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Formulation Development for Antibody-Drug Conjugates

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Antibody-Drug Conjugates

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 17))

Abstract

Antibody–drug conjugates (ADCs) are complex molecules designed to provide targeted therapy to cancer patients. An ADC is formed commonly by conjugating an antibody with small cytotoxic drugs generally either through lysine ε-amino groups to form a lysine-linked ADC or through sulfhydryl groups of reducing interchain cystine. THIOMAB®–drug conjugates (TDCs) are a new subclass of ADCs in which the engineered free cysteine residues at specific sites of the antibody are conjugated with cytotoxins. The majority of ADCs currently in the market and under development contains a common moiety: a thio-succinimide linker that is susceptible to hydrolysis of succinimide and cleavage of the thioether bond. ADC contains a heterogeneous mixture of different drug-loaded antibody species, whereas TDC exhibits a more homogeneous distribution of linker drugs. Linker stability, drug load distribution, and drug-to-antibody ratio (DAR) are believed to play critical roles in the efficacy and safety of ADC products. This chapter describes analytical methods and formulation strategies to understand and characterize these critical quality attributes in order to develop a stable formulation for ADC product. The effect of DAR on ADC aggregation is presented. In addition, formulation parameters such as pH and buffers, antioxidants, and surfactants are described. Finally, the advantages and drawbacks of a lyophilized formulation are discussed.

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References

  • Abdul-Fattah AM, Truong-Le V, Yee L, Nguyen L, Kalonia DS, Cicerone MT, Pikal MJ (2007a) Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability (I): stability of a monoclonal antibody. J Pharm Sci 96:1983–2008

    Article  CAS  PubMed  Google Scholar 

  • Abdul-Fattah AM, Truong-Le V, Yee L, Pan E, Ao Y, Kalonia DS, Pikal MJ (2007b) Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on stability II: stability of a vaccine. Pharm Res 24:715–727

    Article  CAS  PubMed  Google Scholar 

  • Abdul-Fattah AM, Dellerman KM, Bogner RH, Pikal MJ (2007c) The effect of annealing on the stability of amorphous solids: chemical stability of freeze-dried moxalactam. J Pharm Sci 96:1237–1250

    Article  CAS  PubMed  Google Scholar 

  • Abdul-Fattah AM, Lechuga-Ballesteros D, Kalonia DS, Pikal MJ (2008) The impact of drying method and formulation on the physical properties and stability of methionyl human growth hormone in the amorphous solid state. J Pharm Sci 97:163–184

    Article  CAS  PubMed  Google Scholar 

  • Acchione M, Kwon H, Jochheim CM, Atkins WM (2012) Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates. MAbs 4:362–372

    Article  PubMed Central  PubMed  Google Scholar 

  • Adem YT, Schwarz KA, Duenas E, Patapoff TW, Galush WJ, Esue O (2014) Auristatin antibody drug conjugate physical instability and the role of drug payload. Bioconjug Chem 25(4):656–664

    Article  CAS  PubMed  Google Scholar 

  • Alavattam S, Glover ZK, Piros LN, Xiao N, Patel A, Kabakoff B (2012) Stability of IgG1 monoclonal antibodies in intravenous infusion bags under clinical in-use conditions. J Pham Sci 101(1):21–30

    Article  Google Scholar 

  • Alley SC, Benjamin DR, Jeffrey SC, Okeley NM, Meyer DL, Sanderson RJ, Senter PD (2008) Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem 19(3):759–765

    Article  CAS  PubMed  Google Scholar 

  • Baldwin AD, Kiick KL (2011) Tunable degradation of maleimide-thiol adducts in reducing environments. Bioconjugate Chem 22:1946–1953

    Article  CAS  Google Scholar 

  • Beckley NS, Lazzareschi KP, Chih H, Sharma VK, Flores HL (2013) Investigation into temperature-induced aggregation of an antibody drug conjugate. Bioconjugate Chem 24(10):1674–1683

    Article  CAS  Google Scholar 

  • Borisov OV, Ji JA, Wang YJ, Vega F, Ling VT (2011) Toward understanding molecular heterogeneity of polysorbates by application of liquid chromatography-mass spectrometry with computer-aided data analysis. Anal Chem 83:3934–3942

    Article  CAS  PubMed  Google Scholar 

  • Capasso S, Mazzarella L, Sica F, Zagari A, Salcadori S (1993) Kinetics and mechanism of succinimide ring formation in the deamidation process of asparagine residues. J Chem Soc Perkin Trans 2:679–682

    Article  Google Scholar 

  • Capasso S, Kirby AJ, Salvadori S, Zagari A (1995) Kinetics and mechanism of the reversible isomerization of aspartic acid residues in tetrapeptides. J Chem Soc Perkin Trans 2:437–442

    Article  Google Scholar 

  • Carpenter JF, Manning MC (eds) (2002) Rational design of stable protein formulations: theory and practice. Springer, New York

    Book  Google Scholar 

  • Carpenter JF, Kendrick BS, Chang BS, Manning MC, Randolph TW (1999) Inhibition of stress-induced aggregation of protein therapeutics. Methods Enzymol 309:236–255

    Article  CAS  PubMed  Google Scholar 

  • Challener CA (2014) Advances in linker technology: improving the safety and efficacy of antibody drug conjugates. http://www.biopharminternational.com. Accessed 1 Mar 2014

  • Chang BS, Kendrick BS, Carpenter JF (1996) Surface-induced denaturation of proteins during freezing and its inhibition by surfactants. J Pharm Sci 85:1325–1330

    Article  CAS  PubMed  Google Scholar 

  • Chang L, Shepherd DA, Sun J, Tang X, Pikal MJ (2005) Effect of sorbitol and residual moisture on the stability of lyophilized antibodies: implications for the mechanism of protein stabilization in the solid state. J Pharm Sci 94:1445–1455

    Article  CAS  PubMed  Google Scholar 

  • Chih HW, Gikanga B, Yang Y, Zhang B (2011) Identification of amino acid residues responsible†¨for the release of free drug from an antibody–drug conjugate utilizing lysine–succinimidyl ester chemistry. J Pharm Sci 100(7):2518–2525

    Article  CAS  PubMed  Google Scholar 

  • Ducry L (ed) (2013) Antibody-drug conjugates. Methods in molecular Biology, vol 1045. Humana New York

    Google Scholar 

  • Flygare JA, Pillow TH, Aristoff P (2013) Antibody-drug conjugates for the treatment of cancer. Chem Biol Drug Des 81:113–121

    Article  CAS  PubMed  Google Scholar 

  • Gieger T, Clarke S (1987) Deamidation, isomerization and racemization at asparaginyl and aspartyl residues in peptides. J Biol Chem 262:785–794

    Google Scholar 

  • Goswami S, Wang W, Arakawa T, Ohtake S (2013) Developments and Challenges for mAb-Based therapeutics. Antibodies 2:452–500

    Article  Google Scholar 

  • Ha E, Wang W, Wang YJ (2002) Peroxide formation in polysorbate 80 and protein stability. J Pharm Sci 91(10):2252–2264

    Article  CAS  PubMed  Google Scholar 

  • Harmon PA, Kosuda K, Nelson E, Mowery M, Reed RA (2006) A novel peroxy radical based oxidative stressing system for ranking the oxidizability of drug substances. J Pharm Sci 95(9):2014–2028

    Article  CAS  PubMed  Google Scholar 

  • Hovorka S, Schoneich C (2001) Oxidative degradation of pharmaceuticals: theory, mechanisms and inhibition. J Pharm Sci 90:253–269

    Article  CAS  PubMed  Google Scholar 

  • Ji AJ (2009) A novel stress model to study protein oxidation. Oral presentation at IBC the 4th Annual bioProcess international analytical & quality summit, San Diego 4–6 May, 2009

    Google Scholar 

  • Ji JA, Ingham E, Wang YJ (2009a) Effect of EDTA and methionine on preventing loss of viscosity of cellulose-based topical gel. AAPS Pharm Sci Tech 10(2):678–683

    Article  CAS  Google Scholar 

  • Ji JA, Zhang B, Cheng W, Wang YJ (2009b) Methionine, tryptophan, and histidine oxidation in a model protein, PTH: mechanisms and stabilization. J Pharm Sci 98:4485–4500

    Article  CAS  PubMed  Google Scholar 

  • Ji JA, Wang YJ, Zhang B (2010) Compositions and methods for the prevention of oxidative degradation of proteins. WO 2010030670 A 2, 2010

    Google Scholar 

  • Ji JA, Liu J, Wnag YJ (2013) Compositions and methods useful for stabilizing protein-containing formulations. WO2011119487 A3 May 2013

    Google Scholar 

  • Johnson R, Lewis L (2011) Freeze-drying protein formulations above their collapse temperatures: possible issues and concerns. Am Pharm Rev April 2011, vol 14 pp 50–54

    Google Scholar 

  • Junutula JR, Raab H, Clark S, Leipold DD, Weir S, Chen Y et al. (2008) Site-specific comjugation of a cytotoxid drug to an antibody improves the therapeutic index. Nat Biotechnol 26:925–932

    Article  CAS  PubMed  Google Scholar 

  • Junutula JR, Glagella KM, Graham RA, Parsons KI, Ha E, Raab H, Bhakta S, Nguyen T, Dugger DL, Li G, Mai E, Lewis PGD, Hiraragi H, Fuji RN, Tibbitts J, Vandlen R, Spencer SD, Scheller RH, Polakis P, Sliwkowski MX (2010) Engineered thio-trastuzumab–DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive beast cancer. Clin Cancer Res 16:4769–4778

    Article  CAS  PubMed  Google Scholar 

  • Kerwin BA (2008) Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci 97(8):2924–2935

    Article  CAS  PubMed  Google Scholar 

  • Kim SA (2009) Antibiotic-conjugated antibodies. US Patent 7569677 B2, 4 Aug 2009

    Google Scholar 

  • Kishore RS, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC (2011) The degradation of polysorbates 20 and 80 and its potential impact on the stability of biotherapeutics. Pharm Res 28(5):1194–2210

    Article  CAS  PubMed  Google Scholar 

  • Kreilgaard L, Frokjaer S, Flink JM, Randolph TW, Carpenter JF (1998) Effects of additives on the stability of recombinant human factor XIII during freeze-drying and storage in the dried solid. Archives Biochem Biophys 360:121–134

    Article  CAS  Google Scholar 

  • Kumru OS, Liu J, Ji JA, Cheng W, Wang YJ, Wang T, Joshi SB, Middaugh CR, Volkin DB (2012) Compatibility, physical stability, and characterization of an IgG4 monoclonal antibody after dilution into different intravenous administration bags. J Pharm Sci 101(10):3636–3650

    Article  CAS  PubMed  Google Scholar 

  • Labrenz SR (2014) Ester hydrolysis of polysorbate 80 in mAb drug product: evidence in support of the hypothesized risk after the observation of visible particulate in mAb formulations. J Pharm Sci. doi:10.1002/jps.24054

    Google Scholar 

  • Lam XM, Yang JY, Cleland JL (1997) Antioxidants for prevention of methionine oxidation in recombinant monoclonal antibody HER2. J Pharm Sci 86(11):1250–1255

    Article  CAS  PubMed  Google Scholar 

  • Li SH, Schoneich C, Borchardt RT (1995) Chemical instability of protein pharmaceuticals: mechanisms of oxidation and strategies for stabilization. Biotechnol Bioeng 48:490–500

    Article  CAS  PubMed  Google Scholar 

  • Lin D, Saleh S, Liebler DC (2008) Reversibility of covalent electrophile-protein adducts and chemical toxicity. Chem Res Toxicol 21(12):2361–2369

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu D, Ren D, Huang H, Dankberg J, Rosenfeld R et al. (2008a) Structure and stability changes of human IgG1 Fc as a consequence of methionine oxidation. Biochem 47:5088–5100

    Article  CAS  Google Scholar 

  • Liu H, Gaza-Bulseco G, Xiang T, Chumsae C (2008b) Structural effect of deglycosylation and methionine oxidation on a recombinant monoclonal antibody. Mol Immunol 45:701–708

    Article  CAS  PubMed  Google Scholar 

  • Luthra SA, Hodge IM, Utz M, Pikal MJ (2008) Correlation of annealing with chemical stability in lyophilized pharmaceutical glasses. J Pharm Sci 97:5240–5251

    Article  CAS  PubMed  Google Scholar 

  • Lyon RP, Doronina SO, Bovee TD (2013a) Self-stabilizing linker conjugates. WO Patent 2013173337 A2, 21 Nov 2013

    Google Scholar 

  • Lyon RP, Setter JR, Bovee TD, Doronina SO, Anderson ME, Balasubramanian B, Duniho S, Leiske CL, Senter PD (2013b) Self-stabilizing ADCs: conjugates prepared with maleimido drug-linkers that catalyze their own thiosuccinimide ring hydrolysis. Poste presented at American Association for Cancer Research, Washington DC. April 2013

    Google Scholar 

  • Lyon RP, Meyer DL, Setter JR, Senter PD (2012) Conjugation of anticancer drugs through endogenous monoclonal antibody cysteine residues. Methods Enzymol 502:123–138

    Article  CAS  PubMed  Google Scholar 

  • Maggio ET (2012) Polysorbates, peroxides, protein aggregation, and immunogenicity – a growing concern. J Excipients Food Chem 3(2):45–53

    CAS  Google Scholar 

  • Mather BD, Viswanathan K, Miller KM, Long TE (2006) Michael addition reactions in macromolecular design for emerging technologies. Prog Polym Sci 31:487–531

    Article  CAS  Google Scholar 

  • Naito K, Takeshita A, Shieno K, Nakamura S, Fujisawa S, Shinjo K, Yoshida H, Ohnishi K, Mori M, Terakawa S, Ohno R (2000) Calicheamicin-conjugated humanized antiCD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines. Leukemia 14: 1436–1443

    Article  CAS  PubMed  Google Scholar 

  • Nakajima Y, Suzuki S (2013) Environmental stresses induce misfolded protein aggregation in plant cells in a microtubule-dependent manner. Int J Mol Sci 14(4):7771–7783

    Article  PubMed Central  PubMed  Google Scholar 

  • Nema S, Washkuhn RJ, Brendel RJ (1997) Excipeints and their use in injectable products. PDA J Pharm Sci Tech 51:166–171

    CAS  Google Scholar 

  • Nguyen TH (1994) Oxidation degradation of protein pharmaceuticals, Chapter 4. In: Cleland JL, Langer R (eds) Formulation and delivery of protein and peptides. American Chemical Society, Washington, p 59–71

    Chapter  Google Scholar 

  • Nireesha GR, Divya L, Sowmya C, Venkateshan N, Babu MN, Lavakumar V (2013) Lyophilization/freeze drying – a review. Inter J Novel Trends in Pharm Sci 3(4):87–98

    Google Scholar 

  • Nolting B (2013) Linker technologies for antibody-drug conjugates. Methods Mol Biol 1045:71–100

    Article  PubMed  Google Scholar 

  • Oeswein OJ, Ongpipattanakul B, Shahrokh Z, Weissburg WS, Wong RP (1998) Stabilized antibody formulation. US Patent 2292730, 1998.

    Google Scholar 

  • Pace Al, Wong RL, Zhang TY, Kao Y, Wang YJ (2013) Asparagine deamidation dependence on buffer type, pH, and temperature. J Pharm Sci 102(6):1712–1723

    Article  CAS  PubMed  Google Scholar 

  • Panowksi S, Bhakta S, Raab H, Polakis P, Junutula J (2014) Site-specific antibody drug conjugates for cancer therapy. MAbs 6(1):34–45

    Article  PubMed Central  PubMed  Google Scholar 

  • Patel AR, Kulkarni S, Nandekar TD, Vavia PR (2008) Evaluation of alkyl polyglucoside as an alternative surfactant in the preparation of peptide-loaded nanoparticles. J Microencapsul 25(8):531–540

    Article  CAS  PubMed  Google Scholar 

  • Patel SM, Lobo B, Shah A (2013) Practical considerations for freeze-drying process design, development and scale-Up. http://www.americanpharmaceuticalreview.com. Accessed 25 Oct 2013

  • Pearlman R, Bewley TA (1993) Stability and characterization of human growth hormone. In: Wang YJ, Pearlman R (eds) Pharmaceutical biotechnology, vol. 5: formulation, characterization, and stability of protein drugs: case histories, Chapter 1. Plenum, New York, pp 1–58

    Google Scholar 

  • Phillip GDL, Li GM, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattelr WA, Lambert JM, Chari RVJ, Lutz RJ, Wong WLT, Jacobson FS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX (2008) Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 68: 9280–9290

    Article  Google Scholar 

  • Qi P, Volkin DB, Zhao H, Nedved ML, Hughes R, Bass R, Yi SC, Panek ME, Wang D, DalMonte P, Bond MD (2009) Characterization of the photodegradation of a human IgG1 monoclonal antibody formulated as a high-concentration liquid dosage form. J Pharm Sci 98(9):3117–3130

    Article  CAS  PubMed  Google Scholar 

  • Rey L, May J (eds) (2010) Freeze-drying/lyophilization of pharmaceutical and biological products, 3rd edn (Drugs and the pharmaceutical sciences). CRC New York

    Google Scholar 

  • Rosati S, Yang Y, Barendregt A, Heck JR (2014) Detailed mass analysis of structural heterogeneity in monoclonal antibodies using native mass spectrometry. Nature Protoc 9:967–976

    Article  CAS  Google Scholar 

  • Roy I, Gupta MN (2004) Freeze-drying of proteins: some emerging concerns. Biotechnol Appl Biochem 39(Pt 2):165–177

    Article  CAS  PubMed  Google Scholar 

  • Sasaoki K, Hiroshima T, Kusumoto S, Nishi K (1989) Oxidation of methionine residues of recombinant human interleukin 2 in aqueous solutions. Chem Pharm Bull (Tokyo) 37:2160–2164

    Article  CAS  Google Scholar 

  • Schneiderheinze J (2011) Analytical challenges in the analysis of peptide bioconjugates, WCBP, Washington DC, 9–11 Jan 2011

    Google Scholar 

  • Shen BQ et al. (2012) Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat Biotechnol 30:184–189

    Article  CAS  PubMed  Google Scholar 

  • Son K, Kwon C (1995) Stabilization of human epidermal growth factor (hEGF) in aqueous formulation. Pharm Res 12:451–454

    Article  CAS  PubMed  Google Scholar 

  • Steimann D, Ji AJ, Wang YJ, Schöneich C (2012) Oxidation of human growth hormone by oxygen-centered radicals: formation of Leu-101 hydroperoxide and Tyr-103 oxidation products. Mol Pharmaceutics 9(4):803–814

    Article  Google Scholar 

  • Stroop S, Conca D, Lundgard R, Renz M, Peabody L, Leigh S (2011) Photosensitizers form in histidine buffer and mediate the photodegradation of a monoclonal antibody. J Pharm Sci 100:5142–5155

    Article  CAS  PubMed  Google Scholar 

  • Teh LC, Murphy LJ, Hug NL, Surus AS, Friesen HG, Lazarus L, Chapman GE (1987) Methionine oxidation in human growth hormone and human chorionic somatomammotropin: effects on receptor binding and biological activities. J Biol Chem 262:6472–6477

    CAS  PubMed  Google Scholar 

  • Terrett J, Gangwar S, Rao-Naik C, Pan C, Guerlavais V, Huber M, Chong C, Green L, Cardarelli P, King D (2007) Single, low dose treatment of lymphoma and renal cancer xenografts with human anti-CD70 antibody-toxin conjugates, results in long term cures. In Proceedings of the 98th annual meeting of the American association for cancer research, Los Angeles, USA, 14–18 April 2007.

    Google Scholar 

  • Tse KF, Jeffers M, Pollack VA, McCabe DA, Shadish ML, Khramtsov NV, Hackett CS, Shenoy SG, Kuang B, Boldog FL, MacDougall JR, Bornstein G, Senter PD, Meyer DL, Lichenstein HS, LaRochelle WJ (2006) CR011, a fully human monoclonal antibody-auristatin E conjugate for the treatment of melanoma. Clin Cancer Res 12:1373–1382

    Article  CAS  PubMed  Google Scholar 

  • Tyler-Cross R, Schirch V (1991) Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. J Biol Chem 266:22549–22556

    CAS  PubMed  Google Scholar 

  • Valliere-Douglass JF, McFee WA, Salas-Solano O (2012) Native intact mass determination of antibodies conjugated with monomethyl Auristatin E and F at interchain cysteine residues. Anal Chem 84:2843–2849

    Article  CAS  PubMed  Google Scholar 

  • Wagner-Rousset E, Janin-Bussat MC, Colas O, Excoffier M, Ayoub D, Haeuw JF, Rilatt I, Perez M, Corvaïa N, Beck A (2014) Antibody-drug conjugate model fast characterization by LC-MS following IdeS proteolytic digestion. Mabs 6(1):173–184

    Article  PubMed Central  PubMed  Google Scholar 

  • Wakankar AA, Borchardt RT (2006) Formulation considerations for proteins susceptible to asparagine deamidation and aspartate isomerization. J Pharm Sci 95(11):2321–2336

    Article  CAS  PubMed  Google Scholar 

  • Wakankar AA, Feeney MB, Rivera J, Chen Y, Kim M, Sharma VK, Wang YJ (2010) Physicochemical stability of the antibody-drug conjugate trastuzumab-DM1: changes due to modification and conjugation processes. Bioconjugate Chem 21:1588–1595

    Article  CAS  Google Scholar 

  • Wang W (1999) Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm 185:129–188

    Article  CAS  PubMed  Google Scholar 

  • Wei Z, Feng J, Lin HY, Mullapudi S, Bishop E et al. (2007) Identification of a single tryptophan residue as critical for binding activity in a humanized monoclonal antibody against respiratory syncytial virus. Anal Chem 79:2797–2805

    Article  CAS  PubMed  Google Scholar 

  • Xu K, Liu L, Saad OM, Baudys J, Williams L, Leipold D, Shen B, Raab H, Junutula JR, Kim A, Kaur S (2011) Characterization of intact antibody-drug conjugates from plasma/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry. Anal Biochem 412(1):56–66

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Anchordoquy J (2009) Effects of moisture content on the storage stability of dried lipoplex formulations. J Pharm Sci 98(9):3278–3289

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao F, Ghezzo-Schoneich E, Aced GI, Hong J, Milby T, Schöneich C (1997) Metal-catalyzed oxidation of histidine in human growth hormone: Mechanism, isotope effects, and inhibition by a mild denaturing alcohol. J Biol Chem 272:9019–9029

    Article  CAS  PubMed  Google Scholar 

  • Zheng K, Ren D, Lilyestrom W, Gokarn Y, Bayer R, Scherer T, Wang YJ, Ji JA (2012) AAPH induced mAb oxidation and aggregation. Poster presented at the 243rd ACS national meeting, San Diego, 25–29 March 2012

    Google Scholar 

  • Zheng K, Chen Y, Wang YJ, Zheng L, Hutchinson M, Gorrell J, Liu J, Ji AJ (2013) Characterization of ring-opening reaction of thio-succinimide linker in ADC, San Antonio, Texas, Presented at AAPS annual meeting and Exposition, 10–14 Nov 2013

    Google Scholar 

Download references

Acknowledgments

We thank Dr. Jamie Moore, Dr. Dana Anderson, Dr. Sreedhara Alavattam, Dr. Kai Zheng, and Dr. Lynn Gennaro for their comments and help in preparing this book chapter.

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  1. Late Stage Pharmaceutical Development, Genentech, South San Francisco, CA, USA

    Junyan A. Ji, Jun Liu & Y. John Wang

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  1. Junyan A. Ji
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  2. Jun Liu
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Correspondence to Junyan A. Ji .

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Editors and Affiliations

  1. Western University of Health Sciences, Department of Pharmaceutical Sciences, Pomona, California, USA

    Jeffrey Wang

  2. University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, California, USA

    Wei-Chiang Shen

  3. University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, California, USA

    Jennica L. Zaro

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Ji, J., Liu, J., Wang, Y. (2015). Formulation Development for Antibody-Drug Conjugates. In: Wang, J., Shen, WC., Zaro, J. (eds) Antibody-Drug Conjugates. AAPS Advances in the Pharmaceutical Sciences Series, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-13081-1_5

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