Photo of proteins

Consistency: PeliCRM197® shows higher purity than CRM197 expressed in alternate platforms

Scalability:  Continuity from milligrams for research to kilograms for commercial production

Compliance: PeliCRM197® is the only recombinant CRM197 with demonstrated cGMP availability since 2011

PeliCRM197® is CRM197, a non-toxic mutant of diphtheria toxin having a single amino acid substitution of glycine to glutamic acid at position 52. CRM197 is a well-defined protein and functions as a carrier for polysaccharides and haptens, making them immunogenic.

It is utilized as a carrier protein in a number of approved conjugate vaccines for diseases such as Streptococcus pneumoniae, Haemophilus influenzae b and Neisseria meningitidis. PeliCRM197® is a recombinant, soluble form produced in Pseudomonas fluorescens using the Pelican Expression Technology™ platform. 

Formerly sold by Pfenex, PeliCRM197® is the ideal carrier protein or immunological adjuvant for conjugate vaccines.  CRM197 has been used commercially in prophylactic vaccines since 1990.  Current research and development areas include immunotherapies and anti-addiction vaccines.  PeliCRM197® is similar in both structure and function to the protein produced in C. diphtheriae, as shown in physicochemical and in vivo studies.” 


A Drug Master File (DMF) is a confidential, detailed dossier submitted to the US FDA which contains the proprietary information on the manufacture and safety of a drug component. Ligand will submit a letter authorizing FDA to review the CRM197 DMF in conjunction with their review of a customer-filed IND using PeliCRM197® as an active substance starting material in the manufacture of their product(s). Ligand will also provide a copy of this authorization letter to each customer for inclusion in their IND. Since the DMF mechanism is not available in the EU or elsewhere in the world, Ligand will supply the necessary information regarding PeliCRM197® required to complete our customers’ regulatory filings. This information will be supplied in a format consistent with CTD Module 2 and Module 3, to be easily incorporated into non-US regulatory filings.


  • Mycogen acquired by The Dow Chemical Company- initiation of P. fluorescens platform development
  • Launch of Pfenex Expression Technology Platform®
  • First Clinical Supply Agreement initiated for cGMP CRM197 
  • Initial filing of CRM197 DMF to US FDA 
  • Launch of  Pneumosil® (WHO), made using PeliCRM197®
  • Pfenex acquired by Ligand Pharmaceuticals 
  • BLA filing for V114, which uses CRM197 made in Pelican Expression Technology®
  • Launch of Pneumosil® (India) 
  • Pfenex Expression Technology® rebranded to Pelican Expression Technology®
  • Launch of PeliCRM197® branding


Please see below for a sample of references that discuss CRM197:

The amino-acid sequence of two non-toxic mutants of diphtheria toxin: CRM45 and CRM197.
Nucleic Acids Research | By G Giannini, R Rappuoli, and G Ratti | May 25, 1984

Abstract: The amino-acid sequences of two diphtheria toxin-related, non-toxic proteins, CRM45 and CRM197 , were deduced from the complete sequence of their genes: tox 45 and tox 197. CRM45 lacks the last 149 C-terminal amino-acid residues, but is otherwise identical to diphtheria toxin: a single C—-T transition introduces an “ochre” (TAA) termination signal in tox 45, after the codon for threonine-386. A single G—-A transition was also found in tox 197, leading to the substitution of glycine-52, present in the wild-type toxin, with glutamic acid in CRM197 . This aminoacid change is responsible for the loss of the NAD:EF2 ADP-ribosyltransferase activity in CRM197 , due most probably to an alteration of the NAD+ binding site.

Identification of diphtheria toxin receptor and a nonproteinous diphtheria toxin-binding molecule in Vero cell membrane
Journal of Cell Biology | By: Mekada, E., and Uchida, T. J. | August 1, 1988

Abstract: Two substances possessing the ability to bind to diphtheria toxin (DT) were found to be present in a membrane fraction from DT-sensitive Vero cells. One of these substances was found on the basis of its ability to bind DT and inhibit its cytotoxic effect. This inhibitory substance competitively inhibited the binding of DT to Vero cells. However this inhibitor could not bind to CRM197, the product of a missense mutation in the DT gene, and did not inhibit the binding of CRM197 to Vero cells. Moreover, similar levels of the inhibitory activity were observed in membrane fractions from DT-insensitive mouse cells, suggesting the inhibitor is not the DT receptor which is specifically present in DT-sensitive cells. The second DT-binding substance was found in the same Vero cell membrane preparation by assaying the binding of 125I-labeled CRM197. Such DT-binding activity could not be observed in membrane preparation from mouse L cells. From competition studies using labeled DT and CRM proteins, we conclude that this binding activity is due to the surface receptor for DT. Treatment of these substances with several enzymes revealed that the inhibitor was sensitive to certain RNases but resistant to proteases, whereas the DT receptor was resistant to RNase but sensitive to proteases. The receptor was solubilized and partially purified by chromatography on CM- Sepharose column. Immunoprecipitation and Western blotting analysis of the partially purified receptor revealed that a 14.5-kD protein is the DT receptor, or at least a component of it.