Streptococcus pneumoniae serotype-specific detection assay, reagents and kits
AssigneeMerck Sharp & Dohme Corp.
InventorsZhifeng Chen, Kara S. Cox, Katrina M. Nolan, Gowrisankar Rajam, Jeanette F. E. Roman, Mary Lillian Shank-Retzlaff, Thorsten Verch, Kalpit A. Vora
Life of this patent
Estimating the term…
Abstract
S. pneumoniae is a major cause of community-acquired pneumonia (CAP) in young children, older adults, and those with conditions or medications that compromise their immunity. Since the introduction of pneumococcal vaccines, the disease burden of vaccine serotypes (STs) on invasive pneumococcal disease has reduced; however, the effect on the burden of CAP is less well known, potentially due to a lack of testing for pneumococcal STs.
Claims22
A method for detecting the presence or absence of a pneumococcal serotype (ST) capsular polysaccharide (PnPs) in a sample, the method comprising:
- a) contacting the sample with:
- a first monoclonal antibody (mAb), or a functional variant thereof, that binds the pneumococcal serotype (ST) capsular polysaccharide (PnPs) in the sample to form a first mAb-antigen complex;
- b) contacting the sample with:
- a second monoclonal antibody (mAb), or a functional variant thereof, that binds the pneumococcal serotype (ST) capsular polysaccharide (PnPs) to form a first mAb-antigen-second mAb complex;
- c) contacting the sample with:
- a third antibody that binds the second monoclonal antibody (mAb), or a functional variant thereof, wherein the third antibody is detectably coupled to a reporter molecule;
- d) detecting the presence or absence of the first mAb-antigen-second mAb complex by detecting the reporter molecule;
- wherein the presence of the first mAb-antigen-second mAb complex confirms the presence of a pneumococcal serotype (ST) capsular polysaccharide (PnPs);
- and
- wherein the absence of the first mAb-antigen-second mAb complex is indicative of the absence of a pneumococcal serotype (ST) capsular polysaccharide (PnPs).
A kit for detecting the presence or absence of one or more S. pneumoniae capsular polysaccharide(s) (PnPs) in a sample, wherein said kit comprises:
- a) one or more first monoclonal antibody (mAb), or functional variant thereof, that binds one or more pneumococcal serotype (ST) capsular polysaccharide (PnPs), said antibody, or functional variant thereof, comprises:
- i) six complementarity determining regions (CDRs) selected from the group consisting of SEQ. ID. NOs.:
- 1-6, 21-26, 41-46, 61-66, 81-86, 101-106, 121-126, 141-146, 161-166, 181-186, 201-206, 221-226, 241-246, 261-266, and 281-286;
- ii) a variable heavy chain and a variable light chain having an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 13-14, 33-34, 53-54, 73-74, 93-94, 113-114, 133-134, 153-154, 173-174, 193-194, 213-214, 233-234, 253-254, 273-274, and 293-294;
- or
- iii) a full length light chain and a full length heavy chain having an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 17-18, 37-38, 57-58, 77-78, 97-98, 117-118, 137-138, 157-158, 177-178, 197-198, 217-218, 237-238, 257-258, 277-278, and 297-298;
- b) one or more second monoclonal antibody (mAb), or functional variant thereof, that binds one or more pneumococcal serotype (ST) capsular polysaccharide (PnPs), said antibody, or functional variant thereof, comprises:
- i) six complementarity determining regions (CDRs) selected from the group consisting of SEQ. ID. NOs.:
- 7-12, 27-32, 47-52, 67-72, 87-92, 107-112, 127-132, 147-152, 167-172, 187-192, 207-212, 227-232, 247-252, 267-272, and 287-292;
- ii) a variable heavy chain and variable light chain sequence selected from the group consisting of SEQ ID NOs:
- 15-16, 35-36, 55-56, 75-76, 95-96, 115-116, 135-136, 155-156, 175-176, 195-196, 215-216, 235-236, 255-256, 275-276, and 295-296;
- or
- iii) a full length light and heavy chain sequence selected from the group consisting of SEQ ID NOs:
- 19-20, 39-40, 59-60, 79-80, 99-100, 119-120, 139-140, 159-160, 179-180, 199-200, 219-220, 239-240, 259-260, 279-280, and 299-300;
- c) a third antibody that binds the second monoclonal antibody;
- and
- d) instructions to use said kit.
A monoclonal antibody (mAb), or a functional variant thereof, that specifically binds to a pneumococcal serotype (ST) capsular polysaccharide (PnPs), wherein said mAb comprises:
- a) six complementarity determining regions (CDRs) selected from the group consisting of SEQ. ID. NOs.:
- 1-6, 21-26, 41-46, 61-66, 81-86, 101-106, 121-126, 141-146, 161-166, 181-186, 201-206, 221-226, 241-246, 261-266, 281-286, 7-12, 27-32, 47-52, 67-72, 87-92, 107-112, 127-132, 147-152, 167-172, 187-192, 207-212, 227-232, 247-252, 267-272, and 287-292;
- b) a variable heavy chain and a variable light chain having an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 13-14, 33-34, 53-54, 73-74, 93-94, 113-114, 133-134, 153-154, 173-174, 193-194, 213-214, 233-234, 253-254, 273-274, 293-294, 15-16, 35-36, 55-56, 75-76, 95-96, 115-116, 135-136, 155-156, 175-176, 195-196, 215-216, 235-236, 255-256, 275-276, and 295-296;
- or
- c) a full length light chain and a full length heavy chain having an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 17-18, 37-38, 57-58, 77-78, 97-98, 117-118, 137-138, 157-158, 177-178, 197-198, 217-218, 237-238, 257-258, 277-278, 297-298, 19-20, 39-40, 59-60, 79-80, 99-100, 119-120, 139-140, 159-160, 179-180, 199-200, 219-220, 239-240, 259-260, 279-280, and 299-300.
Dependencies are inferred from the claim text.