Lambrolizumab

STRUCTURAL FORMULA of Lambrolizumab

Heavy chain
QVQLVQSGVE VKKPGASVKV SCKASGYTFT NYYMYWVRQA PGQGLEWMGG 50
INPSNGGTNF NEKFKNRVTL TTDSSTTTAY MELKSLQFDD TAVYYCARRD 100
YRFDMGFDYW GQGTTVTVSS ASTKGPSVFP LAPCSRSTSE STAALGCLVK 150
DYFPEPVTVS WNSGALTSGV HTFPAVLQSS GLYSLSSVVT VPSSSLGTKT 200
YTCNVDHKPS NTKVDKRVES KYGPPCPPCP APEFLGGPSV FLFPPKPKDT 250
LMISRTPEVT CVVVDVSQED PEVQFNWYVD GVEVHNAKTK PREEQFNSTY 300
RVVSVLTVLH QDWLNGKEYK CKVSNKGLPS SIEKTISKAK GQPREPQVYT 350
LPPSQEEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN YKTTPPVLDS 400
DGSFFLYSRL TVDKSRWQEG NVFSCSVMHE ALHNHYTQKS LSLSLGK 447

Light chain
EIVLTQSPAT LSLSPGERAT LSCRASKGVS TSGYSYLHWY QQKPGQAPRL 50′
LIYLASYLES GVPARFSGSG SGTDFTLTIS SLEPEDFAVY YCQHSRDLPL 100′
TFGGGTKVEI KRTVAAPSVF IFPPSDEQLK SGTASVVCLL NNFYPREAKV 150′
QWKVDNALQS GNSQESVTEQ DSKDSTYSLS STLTLSKADY EKHKVYACEV 200′
THQGLSSPVT KSFNRGEC 218′
Disulfide bridges
22-96 22”-96” 23′-92′ 23”’-92”’ 134-218′ 134”-218”’ 138′-198′ 138”’-198”’
147-203 147”-203” 226-226” 229-229” 261-321 261”-321” 367-425 367”-425”
Glycosylation sites (N)
Asn-297 Asn-297”

MOLECULAR FORMULA C6504H10004N1716O2036S46 (peptide)
MOLECULAR WEIGHT 146.3 kDa (peptide)
TRADEMARK None as yet
SPONSOR Merck Sharp & Dohme Corp.
CAS REGISTRY NUMBER 1374853-91-4

THERAPEUTIC CLAIM Antineoplastic, immunomodulatory, immunotherapy
CHEMICAL NAMES
1. Immunoglobulin G4, anti-(human protein PDCD1 (programmed cell death 1))
(human-Mus musculus monoclonal heavy chain), disulfide with human-Mus
musculus monoclonal light chain, dimer

2. Immunoglobulin G4, anti-(human programmed cell death 1); humanized
mouse monoclonal [228-L-proline(H10
-S>P)]γ4 heavy chain (134-218′)-disulfide
with humanized mouse monoclonal κ light chain dimer (226-226”:229-229”)-
bisdisulfide

04/24/2013

Merck announced that the U.S. Food and Drug Administration (FDA) has designated lambrolizumab (MK-3475) as a Breakthrough Therapy for the treatment of patients with advanced melanoma. Lambrolizumab is Merck’s investigational antibody therapy targeting the programmed death receptor (PD-1) that is currently being evaluated for the treatment of patients with advanced melanoma, and other tumor types.

Merck & Co. Inc., also known as MSD outisdeUS and Canada, a provider of health solutions through prescription medicines, vaccines, biologic therapies, animal health, and consumer care products, Wednesday announced that the US Food and Drug Administration or FDA has designated its investigational antibody therapy, Lambrolizumab or MK-3475 as a Breakthrough Therapy for the treatment of patients with advanced melanoma, and other tumor types.

The Food and Drug Administration Safety and Innovation Act includes a provision that allows sponsors to request that an investigational drug be designated as a Breakthrough Therapy.

Lambrolizumab is targeting Programmed Death receptor or PD-1 that is currently being evaluated for the treatment of patients with advanced melanoma, and other tumor types. Advanced melanoma accounts for more than 80 percent of skin cancer-related deaths and one to two percent of all cancer deaths in the United States.

Gary Gilliland, senior vice president and oncology franchise head of Merck Research Laboratories stated, “”The FDA’s decision to place lambrolizumab in a category that may enable expedited development and review is an important milestone for Merck as we advance ongoing programs in multiple cancer indications.”

FDA spokeswoman Sandy Walsh noted that “the concept behind ‘breakthrough’ is that, with increased communication, FDA will work with new drug developers to help design efficient ways to study the safety and effectiveness of their drug.” The agency indicated that it has received 45 requests for breakthrough status designation, with 11 requests approved and 18 requests rejected. Other drugs granted breakthrough status include: Johnson & Johnson and Pharmacyclics’ ibrutinib for mantle cell lymphoma and other cancers; Novartis’ LDK378 for certain patients with non-small-cell lung cancer; and Pfizer’s palbociclib for breast cancer.

The Merck drug is an antibody designed to help the body’s immune system go after cancer cells. Lambrolizumab, also known as MK-3475, specifically targets the “programmed death” 1 receptor, or PD-1, which cancer cells can exploit to escape destruction by the immune system. Bristol-Myers Squibb Co. also is developing an anti-PD-1 drug, nivolumab, that is in Phase 3 testing.

image credit    http://anewmerckreviewed.wordpress.com/

http://anewmerckreviewed.wordpress.com/2013/04/24/merck-oncology-candidate-granted-breakthrough-designation-at-fda-but-bmss-nivolumab-is-out-ahead-on-timelines/