Biotechnology and Biopharmaceuticals: Enzymes as Therapeutic Agents

Comprehensive vocabulary review of therapeutic enzymes, enzyme replacement therapies, engineered biologics, pharmacokinetics, and clinical indications based on Ho & Gibaldi and Crommelin et al.

What are enzymes made from?

Polypeptides

What do enzymes decrease?

activation energy

What can enhance pharmacokinetic properties of enzymes?

Pegylation

What are involved in biochemical pathway?

Enzymes

Do enzymes have a high turnover number?

Yes

What can be recycled after catalyzing a reaction and rapidly transform thousands of molecules?

Enzymes

What must enzymes have in order to work?

Optimum pH & temperature

What is Use of an enzyme to replace a deficient enzyme or a functionally defective endogenous enzyme?

Replacement Therapy

What is Use of an enzyme as a therapeutic molecule?

Therapeutic Agents

What requires timely delivery and removal from the body?

Therapeutic Agents

What maintains the levels of a deficient or aberrant enzyme to sustain its function?

Replacement therapy

What enzyme therapy is used to treat SCID?

Elapegademase-lvlr

What type of enzyme is Elapegademase-lvlr?

PEGylated recombinant adenosine deaminase enzyme

What is the ROA of Elapegademase-lvlr?

IM

What are common reactions to Elapegademase-lvlr?

Cough & vomiting

What is used to monitor Elapegademase-lvlr?

Plasma ADA activity

What should the trough plasma ADA activity be for Elapegademase-lvlr?

>30 mmol/h/L

What causes Gaucher’s disease?

Deficient glucocerebrosidase activity

What enzyme is there a decrease of in Gaucher’s disease>

Glucocerebrosidase

What is there an accumulation of in Gaucher’s disease?

Glucocerebroside

What does Gaucher’s disease weakens?

Bones

What can some patients deal with when getting Gaucher’s disease

CNS damage

What type of receptors does lysosomes have?

mannose-6-phosphate receptors

What is a recombinant formulation of human glucocerebrosidase?

Imiglucerase

Where are Endogenous glucocerebrosidase localized in?

Lysosome

Where are Exogenous glucocerebrosidase accumulated in?

Lysosome

What are treatments for Glucocerebrosidase?

Imiglucerase & Velaglucerase alfa

What is the brand of Velaglucerase alfa?

Vpriv

What is the generic of Cerezym?

Imiglucerase

What is the brand of Imiglucerase?

Cerezyme

What is to improve lysosomal delivery, the enzyme was modified to have exposed mannose? GENERIC

Imiglucerase

What is to improve lysosomal delivery, the enzyme was modified to have exposed mannose? BRAND

Cerezym

Where is Imiglucerase expressed in?

CHO

What was produced in recombinant fibroblasts? GENERIC

Velaglucerase alfa

What was produced in recombinant fibroblasts? BRAND

Vpriv

what is a lysosomal enzyme that mediates the removal of the intracellular sulfate ester from the terminal N-acetylgalactosamine-4-sulfate on GAGs (glycosoaminoglycans), including chondroitin-4-sulfate and dermatan sulfate?

Galsulfase

What is the condition called when there is a Deficiency of the N-acetylgalactosamine-4-sulfatase (galsulfase) causes accumulation of chondroitin-4-sulfate and dermatan sulfate, leading to widespread cellular, tissue, and organ dysfunction?

Mucopolysaccharidosis VI

What is a recombinant galsulfase glycoprotein?

Naglazyme

What is produced in CHO host cells and has a molecular weight of 56 kDa?

Galsulfase

What is a disaccharide made from galactose and glucose?

Lactose

What is lactose made of?

Galactose & glucose

What breaks down lactose?

Lactase

What is used to manage the symptoms associated with lactose intolerance?

Lactase

What is an oncolytic enzyme used for the treatment of acute lymphoblastic leukemia?

L-Asparaginase

What hydrolyzes L-asparagine to ammonia and L-aspartic acid, leading to the depletion of asparagine?

L-Asparaginase

What does L-Asparaginase hydrolyze to ammonia?

L-asparagine

What is L-asparagine hydrolyzed to?

Ammonia & L-aspartic acid

What requires exogenous asparagine?

Leukemia cells

What is often used to treat leukemia?

L-asparaginase

What is metabolized into small peptides by catabolic pathways?

Asparaginase

What is the brand of Asparaginase?

Erwinia & Rylaze

What is the generic of Rylaze?

Asparaginase

What is the generic of Erwinia?

Asparaginase

What is a modified version of L-asparaginase, conjugated with monomethoxypolyethylene glycol?

Pegaspargase

What is the brand of Pegaspargase?

Oncaspar

What is first line treatment for leukemia and patients with hypersensitivity native asparaginase?

Pegaspargase

How is Pegaspargase metabolized?

Systemically degraded

What is a conjugate of L-asparaginase and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate linker?

Calaspargase Pegol

What is the brand name of Calaspargase Pegol?

Asparlas

What is the generic of Asparlas?

Calaspargase Pegol

What drug is used in the management of patients suffering elevated levels of uric acid arising from leukemia/chemotherapy?

Rasburicase

What is the brand of Rasburicase?

Elitek

What is the generic of Elitek?

Rasburicase

Where was rasburicase produced in?

Yeast cells

What is a pegylated recombinant form of urate-oxidase enzyme?

Pegloticase

What is the brand of Pegloticase?

Krystexxa

What is the generic of Krystexxa?

Pegloticase

What is Used for the treatment of cystic fibrosis?

rhDNase I

What is due to a genetic mutation in the gene that makes cystic fibrosis transmembrane regulator?

Cystic fibrosis

What is a recombinant human deoxyribonuclease I, an enzyme that hydrolyzes DNA used to treat cystic fibrosis?

Dornase Alfa

What is the brand of Dornase Alfa?

Pulmozyme

What is the generic of Pulmozyme?

Dornase Alfa

What is slightly engineered to introduce Arg or Lys residues to make the enzyme more positively charged?

Dornase Alfa