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 1-23 are pending and being examined.
Specification/ Drawings
2. The specification and drawings are objected to. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831. Specifically, there are no SEQ ID NOs identified with the sequences disclosed in Figure 1. 37 CFR 1.831 (c) requires that a reference to a particular sequence identifier (i.e., SEQ ID NO:#) be made in the specification and drawings wherever a reference is made to that sequence:
(c) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief Description is clear.
Applicants may obviate the objection by amending the Brief Description of the Drawings or the Drawings to identify the sequence(s).
If Applicants choose to amend the Drawings: any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Specification/Claim Objection – Sequence Rule Objection
3. The specification and claim 5 are objected to. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831). Specifically, there is no SEQ ID NO identified with the sequence disclosed for –(X1)-C-(X2)-CPPCP-, for example on page 8 and recited in claim 5. 37 CFR 1.831 requires that a reference to a particular sequence identifier (i.e., SEQ ID NO:#) be made in the specification wherever a reference is made to that sequence and encompasses amino acid sequences containing 4 or more specifically defined amino acids wherein the amino acids form a single peptide backbone:
(a) Patent applications disclosing nucleotide and/or amino acid sequences by enumeration of their residues, as defined in paragraph (b) of this section, must contain, as a separate part of the disclosure, a computer readable Sequence Listing in XML format (a "Sequence Listing XML"). Disclosed nucleotide or amino acid sequences that do not meet the definition in paragraph (b) of this section must not be included in the "Sequence Listing XML." The "Sequence Listing XML" contains the information of the nucleotide and/or amino acid sequences disclosed in the patent application using the symbols and format in accordance with the requirements of §§ 1.832 through 1.834.
(b) Nucleotide and/or amino acid sequences, as used in this section and §§ 1.832 through 1.835, encompass:
(1) An unbranched sequence or linear region of a branched sequence containing 4 or more specifically defined amino acids, wherein the amino acids form a single peptide backbone; or
(2) An unbranched sequence or linear region of a branched sequence of 10 or more specifically defined nucleotides, wherein adjacent nucleotides are joined by:
(i) A 3' to 5' (or 5' to 3') phosphodiester linkage; or
(ii) Any chemical bond that results in an arrangement of adjacent nucleobases that mimics the arrangement of nucleobases in naturally occurring nucleic acids (i.e., nucleotide analogs).
(c) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief Description is clear.
Specification
4. The disclosure is further objected to because of the following informalities: The instant specification discloses throughout the specification that SEQ ID NO:10 represents the sequence of CDR3 in the variable light (VL) region of antibody M35-1 and M35-2. However, it appears that SEQ ID NO:10 is incorrectly disclosed as “DDNYAWFAY” in the specification and in the sequence listing. It is noted that instant SEQ ID NO:7 is also identified as “DDNYAWFAY” in the specification and in the sequence listing and represents CDR3 in the variable heavy (VH) region of antibody M35-1 and M35-2 (p. 20):
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160
798
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98
326
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(specification p. 21):
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106
356
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The VL of antibody M35-1 and M35-2 does not comprise the sequence “DDNYAWFAY”, therefore SEQ ID NO:10 is not representative of any CDR3 sequence in the VL region (p. 20):
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152
796
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It appears there is an error with the sequence represented as SEQ ID NO:10 and it appears that the CDR3 of the VL region of M35-1 and M35-2 has not been identified by a SEQ ID NO. Appropriate correction is required.
Claim Objections
5. Claims 4 and 9-23 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 4 and 9-23 have not been further treated on the merits.
Claims 1-3 and 5-8 are further examined below.
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.
6. Claims 1 and 3 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 that the antibody comprises two light chains each “comprising: (a3) a light chain variable domain comprising a CDR1 region, a CDR2 region, and a CDR3 region comprising the amino acid sequences of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10, respectively.”
Claim 1 identifies the light chain CDR3 as SEQ ID NO:10.
SEQ ID NO:10 is disclosed as “DDNYAWFAY” in the specification and sequence listing.
The instant specification discloses that SEQ ID NO:10 “DDNYAWFAY” is the CDR3 sequence of the variable heavy (VH) region of antibody M35-1 and M35-2 (see page 21):
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112
390
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Instant SEQ ID NO:10 (DDNYAWFAY) is not found in the disclosed light chain variable regions of antibody M35-1 or M35-2 that comprise CDR1 and CDR2 SEQ ID NOs:8 and 9 (p. 20):
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152
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Instant SEQ ID NO:10 (DDNYAWFAY) is also not found in the disclosed light chain variable regions of antibody M45-1 (p. 20):
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138
796
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Therefore, the correct sequence representing CDR3 in the claimed light chain variable region is unclear.
7. Claims 5-8 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 5 recites:
An isolated antibody, or an antigen-binding portion thereof, comprising: two heavy chains each comprising:
(a) a hinge region comprising an amino acid sequence of: -(X₁)-C-(X₂)-CPPCP-, wherein X1 is a polypeptide segment having 0-7 amino acid residues each independently selected from any amino acid residue that is not a cysteine residue, and X₂ is a polypeptide segment having 2-7 amino acid residues each independently selected from any amino acid residue that is not a cysteine residue;
(b) a human CH1 domain located upstream of and connected to the hinge region, the CH1 domain comprising a cysteine at the position of 142 according to the IMGT numbering scheme;
wherein the antibody specifically binds to human CD73 protein.
First, it is unclear whether both or one of part (a) and (b) are required to be present in the claimed isolated antibody because there is no conjunction word indicating whether the antibody comprises (a) and (b) or comprises (a) or (b).
Second, it is unclear where “upstream of” the hinge region is in the claimed heavy chains, therefore, it is unclear where the human CH1 domain is located.
Third, it is unclear what cysteine the claim is referring to at “position 142 according to the IMGT numbering scheme” because there is no previously recited sequence to apply a numbering scheme to. According to the IMGT scientific chart for numbering IgG CH1 residues, there is no position 142 according to the IMGT numbering scheme anywhere in the CH1 region (see CH1 numbering in IMGT Scientific Chart, printed December 2025; www.imgt.org/IMGTScientificChart/Numbering/Hu_IGHGnber.html).
The metes and bounds of the claimed invention cannot be determined.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
8. Claim(s) 5 and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Application Publication 2016/0145350, Lonberg et al.
Lonberg teaches an anti-CD73 IgG antibody comprising a modified heavy chain hinge region ([39]; [160]; [171]) comprising any of those listed in paragraph [342-343] including SEQ ID NOs:349, 354, 359, 364, and 369 that all comprise 100% of instant SEQ ID NO:29 (ERKSCVECPPCP):
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375
325
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296
324
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283
324
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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.
9. Claim(s) 1, 3, 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/170131, Yu et al, published September 2019 (see English translation); in view of WO 2009/006520, Dall’acqua et al; WO 2010/063746, Goetsch et al; and US Patent Application Publication 2016/0145350, Lonberg et al.
Yu teaches anti-CD73 IgG therapeutic antibodies comprising VH SEQ ID NO:31 that comprises instant SEQ ID NO:1 and CDR SEQ ID NOs:5+6+7 (see sequence alignments below); and comprising VL SEQ ID NO:36 comprising instant SEQ ID NO:2 and CDR SEQ ID NOs:8+9 (see sequence alignment below) (see English translation p.17- 20; Examples 16 and 19). Yu teaches the anti-CD73 antibody can comprise a free cysteine for linkage to a drug to form an antibody drug conjugate (ADC) (see English translation p. 7, 22-24).
Yu does not teach the IgG antibody heavy chain comprises a modified hinge region of instant SEQ ID NO:27 (CKTHTCPPCP), SEQ ID NO:29 (ERKSCVECPPCP), or the hinge region comprises –(X1)-C-(X2)-CPPCP-, wherein X1 is 0-7 amino acid residues that are not cysteine, and X2 is 2-7 amino acid residues that are not cysteine.
Dall’acqua teaches making therapeutic IgG antibodies comprising heavy chains (VH-CH1-hinge-CH2-CH3) with modified hinge regions, wherein the hinge regions can comprise:
SEQ ID NO:202 (Table 4 page 38, “1-CD Invert") that comprises 100% of instant SEQ ID NO:27 (CKTHTCPPCP); or any of
SEQ ID NOs:177, 182, 183, 190, 191, 196, 197, 200-212 that are encompassed by the formula –(X1)-C-(X2)-CPPCP-, wherein X1 is 0-7 amino acid residues that are not cysteine, and X2 is 2-7 amino acid residues that are not cysteine (Table 3 and 4; Figure 38).
Dall’acqua demonstrates successfully engineering IgG therapeutic antibodies with the modified hinges and teaches determining the effects of the modified hinge on antibody therapeutic function, and to screen for improvements in function ([102-118]; [126]; [129-138]; Examples; claims 1-20).
Goetsch also teaches making therapeutic IgG antibodies comprising heavy chain with a modified hinge region, wherein the hinge region can comprise:
SEQ ID NO:37 (claims 1-8, 25-28) that comprises 100% of instant SEQ ID NO:27; or
Numerous hinge sequences in Table 3 that are encompassed by the formula –(X1)-C-(X2)-CPPCP-, wherein X1 is 0-7 amino acid residues that are not cysteine, and X2 is 2-7 amino acid residues that are not cysteine.
Goetsch demonstrates successfully engineering IgG therapeutic antibodies with the modified hinges to determine the effects of the hinge on antibody therapeutic function, and to screen for improvements in function, wherein the antibodies comprise heavy chain constant region CH1-Hinge-CH2-CH3 structure (Examples 2-6).
Lonberg teaches therapeutic anti-CD37 IgG antibodies comprising heavy chains with modified hinge regions, including comprising instant SEQ ID NO:29, as set forth above. Lonberg teaches modifying the hinge regions to enhance therapeutic function such as antibody internalization and CD73 inhibition ([339-340]). Lonberg demonstrates producing anti-CD73 antibodies with the modified heavy chain hinge region and testing the effects on therapeutic function (Examples).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the hinge region of the therapeutic antibody of Yu with any of the hinges disclosed by Dall’acqua, Goetsch, or Lonberg. One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success to because: (1) Yu teaches making therapeutic anti-CD73 antibodies and their known IgG sequences; (2) Dall’acqua, Goetsch, and Lonberg suggest modifying the hinge region of therapeutic IgG antibodies with their hinge sequences to alter and test the effects of the modification on therapeutic function in order to identify improvements in function; and (3) Dall’acqua, Goetsch, and Lonberg demonstrate the known methods and success for modifying IgG antibody heavy chain hinge regions with their mutant hinge sequences and screening for altered function.
Instant VH CDR SEQ ID NOs:5+6+7 aligned with Yu SEQ ID NO:31
RESULT 5
BGT03423
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BGT03423 standard; protein; 118 AA.
XX
AC BGT03423;
XX
DT 31-OCT-2019 (first entry)
XX
DE Humanized anti-CD73 antibody mAb004-VH_HuG.3 VH region, SEQ ID 31.
XX
KW CD73; antimicrobial-gen.; autoimmune disease; cancer; cytostatic;
KW diagnostic test; heavy chain variable region; humanized antibody;
KW immuno-diagnosis; immunoconjugate; immunosuppressive; infectious disease;
KW metabolic disorder; metabolic-gen.; monoclonal antibody;
KW prophylactic to disease; therapeutic.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2019170131-A1.
XX
CC PD 12-SEP-2019.
XX
CC PF 07-MAR-2019; 2019WO-CN077369.
XX
PR 07-MAR-2018; 2018CN-10188351.
PR 24-MAY-2018; 2018CN-10506111.
XX
CC PA (UYFU ) UNIV FUDAN.
XX
CC PI Yu K, Jin R, Liu L;
XX
DR WPI; 2019-78351Y/74.
XX
CC PT New heavy chain variable region of antibody useful for preparing a
CC PT detection reagent, a test plate or a kit and for preventing or treating
CC PT disease associated with CD73, comprises three complementarity determining
CC PT region.
XX
CC PS Claim 13; SEQ ID NO 31; 97pp; Chinese.
XX
CC The present invention relates to a novel antibody heavy chain variable
CC region, useful in preparing an antibody-drug conjugate and in diagnosing,
CC treating or preventing disease associated with CD73. The antibody heavy
CC chain variable region comprises complementarity determining region CDRs
CC of SEQ ID NOs: 1-3, 10-12 and 21-23 (see BGT03393-BGT03395, BGT03402-
CC BGT03404 and BGT03413-BGT03415). The invention also provides: an antibody
CC light chain variable region comprising CDRs of SEQ ID NOs: 4-6, 13-15 and
CC 24-26 (see BGT03396-BGT03398, BGT03405-BGT03407 and BGT03416-BGT03418);
CC an antibody heavy chain and light chain; a recombinant protein comprising
CC antibody heavy chain variable region, light chain variable region, heavy
CC chain and light chain, and an optional tag sequence; a chimeric antigen
CC receptor (CAR) construct comprising ScFv segment of monoclonal antibody
CC specifically binding to CD73; a recombinant immune cell expressing an
CC exogenous CAR construct; the antibody-drug conjugate comprising the
CC antibody, and a coupling moiety bound to the antibody moiety; and a
CC pharmaceutical composition comprising the antibody, immune cell or
CC antibody conjugate, and a pharmaceutically acceptable carrier. The
CC disease associated with CD73 is selected from the group consisting of
CC cancer, autoimmune disease, metabolic-related disease and infectious
CC disease.
XX
SQ Sequence 118 AA;
Query Match 86.9%; Score 163.4; Length 118;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 NYYIY--------------WIYPGNLNIKYNEKFKG------------------------ 22
||||| |||||||||||||||||
Db 31 NYYIYWVRQAPGQRLEWMGWIYPGNLNIKYNEKFKGRVTITADTSASTAYMELSSLRSED 90
Qy 23 --------DDNYAWFAY 31
|||||||||
Db 91 TAVYYCARDDNYAWFAY 107
Instant VH SEQ ID NO:1 aligned with Yu SEQ ID NO:31
RESULT 1
BGT03423
XX
AC BGT03423;
XX
DT 31-OCT-2019 (first entry)
XX
DE Humanized anti-CD73 antibody mAb004-VH_HuG.3 VH region, SEQ ID 31.
XX
KW CD73; antimicrobial-gen.; autoimmune disease; cancer; cytostatic;
KW diagnostic test; heavy chain variable region; humanized antibody;
KW immuno-diagnosis; immunoconjugate; immunosuppressive; infectious disease;
KW metabolic disorder; metabolic-gen.; monoclonal antibody;
KW prophylactic to disease; therapeutic.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2019170131-A1.
XX
CC PD 12-SEP-2019.
XX
CC PF 07-MAR-2019; 2019WO-CN077369.
XX
PR 07-MAR-2018; 2018CN-10188351.
PR 24-MAY-2018; 2018CN-10506111.
XX
CC PA (UYFU ) UNIV FUDAN.
XX
CC PI Yu K, Jin R, Liu L;
XX
DR WPI; 2019-78351Y/74.
XX
CC PT New heavy chain variable region of antibody useful for preparing a
CC PT detection reagent, a test plate or a kit and for preventing or treating
CC PT disease associated with CD73, comprises three complementarity determining
CC PT region.
XX
CC PS Claim 13; SEQ ID NO 31; 97pp; Chinese.
XX
CC The present invention relates to a novel antibody heavy chain variable
CC region, useful in preparing an antibody-drug conjugate and in diagnosing,
CC treating or preventing disease associated with CD73. The antibody heavy
CC chain variable region comprises complementarity determining region CDRs
CC of SEQ ID NOs: 1-3, 10-12 and 21-23 (see BGT03393-BGT03395, BGT03402-
CC BGT03404 and BGT03413-BGT03415). The invention also provides: an antibody
CC light chain variable region comprising CDRs of SEQ ID NOs: 4-6, 13-15 and
CC 24-26 (see BGT03396-BGT03398, BGT03405-BGT03407 and BGT03416-BGT03418);
CC an antibody heavy chain and light chain; a recombinant protein comprising
CC antibody heavy chain variable region, light chain variable region, heavy
CC chain and light chain, and an optional tag sequence; a chimeric antigen
CC receptor (CAR) construct comprising ScFv segment of monoclonal antibody
CC specifically binding to CD73; a recombinant immune cell expressing an
CC exogenous CAR construct; the antibody-drug conjugate comprising the
CC antibody, and a coupling moiety bound to the antibody moiety; and a
CC pharmaceutical composition comprising the antibody, immune cell or
CC antibody conjugate, and a pharmaceutically acceptable carrier. The
CC disease associated with CD73 is selected from the group consisting of
CC cancer, autoimmune disease, metabolic-related disease and infectious
CC disease.
XX
SQ Sequence 118 AA;
Query Match 100.0%; Score 636; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYYIYWVRQAPGQRLEWMGWIYPGNLNIKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYYIYWVRQAPGQRLEWMGWIYPGNLNIKY 60
Qy 61 NEKFKGRVTITADTSASTAYMELSSLRSEDTAVYYCARDDNYAWFAYWGQGTLVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKGRVTITADTSASTAYMELSSLRSEDTAVYYCARDDNYAWFAYWGQGTLVTVSS 118
Instant VL SEQ ID NO:2 aligned with Yu SEQ ID NO:36 (CDR1 and CDR2 underlined):
RESULT 1
BGT03428
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BGT03428 standard; protein; 107 AA.
XX
AC BGT03428;
XX
DT 31-OCT-2019 (first entry)
XX
DE Humanized anti-CD73 antibody mAb004-VK_HuG.1 VL region, SEQ ID 36.
XX
KW CD73; antimicrobial-gen.; autoimmune disease; cancer; cytostatic;
KW diagnostic test; humanized antibody; immuno-diagnosis; immunoconjugate;
KW immunosuppressive; infectious disease; light chain variable region;
KW metabolic disorder; metabolic-gen.; monoclonal antibody;
KW prophylactic to disease; therapeutic.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
XX
FH Key Location/Qualifiers
FT Region 24..34
FT /label= CDR1
FT Region 50..56
FT /label= CDR2
FT Region 89..97
FT /label= CDR3
XX
CC PN WO2019170131-A1.
XX
CC PD 12-SEP-2019.
XX
CC PF 07-MAR-2019; 2019WO-CN077369.
XX
PR 07-MAR-2018; 2018CN-10188351.
PR 24-MAY-2018; 2018CN-10506111.
XX
CC PA (UYFU ) UNIV FUDAN.
XX
CC PI Yu K, Jin R, Liu L;
XX
DR WPI; 2019-78351Y/74.
XX
CC PT New heavy chain variable region of antibody useful for preparing a
CC PT detection reagent, a test plate or a kit and for preventing or treating
CC PT disease associated with CD73, comprises three complementarity determining
CC PT region.
XX
CC PS Claim 13; SEQ ID NO 36; 97pp; Chinese.
XX
CC The present invention relates to a novel antibody heavy chain variable
CC region, useful in preparing an antibody-drug conjugate and in diagnosing,
CC treating or preventing disease associated with CD73. The antibody heavy
CC chain variable region comprises complementarity determining region CDRs
CC of SEQ ID NOs: 1-3, 10-12 and 21-23 (see BGT03393-BGT03395, BGT03402-
CC BGT03404 and BGT03413-BGT03415). The invention also provides: an antibody
CC light chain variable region comprising CDRs of SEQ ID NOs: 4-6, 13-15 and
CC 24-26 (see BGT03396-BGT03398, BGT03405-BGT03407 and BGT03416-BGT03418);
CC an antibody heavy chain and light chain; a recombinant protein comprising
CC antibody heavy chain variable region, light chain variable region, heavy
CC chain and light chain, and an optional tag sequence; a chimeric antigen
CC receptor (CAR) construct comprising ScFv segment of monoclonal antibody
CC specifically binding to CD73; a recombinant immune cell expressing an
CC exogenous CAR construct; the antibody-drug conjugate comprising the
CC antibody, and a coupling moiety bound to the antibody moiety; and a
CC pharmaceutical composition comprising the antibody, immune cell or
CC antibody conjugate, and a pharmaceutically acceptable carrier. The
CC disease associated with CD73 is selected from the group consisting of
CC cancer, autoimmune disease, metabolic-related disease and infectious
CC disease.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 568; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYWTNTRHTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYWTNTRHTGVPS 60
Qy 61 RFSGSGSGTDHTLTISSLQPEDFATYYCQQHYSTPFTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDHTLTISSLQPEDFATYYCQQHYSTPFTFGQGTKLEIK 107
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.
10. Claims 1-3 and 5-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/253,677 (reference application) in view of WO 2019/170131, Yu et al, published September 2019 (see English translation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims an isolated IgG antibody, comprising: two identical heavy chains each comprising (a) a hinge region comprising an amino acid sequence of: -(X₁)-C-(X₂)-CPPCP-, wherein X₁ is a polypeptide segment having 0-7 amino acid residues each independently selected from any amino acid residue that is not a cysteine residue, and X₂ is a polypeptide segment having 2-7 amino acid residues each independently selected from any amino acid residue that is not a cysteine residue; and (b) a CH1 domain located upstream of and connected to the hinge region, the CH1 domain comprising a cysteine at the position of 142 according to the IMGT numbering scheme; the IgG antibody further comprising two identical kappa light chains; wherein the CH1 domain of the IgG antibody has the sequence of that of the CH1 domain of a native human IgG1 antibody with the mutation S142C; wherein the amino acid sequence comprised in the hinge is SEQ ID NO:10 that is 100% identical to instant SEQ ID NO:25, or is SEQ ID NO:28 that is 100% identical to instant SEQ ID NO:26 (see sequence alignments below); wherein the antibody binds to CD73 and is a pharmaceutical; wherein the antibody is conjugated to a drug such as MMAE; and wherein the antibody is reduced at the H-H disulfide bond between each of the cysteine residues in the hinge region to obtain free sulfhydryls for conjugation to a chemical linker containing a terminal thiol reactive group for conjugation to a cytotoxic drug to each of the two heavy chains of the antibody.
The copending application claims the antibody binds to CD73 but does not claim the CDR sequences of a CD73 antibody.
Yu teaches a therapeutic IgG anti-CD73 antibody comprising instant CDR SEQ ID NOs:5+6+7 and 8+9 as set forth above. Yu further teaches anti-CD73 IgG therapeutic antibodies comprising VH SEQ ID NO:38 that comprises instant SEQ ID NO:3 and CDR SEQ ID NOs:11+12+13 (see sequence alignments below); and comprising VL SEQ ID NO:43 comprising instant SEQ ID NO:4 and CDR SEQ ID NOs:14+15+16 (see sequence alignment below).
Yu teaches engineering the anti-CD73 antibody to make a drug conjugate, including by reducing at the H-H disulfide bond between each of the cysteine residues in the hinge region of the heavy chain to obtain free sulfhydryls for conjugation to a chemical linker containing a terminal thiol reactive group for conjugation to a cytotoxic drug to each of the two heavy chains of the antibody. Yu demonstrates conjugating the CD73 antibody to a cytotoxic drug MMAE through the paired cysteines of the IgG antibody (see English translation p. 7-8, 22, 25-26; Examples 23-24).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize the CDR sequences of Yu in the antibody of the copending application. One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success to because: (1) the copending application claims their hinge-modified IgG antibody binds CD73 and is used for drug conjugation and pharmaceuticals; and (2) Yu teaches known therapeutic anti-CD73 IgG antibody CDR sequences, the antibody is used for drug conjugation and pharmaceuticals, and teaches methods for engineering the antibodies utilizing the sequences.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant SEQ ID NO:25 aligned with Application 18/253,677 SEQ ID NO:10:
RESULT 1
US-18-253-677-10
Sequence 10, US/18253677
Publication No. US20240075154A1
GENERAL INFORMATION
APPLICANT: BLISS BIOPHARMACEUTICAL (HANGZHOU) CO., LTD.
TITLE OF INVENTION: ENGINEERED ANTIBODY, ANTIBODY-DRUG CONJUGATE, AND USE THEREOF
FILE REFERENCE: P21408907C
CURRENT APPLICATION NUMBER: US/18/253,677
CURRENT FILING DATE: 2023-05-19
PRIOR APPLICATION NUMBER: PCT/CN2020/130409
PRIOR FILING DATE: 2020-11-20
NUMBER OF SEQ ID NOS: 32
SEQ ID NO 10
LENGTH: 18
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: BB0500-2g&BB0801 Hinge Sequences
Query Match 100.0%; Score 114; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EPPKSCDKTHTVECPPCP 18
||||||||||||||||||
Db 1 EPPKSCDKTHTVECPPCP 18
Instant SEQ ID NO:26 aligned with Application 18/253,677 SEQ ID NO:28:
RESULT 1
US-18-253-677-28
Sequence 28, US/18253677
Publication No. US20240075154A1
GENERAL INFORMATION
APPLICANT: BLISS BIOPHARMACEUTICAL (HANGZHOU) CO., LTD.
TITLE OF INVENTION: ENGINEERED ANTIBODY, ANTIBODY-DRUG CONJUGATE, AND USE THEREOF
FILE REFERENCE: P21408907C
CURRENT APPLICATION NUMBER: US/18/253,677
CURRENT FILING DATE: 2023-05-19
PRIOR APPLICATION NUMBER: PCT/CN2020/130409
PRIOR FILING DATE: 2020-11-20
NUMBER OF SEQ ID NOS: 32
SEQ ID NO 28
LENGTH: 18
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: BR0301&BR0302 Hinge Sequences
Query Match 100.0%; Score 111; Length 18;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EPPKSDCKTKTVECPPCP 18
||||||||||||||||||
Db 1 EPPKSDCKTKTVECPPCP 18
Instant VH SEQ ID NO:3 aligned with Yu SEQ ID NO:38 (CDRs1-3 underlined):
BGT03430
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BGT03430 standard; protein; 119 AA.
XX
AC BGT03430;
XX
DT 31-OCT-2019 (first entry)
XX
DE Humanized anti-CD73 antibody mAb004-VH_HuG0 VH region, SEQ ID 38.
XX
KW CD73; antimicrobial-gen.; autoimmune disease; cancer; cytostatic;
KW diagnostic test; heavy chain variable region; humanized antibody;
KW immuno-diagnosis; immunoconjugate; immunosuppressive; infectious disease;
KW metabolic disorder; metabolic-gen.; monoclonal antibody;
KW prophylactic to disease; therapeutic.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
XX
CC PN WO2019170131-A1.
XX
CC PD 12-SEP-2019.
XX
CC PF 07-MAR-2019; 2019WO-CN077369.
XX
PR 07-MAR-2018; 2018CN-10188351.
PR 24-MAY-2018; 2018CN-10506111.
XX
CC PA (UYFU ) UNIV FUDAN.
XX
CC PI Yu K, Jin R, Liu L;
XX
DR WPI; 2019-78351Y/74.
XX
CC PT New heavy chain variable region of antibody useful for preparing a
CC PT detection reagent, a test plate or a kit and for preventing or treating
CC PT disease associated with CD73, comprises three complementarity determining
CC PT region.
XX
CC PS Claim 13; SEQ ID NO 38; 97pp; Chinese.
XX
CC The present invention relates to a novel antibody heavy chain variable
CC region, useful in preparing an antibody-drug conjugate and in diagnosing,
CC treating or preventing disease associated with CD73. The antibody heavy
CC chain variable region comprises complementarity determining region CDRs
CC of SEQ ID NOs: 1-3, 10-12 and 21-23 (see BGT03393-BGT03395, BGT03402-
CC BGT03404 and BGT03413-BGT03415). The invention also provides: an antibody
CC light chain variable region comprising CDRs of SEQ ID NOs: 4-6, 13-15 and
CC 24-26 (see BGT03396-BGT03398, BGT03405-BGT03407 and BGT03416-BGT03418);
CC an antibody heavy chain and light chain; a recombinant protein comprising
CC antibody heavy chain variable region, light chain variable region, heavy
CC chain and light chain, and an optional tag sequence; a chimeric antigen
CC receptor (CAR) construct comprising ScFv segment of monoclonal antibody
CC specifically binding to CD73; a recombinant immune cell expressing an
CC exogenous CAR construct; the antibody-drug conjugate comprising the
CC antibody, and a coupling moiety bound to the antibody moiety; and a
CC pharmaceutical composition comprising the antibody, immune cell or
CC antibody conjugate, and a pharmaceutically acceptable carrier. The
CC disease associated with CD73 is selected from the group consisting of
CC cancer, autoimmune disease, metabolic-related disease and infectious
CC disease.
XX
SQ Sequence 119 AA;
Query Match 100.0%; Score 631; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTLTSYWMHWVRQAPGQGLEWMGEINPSQGRSNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTLTSYWMHWVRQAPGQGLEWMGEINPSQGRSNY 60
Qy 61 NEKFKSRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARRGVSGNYFDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKSRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARRGVSGNYFDYWGQGTLVTVSS 119
Instant VL SEQ ID NO:4 aligned with Yu SEQ ID NO:43 (CDRs1-3 underlined):
RESULT 1
BGT03435
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BGT03435 standard; protein; 107 AA.
XX
AC BGT03435;
XX
DT 31-OCT-2019 (first entry)
XX
DE Humanized anti-CD73 antibody mAb004-VK_HuG2 VL region, SEQ ID 43.
XX
KW CD73; antimicrobial-gen.; autoimmune disease; cancer; cytostatic;
KW diagnostic test; humanized antibody; immuno-diagnosis; immunoconjugate;
KW immunosuppressive; infectious disease; light chain variable region;
KW metabolic disorder; metabolic-gen.; monoclonal antibody;
KW prophylactic to disease; therapeutic.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
XX
FH Key Location/Qualifiers
FT Region 24..34
FT /label= CDR1
FT Region 50..56
FT /label= CDR2
FT Region 89..97
FT /label= CDR3
XX
CC PN WO2019170131-A1.
XX
CC PD 12-SEP-2019.
XX
CC PF 07-MAR-2019; 2019WO-CN077369.
XX
PR 07-MAR-2018; 2018CN-10188351.
PR 24-MAY-2018; 2018CN-10506111.
XX
CC PA (UYFU ) UNIV FUDAN.
XX
CC PI Yu K, Jin R, Liu L;
XX
DR WPI; 2019-78351Y/74.
XX
CC PT New heavy chain variable region of antibody useful for preparing a
CC PT detection reagent, a test plate or a kit and for preventing or treating
CC PT disease associated with CD73, comprises three complementarity determining
CC PT region.
XX
CC PS Claim 13; SEQ ID NO 43; 97pp; Chinese.
XX
CC The present invention relates to a novel antibody heavy chain variable
CC region, useful in preparing an antibody-drug conjugate and in diagnosing,
CC treating or preventing disease associated with CD73. The antibody heavy
CC chain variable region comprises complementarity determining region CDRs
CC of SEQ ID NOs: 1-3, 10-12 and 21-23 (see BGT03393-BGT03395, BGT03402-
CC BGT03404 and BGT03413-BGT03415). The invention also provides: an antibody
CC light chain variable region comprising CDRs of SEQ ID NOs: 4-6, 13-15 and
CC 24-26 (see BGT03396-BGT03398, BGT03405-BGT03407 and BGT03416-BGT03418);
CC an antibody heavy chain and light chain; a recombinant protein comprising
CC antibody heavy chain variable region, light chain variable region, heavy
CC chain and light chain, and an optional tag sequence; a chimeric antigen
CC receptor (CAR) construct comprising ScFv segment of monoclonal antibody
CC specifically binding to CD73; a recombinant immune cell expressing an
CC exogenous CAR construct; the antibody-drug conjugate comprising the
CC antibody, and a coupling moiety bound to the antibody moiety; and a
CC pharmaceutical composition comprising the antibody, immune cell or
CC antibody conjugate, and a pharmaceutically acceptable carrier. The
CC disease associated with CD73 is selected from the group consisting of
CC cancer, autoimmune disease, metabolic-related disease and infectious
CC disease.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 558; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKASQDINTYLSWFQQKPGKSPKSLIYRSNILVSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCKASQDINTYLSWFQQKPGKSPKSLIYRSNILVSGVPS 60
Qy 61 RFSGSGSGQDYTLTISSLQPEDFATYYCLQYDEFPYTFGGGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGQDYTLTISSLQPEDFATYYCLQYDEFPYTFGGGTKLEIK 107
11. Conclusion: No claim is 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