CEACAM6 antibody SEQ ID NO:181 (missing only the LALA and N297A mutations); (4) Saunders, Borrok, Lo, and Arduin all teach the LALA and N297 IgG Fc mutations are known, established, and predictably result in reduced effector function, or reduced ADCC/CDC function, in therapeutic antibodies; and (5) Arduin demonstrates that the combination of LALA and N297A mutations in a single antibody predictably result in reduced effector function, or reduced ADCC/CDC function.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was effectively filed further administer any of the known anti-cancer anti-PD-1/PD-L1 antibodies in the method of treating cancer claimed by the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the US Patent claims administering the anti-CEACAM6 antibody as a therapeutic to treat cancer; and (2) Willuda teaches the anti-CEACAM6 antibody treats cancer and suggests further administering anti-PD-1/PD-L1 or anti-TIM-3 antibodies, including nivolumab, pembrolizumab, atezolizumab, or avelumab.
16. Conclusion: No claim is allowed.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642
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