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 20-38 are pending and being examined.
Specification
2. The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Examiner suggests a title relevant to the claimed invention of bispecific CD3 κλ-bodies.
3. Table 15 of the specification discloses:
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260
678
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The Table is confusing because the Table’s title and left column of the table indicate the SEQ ID NOs inside the table should represent GPC3 or CD3 antibody light and heavy chains of the GPC3xCD3 bispecific antibody. However, the top row of the table states that the sequences are of CD20 light and heavy chains. Clarification is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
4. Claims 20-38 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 20 recites the limitations "the second light chain CDR of the second binding domain" and “the heavy second heavy chain CDR of the second binding domain”. There is insufficient antecedent basis for these limitations in the claim.
Further, claim 20 recites selecting CDR from a list of CDR1, CDR2, and CDR3 SEQ ID NOs but does not recite a conjunction word at the end of the list of light chain and heavy chain CDR selections to indicate whether the CDR sets are listed alternatively or in combination. Dependent claims are rejected for depending on and encompassing the rejected limitations of claim 20.
To obviate the rejection, Examiner suggests amending claim 20 to recite:
…wherein the second light chain comprises CDR1, CDR2, and CDR3 sequences selected from the group consisting of: (i) SEQ ID NOs: 7, 8, 9, respectively; (ii) SEQ ID NOs: 14, 15, 9, respectively; and (iii) SEQ ID NOs: 7, 8, 21, respectively; and
the second heavy chain comprises CDR1, CDR2, and CDR3 sequences selected from the group consisting of: (i) SEQ ID NOs: 26, 27, 28, respectively; (ii) SEQ ID NOs: 31, 27, 28, respectively; (iii) SEQ ID NOs: 31, 27, 34, respectively; (iv) SEQ ID NOs: 31, 27, 37, respectively; (v) SEQ ID NOs: 31, 27, 40, respectively; (vi) SEQ ID NOs: 31, 27, 43, respectively; and (vii) SEQ ID NOs: 46, 47, 28, respectively.
5. Claims 22 and 28 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 22 recites the bispecific antibody or antigen binding fragment thereof according to claim 20, wherein a second light chain variable region of the second antigen-binding portion has a Gln40Glu mutation (VλCD3: Gln40Glu); and a second heavy chain variable region of the second antigen-binding portion has a Gln39Lys mutation (VHCD3: Gln39Lys).
There is no previous mention of a second light chain variable region of the second antigen-binding portion in claim 20, and there is no VλCD3 sequence or VHCD3 sequence recited anywhere to provide a frame of reference to identify where and which Gln is at position 40 and where and which Gln is at position 39. Therefore, it is unclear what amino acids the claim is referencing.
Claim 28 recites the first antigen-binding portion and/or second antigen-binding portion of the bispecific antibody further has a Ser228Pro, Leu235Glu, and/or Pro329Ala mutation.
There is no sequence recited that would allow one to identify where and which amino acids are Ser228, Leu235, and Pro329. Therefore, it is unclear what amino acids the claim is referencing.
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 20-38 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 to a bispecific antibody comprising (a) a first antigen binding portion wherein the antigen is not BCMA; and a second antigen binding portion wherein the second antigen is CD3; wherein the second antigen-binding portion comprises a defined set of light chain CDR1-3 SEQ ID NOs and/or a defined set of heavy chain CDR1-3 SEQ ID NOs recited in claim 20.
Thus claim 20 encompass a vast genus of bispecific antibodies comprising a first antigen-binding portion of unknown structure that functions NOT to bind BCMA; and a second CD3-binding portion requiring only partial sequence structure (only the light chain CDRs-13 or only the heavy chain CDRs1-3) critical to the CD3-binding function.
Claims 21, 23, and 24 further define and require at least the six CDR SEQ ID NOs from the light and heavy chain critical to the CD3-binding function of the second antigen binding portion, however, none of the recited claims recite the sequence structure of the first antigen binding portion or fragment thereof that is critical to the antigen-binding function.
Dependent claims 26, 27, 37, and 38 further define the antigen being bound (i.e., CD20, GPC3, etc.), however, the claims do not recite the sequence structure of the first antigen binding portion critical to binding the identified tumor antigen.
Dependent claims 36-38 further require the bispecific antibody function to treat cancer
Thus, the claims encompass a vast genus of bispecific antibodies comprising: (1) any unidentified first antigen binding portion structure identified by function only and no antibody sequence structure (all claims), and (2) a second CD3-bidning portion identifying and requiring only three CDR sequences from either the light chain or heavy chain (claims 20, 22, 25-29, 31-38).
The instant specification discloses the six heavy and light chain CDR sequences for six highly homologous anti-CD3 antibodies having overlapping CDR sequences (Table 1). The instant specification dislcoses the light chain and heavy chain sequences of highly homologous anti-CD20 antibodies having overlapping CDR sequences (Table 3). As stated above, Table 15 is unclear with regard to what sequences represent GPC3 antibody. The instant specification discloses making CD3xCD20 bispecific antibodies that function to bind CD20 expressing tumor cells and CD3 expressing T cells, activating T cells (Examples 3-5), wherein the bispecific antibodies all comprise six CDR sequences critical to CD3 binding function, and six CDR sequences critical to CD20 binding function.
Thus, the instant specification describes species of highly homologous anti-CD3 antibodies comprising six CDR SEQ ID NOs critical to the CD3-binding function; and species of highly homologous anti-CD20 antibodies comprising six CDR SEQ ID NOs critical to the CD20-binding function required as claimed. The specification fails to disclose the recognizable sequence/structure required of a “first antigen-binding portion” to possess the function of binding an antigen that is not BCMA, and treat cancer, as broadly claimed. The specification fails to disclose any variant anti-CD3 antibodies having only one set of defined CDR1-3 SEQ ID NOs from either the light or the heavy chain.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibodies that function to bind an antigen that is not BCMA or variants of anti-CD3 antibodies comprising only one set of defined heavy or light chain CDR sequences, 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.
Although Applicants may argue that it is possible to screen for antibodies that bind an antigen that is not BCMA or bind CD3 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 claimed antigens provide no information about the structure of an antibody that binds to them.
The instant specification fails to describe structural features common to the members of the first antigen-binding portion genus and members of the partially defined CD3-bidning portion genus, or which features constitute a substantial portion of the genus, because the instant specification discloses the sequences of only a handful of representative anti-CD20 antibodies and anti-CD3 antibodies 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 disclosed anti-CD3 and anti-CD20 antibodies having six fully defined CDR SEQ ID NOs critical to their antigen-binding function and cancer-treating function, 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 first antigen-binding portions and genus of anti-CD3 binding portions having only three defined CDR sequences, and that function as claimed. One could not readily envision members of the broadly claimed genus based on the claimed functions or partial CDR sequence. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of bispecific antibody required to perform the claimed method.
Given the lack of representative examples to support the full scope of the first and second antigen-binding portions required to make and use the claimed bispecific antibody, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide first antigen-binding function that is not to BCMA, the second CD3-binding function, and the cancer-treating function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of first and second antigen-binding portions 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: If the CD3 antibody sequences are the novel aspect of the bispecific antibody invention, amend claim 20 to recite and require, at minimum, the six CDR SEQ ID NOs of second antigen-binding portion that binds to CD3 (see the suggested amendment for claim 20 above in section 4). If the CD3 antibody sequences are not the novel aspect of the bispecific antibody invention, Examiner suggests additionally amending claim 20 to recite and require at least six identifiable CDR SEQ ID NOs from the heavy and light chain of the first antigen-binding portion critical to the antigen binding function.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
6. Claim(s) 20-37 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US Patent Application Publication 20230330257, Wang, claiming priority to August 26, 2020 (Application 18/023,332).
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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
Wang teaches a CD3xCD20 bispecific antibody wherein the CD3 antibody comprises a λ light chain and the CD20 antibody comprises a κ light chain, and wherein the CD3 antibody comprises the same heavy and light chain sequences as instantly claimed in claims 20-24 (see sequence alignments of light and heavy chain sequences below). Wang teaches a nucleic acid encoding the bispecific antibody, vector comprising the nucleic acid, host cell comprising the nucleic acid or vector, a kit comprising the bispecific antibody, composition comprising bispecific antibody, conjugate covalently attached to a therapeutic agent, the bispecific antibody comprising a CD3 lambda chain with Gln40Glu mutation and CD3 heavy chain Gln39Lys mutation; and the bispecific antibody comprising a Ser228Pro, Leu235Glu, and/or Pro329Ala mutation. Wang teaches methods of treating a CD20-associated cancer in a subject comprising administering the bispecific antibody to the subject, wherein the cancer is selected from non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), multiple myeloma (MM), and Hodgkin lymphoma (HL). See claims 1-13; paragraphs [80-220], [254]; [269]; Table 5; and Examples 3-6.
Instant light chain SEQ ID NO:58 aligned with Wang SEQ ID NO:106:
RESULT 1
US-18-023-332-106
Sequence 106, US/18023332
Publication No. US20230330257A1
GENERAL INFORMATION
APPLICANT: BEIJING TIANNUOJIANCHENG PHARMA TECH CO., LTD.
TITLE OF INVENTION: DEVELOPMENT OF DRUG THERAPEUTIC AGENT CONTAINING ADAPTOR AND USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 16610-20014.00
CURRENT APPLICATION NUMBER: US/18/023,332
CURRENT FILING DATE: 2023-02-24
PRIOR APPLICATION NUMBER: PCT/CN2021/114847
PRIOR FILING DATE: 2021-08-26
PRIOR APPLICATION NUMBER: CN 202010873215.X
PRIOR FILING DATE: 2020-08-26
NUMBER OF SEQ ID NOS: 123
SEQ ID NO 106
LENGTH: 215
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1132; Length 215;
Best Local Similarity 100.0%;
Matches 215; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPWT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPWT 60
Qy 61 PARFSGSLLGGKAALTITGAQAEDEAEYYCVLWYSNLWVFGGGTKLTVLGQPKAAPSVTL120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTITGAQAEDEAEYYCVLWYSNLWVFGGGTKLTVLGQPKAAPSVTL120
Qy 121 FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY180
Qy 181 LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 215
|||||||||||||||||||||||||||||||||||
Db 181 LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 215
Instant heavy chain SEQ ID NO:60 aligned with Wang SEQ ID NO:108:
RESULT 1
US-18-023-332-108
Sequence 108, US/18023332
Publication No. US20230330257A1
GENERAL INFORMATION
APPLICANT: BEIJING TIANNUOJIANCHENG PHARMA TECH CO., LTD.
TITLE OF INVENTION: DEVELOPMENT OF DRUG THERAPEUTIC AGENT CONTAINING ADAPTOR AND USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 16610-20014.00
CURRENT APPLICATION NUMBER: US/18/023,332
CURRENT FILING DATE: 2023-02-24
PRIOR APPLICATION NUMBER: PCT/CN2021/114847
PRIOR FILING DATE: 2021-08-26
PRIOR APPLICATION NUMBER: CN 202010873215.X
PRIOR FILING DATE: 2020-08-26
NUMBER OF SEQ ID NOS: 123
SEQ ID NO 108
LENGTH: 452
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 2426; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVGRIRSKYNNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVGRIRSKYNNYAT 60
Qy 61 YYADSVKDRFTISRDDSKNSLYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTL120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYADSVKDRFTISRDDSKNSLYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTL120
Qy 121 VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA180
Qy 181 VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE240
Qy 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ300
Qy 301 FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLASSIEKTISKAKGQPREPQVYTLPPCQ360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLASSIEKTISKAKGQPREPQVYTLPPCQ360
Qy 361 EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS420
Qy 421 RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 452
||||||||||||||||||||||||||||||||
Db 421 RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 452
Instant light chain SEQ ID NO:66 aligned with Wang SEQ ID NO:114:
RESULT 1
US-18-023-332-114
Sequence 114, US/18023332
Publication No. US20230330257A1
GENERAL INFORMATION
APPLICANT: BEIJING TIANNUOJIANCHENG PHARMA TECH CO., LTD.
TITLE OF INVENTION: DEVELOPMENT OF DRUG THERAPEUTIC AGENT CONTAINING ADAPTOR AND USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 16610-20014.00
CURRENT APPLICATION NUMBER: US/18/023,332
CURRENT FILING DATE: 2023-02-24
PRIOR APPLICATION NUMBER: PCT/CN2021/114847
PRIOR FILING DATE: 2021-08-26
PRIOR APPLICATION NUMBER: CN 202010873215.X
PRIOR FILING DATE: 2020-08-26
NUMBER OF SEQ ID NOS: 123
SEQ ID NO 114
LENGTH: 215
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1132; Length 215;
Best Local Similarity 100.0%;
Matches 215; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPGQAPRGLIGGTNKRAPWT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPGQAPRGLIGGTNKRAPWT 60
Qy 61 PARFSGSLLGGKAALTITGAQAEDEAEYYCVLWYSNLWVFGGGTKLTVLGQPKAAPSVTL120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTITGAQAEDEAEYYCVLWYSNLWVFGGGTKLTVLGQPKAAPSVTL120
Qy 121 FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY180
Qy 181 LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 215
|||||||||||||||||||||||||||||||||||
Db 181 LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 215
Instant heavy chain SEQ ID NO:68 aligned with Wang SEQ ID NO:116:
RESULT 1
US-18-023-332-116
Sequence 116, US/18023332
Publication No. US20230330257A1
GENERAL INFORMATION
APPLICANT: BEIJING TIANNUOJIANCHENG PHARMA TECH CO., LTD.
TITLE OF INVENTION: DEVELOPMENT OF DRUG THERAPEUTIC AGENT CONTAINING ADAPTOR AND USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 16610-20014.00
CURRENT APPLICATION NUMBER: US/18/023,332
CURRENT FILING DATE: 2023-02-24
PRIOR APPLICATION NUMBER: PCT/CN2021/114847
PRIOR FILING DATE: 2021-08-26
PRIOR APPLICATION NUMBER: CN 202010873215.X
PRIOR FILING DATE: 2020-08-26
NUMBER OF SEQ ID NOS: 123
SEQ ID NO 116
LENGTH: 452
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 2426; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRKAPGKGLEWVGRIRSKYNNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRKAPGKGLEWVGRIRSKYNNYAT 60
Qy 61 YYADSVKDRFTISRDDSKNSLYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTL120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYADSVKDRFTISRDDSKNSLYLQMNSLKTEDTAVYYCVRHGNFGNSYVSWFAYWGQGTL120
Qy 121 VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA180
Qy 181 VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFE240
Qy 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ300
Qy 301 FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLASSIEKTISKAKGQPREPQVYTLPPCQ360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLASSIEKTISKAKGQPREPQVYTLPPCQ360
Qy 361 EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS420
Qy 421 RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 452
||||||||||||||||||||||||||||||||
Db 421 RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 45
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) 20, 25-29, 31-37 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 10,544,220, Engelberts et al, issued January 28, 2020, filed July 5, 2017; in view of WO 2012/023053, Fischer et al; and Fischer 2015 (Nature Communications, 2015, 6:6113, internet pages 1-12) and Supplementary Information.
Engelberts teaches a bispecific CD3xCD20 antibody, wherein the antibody comprises: (i) anti-CD3 heavy chain variable domain selected from SEQ ID NOs:25 and 6-9 that comprises 100% of instant heavy chain CDR SEQ ID NOs:26+27+28; and (ii) anti-CD3 light chain variable domain selected from SEQ ID NOs: 26, 31, and 10-12 that comprises 100% of instant light chain CDR SEQ ID NOs:7+8+9 (Table 1) (see sequence alignments below).
Engelberts teaches kits comprising the bispecific antibody (claim 10; col. 83, lines 34-50); compositions comprising the bispecific antibody (col. 68-70; col. 83, lines 30-33; claim 11); drug conjugates of the bispecific antibody comprising a therapeutic covalently attached to the antibody (col. 68); a nucleic acid and vector encoding the bispecific antibody, and cell comprising the nucleic acid or vector (col. 46-49).
Engelberts teaches the bispecific antibody is assembled by complementary CH3 Fc domains comprising knobs-into-holes structure (col. 36, lines 44-49; col. 43, lines 53-65; col. 2, lines 54-57).
Engelberts teaches methods of treating subjects with CD20-expressing cancer comprising administering a pharmaceutical composition comprising the bispecific antibody, wherein the cancer is NHL, ALL, CLL, MCL, DLBCL, HL, or MM (col. 71-74; col. 83, lines 1-30).
Engelberts suggests the bispecific antibody can be formatted as a κλ-body, citing WO 2012023053, Fischer (col. 36, line 66 to col. 37, line 10), but does not demonstrate making a CD3xCD20 κλ-body, where the CD3 antibody comprises a λ light chain and CD20 antibody comprises a κ light chain.
WO 2012023053, Fischer teaches methods for successfully making and isolating bispecific κλ-bodies comprising a λ light chain and a κ light chain (see Examples; Figures 3-8) and teaches the advantages of making bispecific antibodies as κλ-bodies including ease of production and isolation, scalable production, and formation of stable antibodies ([83-86]; [111]). Fischer teaches:
[0084] The methods of generating the bispecific and/or multi-specific antibodies of the invention are advantageous because they employ generic purification processes as shown in Figure 8 A. Figure 16 demonstrates purification and product integrity testing of bispecific antibodies purified from a semi-stable cell line. The bispecific antibodies were purified using the following three-step affinity chromatography procedure: (i) Protein A purification to capture IgG molecules, including both monospecific and bispecific; (ii) KappaSelect purification to capture IgG containing Kappa light chain(s); (iii) LambdaSelect purification to capture IgG containing Lambda light chain. The flow-through and elution from each affinity purification steps were analyzed by SDS-PAGE. The results demonstrated the removal of each monospecific form (i.e. , monospecific IgG molecules having Kappa light chains and monospecific IgG molecules having Lambda light chains) during the purification process (Figure 16A). The purified κλ-containing antibodies (i.e., antibodies having both Kappa and Lambda light chains) contained equivalent amount of Kappa and Lambda light chains (Figure 16B). The purified κλ-containing antibodies presented an intermediate migration pattern on an isoelectric focusing gel as compared to the two monospecific antibodies (Figure 16C).
[0085] The chemically defined processes for manufacturing the bispecific and/or multi- specific antibodies of the invention can be used with either pools of CHO cells or with established cell lines. The results obtained with the chemically defined process using either pools or established cell lines demonstrate comparable productivities and growth characteristics to those expressing the corresponding Kappa or Lambda monospecific antibodies. Thus, the κλ-body conserves both the structure and manufacturing characteristics of a classical human IgG.
[0086] Previous approaches to produce bispecific antibody formats aimed at forcing the production of a homogenous bispecific molecule using the different antibody engineering approaches described above were done at the expense of productivity, scalability and stability of the product. The present invention is a different approach that allows the production of a simple mixture of antibodies that have the standard characteristics of productivity and scalability of monoclonal antibodies and provides efficient and generic means to purify the bispecific antibody from the mixture or to purify the antibody mixture.
Fischer suggests bispecific antibodies can be created with a first arm binding CD3 and a second arm binding CD20 ([63]).
Fischer 2015 demonstrates successfully producing a CD3xEpCAM bispecific κλ-body, wherein the CD3 antibody comprises the λ light chain and the EpCam antibody comprises the κ light chain (Figures 1 and 3; p. 6, col. 1; Supplementary Table 3). Fischer teaches that κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Fisher teaches the κλ-body has two different light chain constant domains for robust downstream processing that is compatible with industrial-scale manufacturing (abstract; p. 2, col. 1). Fischer teaches and demonstrates this technology can be used to make κλ-bodies comprising known antibody VH sequences (p. 8, col. 2).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make the CD3xCD20 bispecific antibody of Engelberts as a κλ-body where the CD3 antibody comprises a λ light chain and CD20 antibody comprises a κ light chain. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Engelberts suggests their CD3xCD20 antibody can be produced using known methods including κλ-body production methods, citing WO 2012023053, Fischer; (2) both Fischer references teach the advantages of producing bispecific antibodies as κλ-bodies including scalable industrial production, antibody stability, ease of production and isolation, and their retained pharmacokinetic properties indistinguishable from therapeutic antibodies; (3) WO 2012023053, Fischer teaches and demonstrates known successful methods for producing bispecific κλ-bodies and suggests bispecific antibodies with a first arm binding CD3 and a second arm binding CD20; and (4) Fischer 2015 demonstrates successfully producing a CD3 bispecific κλ-body where the CD3 antibody comprises a λ light chain and the second tumor antigen-binding antibody comprises a κ light chain.
Instant SEQ ID NOs:26+27+28 aligned with US Patent 10,544,220, Engelberts SEQ ID NOs:25, 9, 6, 7, and 8:
US-15-541-594-25
Filing date in PALM: 2017-07-05
Sequence 25, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 25
LENGTH: 125
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 88.5%; Score 189.3; Length 125;
Best Local Similarity 44.7%;
Matches 38; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 NTYAMN---------------IRSKYNNYATYYADSVKD--------------------- 24
|||||| ||||||||||||||||||
Db 30 NTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSQSILYLQMNNLK 89
Qy 25 -----------HGNFGNSYVSWFAY 38
||||||||||||||
Db 90 TEDTAMYYCVRHGNFGNSYVSWFAY 114
US-15-541-594-9
Filing date in PALM: 2017-07-05
Sequence 9, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 9
LENGTH: 125
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 88.5%; Score 189.3; Length 125;
Best Local Similarity 44.7%;
Matches 38; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 NTYAMN---------------IRSKYNNYATYYADSVKD--------------------- 24
|||||| ||||||||||||||||||
Db 30 NTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKSILYLQMNSLK 89
Qy 25 -----------HGNFGNSYVSWFAY 38
||||||||||||||
Db 90 TEDTAMYYCVRHGNFGNSYVSWFAY 114
US-15-541-594-6
Filing date in PALM: 2017-07-05
Sequence 6, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 6
LENGTH: 125
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 88.5%; Score 189.3; Length 125;
Best Local Similarity 44.7%;
Matches 38; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 NTYAMN---------------IRSKYNNYATYYADSVKD--------------------- 24
|||||| ||||||||||||||||||
Db 30 NTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKSSLYLQMNNLK 89
Qy 25 -----------HGNFGNSYVSWFAY 38
||||||||||||||
Db 90 TEDTAMYYCVRHGNFGNSYVSWFAY 114
US-15-541-594-7
Filing date in PALM: 2017-07-05
Sequence 7, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 7
LENGTH: 125
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 88.5%; Score 189.3; Length 125;
Best Local Similarity 44.7%;
Matches 38; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 NTYAMN---------------IRSKYNNYATYYADSVKD--------------------- 24
|||||| ||||||||||||||||||
Db 30 NTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKSILYLQMNNLK 89
Qy 25 -----------HGNFGNSYVSWFAY 38
||||||||||||||
Db 90 TEDTAMYYCVRHGNFGNSYVSWFAY 114
US-15-541-594-8
Filing date in PALM: 2017-07-05
Sequence 8, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 8
LENGTH: 125
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 88.5%; Score 189.3; Length 125;
Best Local Similarity 44.7%;
Matches 38; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 NTYAMN---------------IRSKYNNYATYYADSVKD--------------------- 24
|||||| ||||||||||||||||||
Db 30 NTYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKSILYLQMNSLK 89
Qy 25 -----------HGNFGNSYVSWFAY 38
||||||||||||||
Db 90 TEDTAMYYCVRHGNFGNSYVSWFAY 114
Instant light chain SEQ ID NOs:7+8+9 aligned with US Patent 10,544,220, Engelberts SEQ ID NOs:11, 26, 31, 12, 10:
US-15-541-594-11
Filing date in PALM: 2017-07-05
Sequence 11, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 11
LENGTH: 109
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 85.4%; Score 143.4; Length 109;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RSSTGAVTTSNYAN--------------GGTNKRAP------------------------ 22
|||||||||||||| ||||||||
Db 23 RSSTGAVTTSNYANWVQQTPGQAFRGLIGGTNKRAPGVPARFSGSILGNKAALTITGAQA 82
Qy 23 --------ALWYSNLWV 31
|||||||||
Db 83 DDESIYFCALWYSNLWV 99
US-15-541-594-26
Filing date in PALM: 2017-07-05
Sequence 26, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 26
LENGTH: 109
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 85.4%; Score 143.4; Length 109;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RSSTGAVTTSNYAN--------------GGTNKRAP------------------------ 22
|||||||||||||| ||||||||
Db 23 RSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGVPARFSGSLIGDKAALTITGAQT 82
Qy 23 --------ALWYSNLWV 31
|||||||||
Db 83 EDEAIYFCALWYSNLWV 99
US-15-541-594-31
Filing date in PALM: 2017-07-05
Sequence 31, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 31
LENGTH: 109
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 85.4%; Score 143.4; Length 109;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RSSTGAVTTSNYAN--------------GGTNKRAP------------------------ 22
|||||||||||||| ||||||||
Db 23 RSSTGAVTTSNYANWVQQKPGQAFRGLIGGTNKRAPGVPARFSGSLIGDKAALTITGAQA 82
Qy 23 --------ALWYSNLWV 31
|||||||||
Db 83 DDESIYFCALWYSNLWV 99
US-15-541-594-12
Filing date in PALM: 2017-07-05
Sequence 12, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 12
LENGTH: 109
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 85.4%; Score 143.4; Length 109;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RSSTGAVTTSNYAN--------------GGTNKRAP------------------------ 22
|||||||||||||| ||||||||
Db 23 RSSTGAVTTSNYANWVQQTPGQAFRGLIGGTNKRAPGVPARFSGSILGNKAALTITGAQA 82
Qy 23 --------ALWYSNLWV 31
|||||||||
Db 83 DDESDYYCALWYSNLWV 99
US-15-541-594-10
Filing date in PALM: 2017-07-05
Sequence 10, US/15541594
Patent No. 10544220
GENERAL INFORMATION
APPLICANT: Genmab A/S
TITLE OF INVENTION: BISPECIFIC ANTIBODIES AGAINST CD3 AND CD20
FILE REFERENCE: GMI-147USE
CURRENT APPLICATION NUMBER: US/15/541,594
CURRENT FILING DATE: 2017-07-05
PRIOR APPLICATION NUMBER: PCT/EP2016/050296
PRIOR FILING DATE: 2016-01-08
PRIOR APPLICATION NUMBER: PCT/EP2015/050276
PRIOR FILING DATE: 2015-01-08
PRIOR APPLICATION NUMBER: PA 2015 00412
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00413
PRIOR FILING DATE: 2015-07-15
PRIOR APPLICATION NUMBER: PA 2015 00415
PRIOR FILING DATE: 2015-07-16
PRIOR APPLICATION NUMBER: PA 2015 00416
PRIOR FILING DATE: 2015-07-16
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 10
LENGTH: 109
TYPE: PRT
ORGANISM: Mus Musculus
ALIGNMENT:
Query Match 85.4%; Score 143.4; Length 109;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RSSTGAVTTSNYAN--------------GGTNKRAP------------------------ 22
|||||||||||||| ||||||||
Db 23 RSSTGAVTTSNYANWVQQTPGQAFRGLIGGTNKRAPGVPARFSGSLIGDKAALTITGAQA 82
Qy 23 --------ALWYSNLWV 31
|||||||||
Db 83 DDESIYFCALWYSNLWV 99
8. Claim(s) 38 is rejected under 35 U.S.C. 103 as being unpatentable over US Patent 10,544,220, Engelberts et al, issued January 28, 2020, filed July 5, 2017; WO 2012/023053, Fischer et al; and Fischer 2015 (Nature Communications, 2015, 6:6113, internet pages 1-12 and Supplementary Information; as applied to claims 20, 25-29, 31-37 above, and further in view of Ishiguro et al (Cancer Res (2016) 76 (14_Supplement): DDT01-05).
Engelberts, and both Fischer references (the combined references) teach making and using a CD3xCD20 or CD3xTAA bispecific κλ-body as set forth above. Fischer 2015 further teaches and demonstrates making an anti-GPC3 antibody that comprises a kappa or lambda light chain (Table 1; p. 3, col. 1; Supplementary Table 2). Engelberts further teaches the CD3xCD20 bispecific antibody binds CD3 on T cells and CD20 on tumors cells, directing T cell-mediated killing of cells that express CD20 (abstract; col. 3).
The combined references do not teach the CD3 bispecific antibody binds GPC3 and treats GPC3-expressing cancer.
Ishiguro teaches making a bispecific CD3xGPC3 antibody for the treatment of cancer, wherein the bispecific antibody functions to direct T cell-mediated killing of cells that express GPC3, and wherein the cancer expresses GPC3 and is hepatocellular, gastric, or lung cancer (see entire abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make a CD3xGPC3 bispecific κλ-body for the treatment of GPC3-expressing cancer. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Fischer 2015 suggests and demonstrates successfully applying the κλ-body production technology to both CD3 and GPC3 antibodies; (2) WO 2012/023053, Fischer suggests making a bispecific κλ-body with a first arm targeting an expressed tumor antigen and a second arm targeting CD3 on T cells; (3) both Fischer 2015 and Ishiguro teach the known function of CD3x TAA antibodies is to direct T cells to tumor cell killing; and (4) Ishiguro teaches the known production and success of CD3xGPC3 bispecific antibodies for the treatment of GPC3-expressing cancer.
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.
9. Claims 20-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-18 of copending Application No. 18/023,332 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application is claiming a CD3xCD20 bispecific antibody, wherein the CD3 heavy chain comprises SEQ ID NO:92 that comprises 100% of instant CDR SEQ ID Nos:26+27+28; and the CD3 light chain comprises SEQ ID NO:90 that comprises 100% of instant CDR SEQ ID NOs:7+8+21 and λ light chain region; wherein the CD20 light chain sequence is SEQ ID NO:98 that comprises a κ chain sequence; nucleic acids and vectors encoding the bispecific antibody, cell containing the nucleic acid, a composition comprising the bispecific antibody, the bispecific antibody conjugated covalently to a therapeutic agent; a kit comprising the bispecific antibody; and methods of treating a subject with a CD20-related cancer by administering the bispecific antibody, wherein the cancer is selected from non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), multiple myeloma (MM), and Hodgkin lymphoma (HL). Thus, the copending claimed species of bispecific antibody anticipates and renders obvious the instantly claimed bispecific antibody and limitations utilizing or comprising the antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 20-36 and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/265,114 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application is claiming a CD3xGPC3 bispecific antibody, wherein the CD3 heavy chain comprises SEQ ID NO:168 that is 100% identical to instant SEQ ID NO:68; and the CD3 light chain comprises SEQ ID NO:166 that is 100% identical to instant SEQ ID NO:66 and comprises a λ light chain region; wherein the GPC3 light chain sequence is SEQ ID NO:162 that comprises a κ chain sequence; the bispecific antibody comprising a CD3 lambda chain with Gln40Glu mutation and CD3 heavy chain Gln39Lys mutation; the antibody comprising knobs-into-holes format; nucleic acids and vectors encoding the bispecific antibody, cell containing the nucleic acid, a composition comprising the bispecific antibody, the bispecific antibody conjugated covalently to a therapeutic agent; a kit comprising the bispecific antibody; and methods of treating a subject with a GPC3-related cancer by administering the bispecific antibody, wherein the cancer is liver cancer, pancreatic, hepatocellular, lung, colon, breast, or prostate cancer, leukemia or lymphoma. Thus, the copending claimed species of bispecific antibody anticipates and renders obvious the instantly claimed bispecific antibody and limitations utilizing or comprising the antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
11. Conclusion: No claims are allowed.
12. 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