Antibody mimetics is defined as new scaffold protein which can provide bidning affinity to various antigens. Summary of current antibody scaffold proteins and strategy to differentiate from existing scaffolds.

1. James Jungkue Lee
April, 2012

2.  Binding affinity- mono or avidity
 Immunogenicity
 Pharmacokinetics (T1/2)
 Bio distribution (into tissue)
 Multi-targetability (mono-specific versus bi-specific)
 Engineerability
 Manufactureability
 Yield
 Thermostability
 pH stability
 Structural stability
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3. Antibody Molar
Scaffold Example drug Developer
mimetic mass
Antibody Immunoglobulin 150kDa Herceptin, retuxan etc Genentech etc
Affibody Z domain of Protein 5 kDa ABY-025 (anti-HER2) Affibody AB (SW)
Affilins Gamma-B crystallin 20kDa
Ubiquitin 10kDa SAPVF2 2801 (Preclinical)/ Cancer/imaging Scil Protein Pharmas
(Subnanomolar IC50)
SPVF-2801-30/Cancer solid tumor
Affitins Sac7d (from Sulfolobus acidocaldarius) 7kDa
Anticalins Lipocalins 20kDa
Avimers A domains of various membrane 9-18 kDa C 326 (Stage ?) Avidia  Amgen
receptors Anti-IL-6 avimer (2006, $380mm)
DARPins Ankyrin repeat motif 10-19kDa MP0112 Phase I (with Allergan) Molecular Partners
Anti-VEGFA binder for wet MD, diabetic
macular edema (IC50<10pM, T1/2>6d)
Fynomers SH3 domain of Fyn 7kDa
Kunitz domain Kunitz domains of various protease 6kDa Ecallantide Dyax
peptides inhibitors
Monobodies 10th type III domain of fibronectin 10kDa Angiocept(CT-322), VEGF receptor 2 antagonist Adnexus  BMS
(adnectins) for glioblastoma, NSCLC, CRC (2007, $430mm)
Nanobody Single domain antibody 12-15kDa ALX-0081, against von Willebrand factor, ATN- Ablynx
103 anti TNF alpha (Phase II)
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4. Pipeline
Target Stage IC50 T1/2 Host Remarks
compound
Antibody Various Various Marketed subnano Weeks CHO
Affibody ABY-025 HER2 P1 E.Coli Imaging
Affilins SAPVF2 2801 n/a PC E.Coli
Avimer C 326 IL-6 > P2 50 pM E.Coli CD
E.Coli
DARPin MP0112 VEGFA P1/2a <10 pM >6d Eye
(>200mg/l)
Kunitz
Ecallantide kallikrein M
peptide
Monobody Angiocept VEGFR2
P2 E.Coli
(Adnectin) (CT-322) (KDF for VEGFA)
Nanobody von Willebrand
ALX-0081 P2 E.Coli
(sdAb) factor
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5. 5

6. 6

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8. 8

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10.  Strong binding affinity
 Non-immunogenicity
 Engineerability for PK or drug conjugation
 Molecular properties for manufacturing
 Strong intellectual property right
 Strategic selection of targets
 Enough resource allocation (financing and
HR)
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11.  Affinity?
 Pharmacokinetics?
 Size of molecule?
 Manufacturing yield?
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