Jindrich Kopecek

Jindrich Kopecek, PhD, DSc

Languages spoken: Czech, German, Russian, English

Academic Information

Departments Primary - Medicinal Chemistry

Research Interests

  • Drug Delivery Systems
  • Biodegradability of Polymers
  • Genetically Engineered Materials
  • Biorecognition of Macromolecules
  • Bioconjugate Chemistry

Jindrich Kopecek, PhD, DSc, is a distinguished professor in the Departments of Pharmaceutics, Pharmaceutical Chemistry, and Bioengineering at the University of Utah. He is also a member of the Experimental Therapeutics Program at Huntsman Cancer Institute.

Kopecek's research interests include the design, synthesis, and characterization of biorecognizable biomedical polymers. He focuses on the development of targeted anticancer drugs, particularly to treat ovarian cancer.

Kopecek received a master's degree from the Institute of Chemical Technology, Czechoslovakia, a PhD from the Institute of Macromolecular Chemistry, Czechoslovakia, and a DSc from the Czechoslovak Academy of Sciences.

Research Statement

Research in the Kopeček Biomedical Polymers Laboratory focuses on two main areas:

Macromolecular therapeutics. Recent research focuses on the design of backbone degradable, long-circulating polymer carriers that contain enzymatically degradable oligopeptide sequences in the main chain. These N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug (epirubicin, gemcitabine, paclitaxel) conjugates have demonstrated enhanced efficacy in the treatment of animal tumor models when compared to non-degradable HPMA copolymer conjugates or free drugs. Combination therapy targeting both tumor-initiating and differentiated cancer cell populations is also studied.

Drug-free macromolecular therapeutics. A new therapeutic approach for the treatment of B cell malignancies has been developed.The effectiveness of the new system is based on biorecognition events without the participation of low molecular weight drugs. Apoptosis of cells can be initiated by the biorecognition of complementary peptide/oligonucleotide motifs at the cell surface resulting in the crosslinking of slowly internalizing receptors. Drug-free macromolecular therapeutics (DFMT) are composed from two nanoconjugates: 1) bispecific engager, Fab’-MOTIF1 (anti-CD20 Fab’ fragment conjugated with coiled-coil forming peptide or morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MOTIF2)X (HPMA copolymer or human serum albumin grafted with multiple copies of complementary oligopeptide or morpholino oligonucleotide).The efficacy of the system was validated in vitro, in vivo and on cells isolated from patients with various subtypes of B cell malignancies.

Education History

Doctoral Training Czechoslovak Academy of Sciences
 DSc
Postdoctoral Fellowship National Research Council of Canada
 Postdoctoral Fellow
Doctoral Training Czechoslovak Academy of Sciences
 PhD
Graduate Training Institute of Chemical Technology
 MS

Selected Publications

Journal Article

  1. Wang J, Li L, Yang J, Clair PM, Glenn MJ, Stephens DM, Radford DC, Kosak KM, Deininger MW, Shami PJ, Kopeek J (2019). Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine. Nanomedicine, 16, 217-225. (Read full article)
  2. Li L, Yang J, Soodvilai S, Wang J, Opanasopit P, Kopeek J (2018). Drug-free albumin-triggered sensitization of cancer cells to anticancer drugs. J Control Release, 293, 84-93. (Read full article)
  3. Li L, Yang J, Wang J, Kopeek J (2018). Drug-free macromolecular therapeutics exhibit amplified apoptosis in G2/M phase arrested cells. J Drug Target, 27(5-6), 566-572. (Read full article)
  4. Yang J, Li L, Kopeek J (2018). Biorecognition: A key to drug-free macromolecular therapeutics. Biomaterials, 190-191, 11-23. (Read full article)
  5. Zhang L, Fang Y, Li L, Yang J, Radford DC, Kopeek J (2018). Human Serum Albumin-Based Drug-Free Macromolecular Therapeutics: Apoptosis Induction by Coiled-Coil-Mediated Cross-Linking of CD20 Antigens on Lymphoma B Cell Surface. Macromol Biosci, 18(11), e1800224. (Read full article)
  6. Li L, Yang J, Wang J, Kopeek J (2017). Drug-Free Macromolecular Therapeutics Induce Apoptosis via Calcium Influx and Mitochondrial Signaling Pathway. Macromol Biosci, 18(1). (Read full article)
  7. Zhang L, Fang Y, Yang J, Kopeek J (2016). Drug-free macromolecular therapeutics: Impact of structure on induction of apoptosis in Raji B cells. J Control Release, 263, 139-150. (Read full article)
  8. Yang J, Kopeek J (2017). The Light at the End of the Tunnel-Second Generation HPMA Conjugates for Cancer Treatment. Curr Opin Colloid Interface Sci, 31, 30-42. (Read full article)
  9. Zhang L, Fang Y, Kopeek J, Yang J (2017). A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin's lymphomas. Eur J Pharm Sci, 103, 36-46. (Read full article)
  10. Pelaz B, Alexiou C, Alvarez-Puebla RA, Alves F, Andrews AM, Ashraf S, Balogh LP, Ballerini L, Bestetti A, Brendel C, Bosi S, Carril M, Chan WC, Chen C, Chen X, Chen X, Cheng Z, Cui D, Du J, Dullin C, Escudero A, Feliu N, Gao M, George M, Gogotsi Y, Grnweller A, Gu Z, Halas NJ, Hampp N, Hartmann RK, Hersam MC, Hunziker P, Jian J, Jiang X, Jungebluth P, Kadhiresan P, Kataoka K, Khademhosseini A, Kopeek J, Kotov NA, Krug HF, Lee DS, Lehr CM, Leong KW, Liang XJ, Ling Lim M, Liz-Marzn LM, Ma X, Macchiarini P, Meng H, Mhwald H, Mulvaney P, Nel AE, Nie S, Nordlander P, Okano T, Oliveira J, Park TH, Penner RM, Prato M, Puntes V, Rotello VM, Samarakoon A, Schaak RE, Shen Y, Sjqvist S, Skirtach AG, Soliman MG, Stevens MM, Sung HW, Tang BZ, Tietze R, Udugama BN, VanEpps JS, Weil T, Weiss PS, Willner I, Wu Y, Yang L, Yue Z, Zhang Q, Zhang Q, Zhang XE, Zhao Y, Zhou X, Parak WJ (2017). Diverse Applications of Nanomedicine. ACS Nano, 11(3), 2313-2381. (Read full article)
  11. Low SA, Galliford CV, Jones-Hall YL, Roy J, Yang J, Low PS, Kopeek J (2017). Healing efficacy of fracture-targeted GSK3β inhibitor-loaded micelles for improved fracture repair. Nanomedicine (Lond), 12(3), 185-193. (Read full article)
  12. Zhang R, Yang J, Radford DC, Fang Y, Kopeek J (2016). FRET Imaging of Enzyme-Responsive HPMA Copolymer Conjugate. Macromol Biosci, 17(1). (Read full article)
  13. Yang J, Kopeek J (2015). Design of smart HPMA copolymer-based nanomedicines. J Control Release, 240, 9-23. (Read full article)
  14. Zhang L, Zhang R, Yang J, Wang J, Kopeek J (2016). Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate. J Control Release, 235, 306-318. (Read full article)
  15. Hartley JM, Zhang R, Gudheti M, Yang J, Kopeek J (2016). Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM. J Control Release, 231, 50-9. (Read full article)
  16. Chu TW, Feng J, Yang J, Kopeek J (2015). Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation. J Control Release, 220(Pt B), 608-16. (Read full article)
  17. Yang J, Kopeek J (2015). POLYMERIC BIOMATERIALS AND NANOMEDICINES. J Drug Deliv Sci Technol, 30(Pt B), 318-330. (Read full article)
  18. Yang J, Zhang R, Radford DC, Kopeek J (2015). FRET-trackable biodegradable HPMA copolymer-epirubicin conjugates for ovarian carcinoma therapy. J Control Release, 218, 36-44. (Read full article)
  19. Yang J, Zhang R, Christopher Radford D, Kopeek J (2015). Design and synthesis of FRET-trackable HPMA-based biodegradable conjugates for drug/gene delivery. J Control Release, 213, e58. (Read full article)
  20. Hartley JM, Chu TW, Peterson EM, Zhang R, Yang J, Harris J, Kopeek J (2015). Super-Resolution Imaging and Quantitative Analysis of Membrane Protein/Lipid Raft Clustering Mediated by Cell-Surface Self-Assembly of Hybrid Nanoconjugates. Chembiochem, 16(12), 1725-9. (Read full article)
  21. Peng ZH, Kopeek J (2015). Enhancing Accumulation and Penetration of HPMA Copolymer-Doxorubicin Conjugates in 2D and 3D Prostate Cancer Cells via iRGD Conjugation with an MMP-2 Cleavable Spacer. J Am Chem Soc, 137(21), 6726-9. (Read full article)
  22. Zhang R, Yang J, Chu TW, Hartley JM, Kopeek J (2015). Multimodality imaging of coiled-coil mediated self-assembly in a "drug-free" therapeutic system. Adv Healthc Mater, 4(7), 1054-65. (Read full article)
  23. Zhou Y, Yang J, Zhang R, Kopeek J (2014). Combination therapy of prostate cancer with HPMA copolymer conjugates containing PI3K/mTOR inhibitor and docetaxel. Eur J Pharm Biopharm, 89, 107-15. (Read full article)
  24. Peng ZH, Kopeek J (2014). HPMA Copolymer CXCR4 Antagonist Conjugates Substantially Inhibited the Migration of Prostate Cancer Cells. ACS Macro Lett, 3(12), 1240-1243. (Read full article)
  25. Chu TW, Kosak KM, Shami PJ, Kopeek J (2015). Drug-free macromolecular therapeutics induce apoptosis of patient chronic lymphocytic leukemia cells. Drug Deliv Transl Res, 4(5-6), 389-94. (Read full article)
  26. Low SA, Yang J, Kopeek J (2014). Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics. Bioconjug Chem, 25(11), 2012-20. (Read full article)
  27. Zhang R, Yang J, Sima M, Zhou Y, Kopeek J (2014). Sequential combination therapy of ovarian cancer with degradable N-(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates. Proc Natl Acad Sci U S A, 111(33), 12181-6. (Read full article)
  28. Duangjai A, Luo K, Zhou Y, Yang J, Kopeek J (2013). Combination cytotoxicity of backbone degradable HPMA copolymer gemcitabine and platinum conjugates toward human ovarian carcinoma cells. Eur J Pharm Biopharm, 87(1), 187-96. (Read full article)
  29. Kopeek J, Stanwix H (2014). Interview with Professor Jindřich Kopeček. Nanomedicine (Lond), 9(5), 577-9. (Read full article)
  30. Chu TW, Yang J, Zhang R, Sima M, Kopeek J (2013). Cell surface self-assembly of hybrid nanoconjugates via oligonucleotide hybridization induces apoptosis. ACS Nano, 8(1), 719-30. (Read full article)
  31. Zhou Y, Yang J, Rhim JS, Kopeek J (2013). HPMA copolymer-based combination therapy toxic to both prostate cancer stem/progenitor cells and differentiated cells induces durable anti-tumor effects. J Control Release, 172(3), 946-53. (Read full article)
  32. Larson N, Yang J, Ray A, Cheney DL, Ghandehari H, Kopeek J (2013). Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment. Int J Pharm, 454(1), 435-43. (Read full article)
  33. Zhang R, Luo K, Yang J, Sima M, Sun Y, Jant-Amsbury MM, Kopeek J (2012). Synthesis and evaluation of a backbone biodegradable multiblock HPMA copolymer nanocarrier for the systemic delivery of paclitaxel. J Control Release, 166(1), 66-74. (Read full article)
  34. Pan H, Sima M, Yang J, Kopeek J (2013). Synthesis of long-circulating, backbone degradable HPMA copolymer-doxorubicin conjugates and evaluation of molecular-weight-dependent antitumor efficacy. Macromol Biosci, 13(2), 155-60. (Read full article)
  35. Zhou Y, Kopeek J (2012). Biological rationale for the design of polymeric anti-cancer nanomedicines. J Drug Target, 21(1), 1-26. (Read full article)
  36. Kopeek J (2012). Polymer-drug conjugates: origins, progress to date and future directions. Adv Drug Deliv Rev, 65(1), 49-59. (Read full article)
  37. Low SA, Kopeek J (2012). Targeting polymer therapeutics to bone. Adv Drug Deliv Rev, 64(12), 1189-204. (Read full article)
  38. Kopeek J, Yang J (2012). Smart self-assembled hybrid hydrogel biomaterials. Angew Chem Int Ed Engl, 51(30), 7396-417. (Read full article)
  39. Fowers KD, Kopeek J (2012). Targeting of multidrug-resistant human ovarian carcinoma cells with anti-P-glycoprotein antibody conjugates. Macromol Biosci, 12(4), 502-14. (Read full article)
  40. Johnson RN, Kopekov P, Kopeek J (2012). Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates. Biomacromolecules, 13(3), 727-35. (Read full article)
  41. Liu J, Kopekov P, Pan H, Sima M, Bhler P, Wolf P, Elssser-Beile U, Kopeek J (2012). Prostate-cancer-targeted N-(2-hydroxypropyl)methacrylamide copolymer/docetaxel conjugates. Macromol Biosci, 12(3), 412-22. (Read full article)
  42. Zhou Y, Yang J, Kopeek J (2011). Selective inhibitory effect of HPMA copolymer-cyclopamine conjugate on prostate cancer stem cells. Biomaterials, 33(6), 1863-72. (Read full article)
  43. Krimmer SG, Pan H, Liu J, Yang J, Kopeek J (2011). Synthesis and characterization of poly(ε-caprolactone)-block-poly[N-(2-hydroxypropyl)methacrylamide] micelles for drug delivery. Macromol Biosci, 11(8), 1041-51. (Read full article)
  44. Wu LC, Yang J, Kopeek J (2011). Hybrid hydrogels self-assembled from graft copolymers containing complementary β-sheets as hydroxyapatite nucleation scaffolds. Biomaterials, 32(23), 5341-53. (Read full article)
  45. Luo K, Yang J, Kopekov P, Kopeek J (2011). Biodegradable Multiblock Poly[N-(2-hydroxypropyl)methacrylamide] via Reversible Addition-Fragmentation Chain Transfer Polymerization and Click Chemistry. Macromolecules, 44(8), 2481-2488. (Read full article)
  46. Yang J, Luo K, Pan H, Kopekov P, Kopeek J (2011). Synthesis of Biodegradable Multiblock Copolymers by Click Coupling of RAFT-Generated HeterotelechelicPolyHPMA Conjugates. React Funct Polym, 71(3), 294-302. (Read full article)
  47. Pan H, Yang J, Kopeckov P, Kopecek J (2010). Backbone degradable multiblock N-(2-hydroxypropyl)methacrylamide copolymer conjugates via reversible addition-fragmentation chain transfer polymerization and thiol-ene coupling reaction. Biomacromolecules, 12(1), 247-52. (Read full article)
  48. Kopecek J (2010). Biomaterials and drug delivery: past, present, and future. Mol Pharm, 7(4), 922-5. (Read full article)
  49. Yang J, Jacobsen MT, Pan H, Kopecek J (2010). Synthesis and characterization of enzymatically degradable PEG-based peptide-containing hydrogels. Macromol Biosci, 10(4), 445-54. (Read full article)
  50. Liu J, Bauer H, Callahan J, Kopeckov P, Pan H, Kopecek J (2010). Endocytic uptake of a large array of HPMA copolymers: Elucidation into the dependence on the physicochemical characteristics. J Control Release, 143(1), 71-9. (Read full article)
  51. Wu K, Liu J, Johnson RN, Yang J, Kopecek J (2010). Drug-free macromolecular therapeutics: induction of apoptosis by coiled-coil-mediated cross-linking of antigens on the cell surface. Angew Chem Int Ed Engl, 49(8), 1451-5. (Read full article)
  52. Kopeek J (2009). HYDROGELS FROM SOFT CONTACT LENSES AND IMPLANTS TO SELF-ASSEMBLED NANOMATERIALS. J Polym Sci A Polym Chem, 47(22), 5929-5946. (Read full article)
  53. Gao SQ, Sun Y, Kopeckov P, Peterson CM, Kopecek J (2009). Antitumor efficacy of colon-specific HPMA copolymer/9-aminocamptothecin conjugates in mice bearing human-colon carcinoma xenografts. Macromol Biosci, 9(11), 1135-42. (Read full article)
  54. Sheparovych R, Roiter Y, Yang J, Kopeek J, Minko S (2009). Stimuli-responsive properties of peptide-based copolymers studied via directional growth of self-assembled patterns on solid substrate. Biomacromolecules, 10(7), 1955-61. (Read full article)
  55. Callahan J, Kopekov P, Kopeek J (2009). Intracellular trafficking and subcellular distribution of a large array of HPMA copolymers. Biomacromolecules, 10(7), 1704-14. (Read full article)
  56. Duek K, Dukov-Smrkov M, Yang J, Kopeek J (2010). Coiled-Coil Hydrogels. Effect of Grafted Copolymer Composition and Cyclization on Gelation. Macromolecules, 42(6), 2265-2274. (Read full article)
  57. Kopecek J, Yang J (2008). Peptide-directed self-assembly of hydrogels. Acta Biomater, 5(3), 805-16. (Read full article)
  58. Johnson RN, Kopeckov P, Kopecek J (2009). Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20. Bioconjug Chem, 20(1), 129-37. (Read full article)
  59. Segal E, Pan H, Ofek P, Udagawa T, Kopeckov P, Kopecek J, Satchi-Fainaro R (2009). Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS One, 4(4), e5233. (Read full article)
  60. Yuan W, Yang J, Kopeckov P, Kopecek J (2008). Smart hydrogels containing adenylate kinase: translating substrate recognition into macroscopic motion. J Am Chem Soc, 130(47), 15760-1. (Read full article)
  61. Hongrapipat J, Kopeckov P, Liu J, Prakongpan S, Kopecek J (2008). Combination chemotherapy and photodynamic therapy with fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells. Mol Pharm, 5(5), 696-709. (Read full article)
  62. Pan H, Liu J, Dong Y, Sima M, Kopeckov P, Brandi ML, Kopecek J (2008). Release of prostaglandin E(1) from N-(2-hydroxypropyl)methacrylamide copolymer conjugates by bone cells. Macromol Biosci, 8(7), 599-605. (Read full article)
  63. Pan H, Sima M, Kopeckov P, Wu K, Gao S, Liu J, Wang D, Miller SC, Kopecek J (2008). Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates. Mol Pharm, 5(4), 548-58. (Read full article)
  64. Cuchelkar V, Kopeckov P, Kopecek J (2008). Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates. Macromol Biosci, 8(5), 375-83. (Read full article)
  65. Hongrapipat J, Kopeckov P, Prakongpan S, Kopecek J (2007). Enhanced antitumor activity of combinations of free and HPMA copolymer-bound drugs. Int J Pharm, 351(1-2), 259-70. (Read full article)
  66. Xu C, Kopecek J (2007). Genetically engineered block copolymers: influence of the length and structure of the coiled-coil blocks on hydrogel self-assembly. Pharm Res, 25(3), 674-82. (Read full article)
  67. Yang J, Wu K, Konk C, Kopecek J (2008). Dynamic light scattering study of self-assembly of HPMA hybrid graft copolymers. Biomacromolecules, 9(2), 510-7. (Read full article)
  68. Malugin A, Kopeckov P, Kopecek J (2007). Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells. J Control Release, 124(1-2), 6-10. (Read full article)
  69. Kopecek J (2007). Hydrogel biomaterials: a smart future? Biomaterials, 28(34), 5185-92. (Read full article)
  70. Pan H, Kopeckov P, Liu J, Wang D, Miller SC, Kopecek J (2007). Stability in plasmas of various species of HPMA copolymer-PGE1 conjugates. Pharm Res, 24(12), 2270-80. (Read full article)
  71. Wang D, Miller SC, Shlyakhtenko LS, Portillo AM, Liu XM, Papangkorn K, Kopeckov P, Lyubchenko Y, Higuchi WI, Kopecek J (2007). Osteotropic Peptide that differentiates functional domains of the skeleton. Bioconjug Chem, 18(5), 1375-8. (Read full article)
  72. Ding H, Kopeckov P, Kopecek J (2007). Self-association properties of HPMA copolymers containing an amphipathic heptapeptide. J Drug Target, 15(7-8), 465-74. (Read full article)
  73. Shiah JG, Konk C, Spikes JD, Kopecek J (2009). Influence of pH on aggregation and photoproperties of n-(2-hydroxypropyl)methacrylamide copolymer-meso-chlorin e6 conjugates. Drug Deliv, 5(2), 119-26. (Read full article)

Patent

  1. Kopecek J, et al (1995). Colonic-targeted oral drug-dosage forms based on crosslinked hydrogels containing azobonds and exhibiting pH-dependent swelling. U.S. Patent No. 5,415,864. Washington, D.C.:U.S. Patent and Trademark Office.
  2. Kopecek J, et al (1993). Drug delivery system for the simultaneous delivery of drugs activatable by enzymes and light. U.S. Patent No. 5,258,453. Washington, D.C.:U.S. Patent and Trademark Office.
  3. Kopecek J, et al (1991). Synthetic polymeric drugs. U.S. Patent No. 5,037,883. Washington, D.C.:U.S. Patent and Trademark Office.
  4. Andrade, Kopecek J, et al (1991). Polymer supersurfactants for protein resistance and protein removal. U.S. Patent No. 5,075,400. Washington, D.C.:U.S. Patent and Trademark Office.
  5. Lim, Kopecek J, et al (1978). Hydrophilic N,N-diethyl acrylamide copolymers. U.S. Patent No. 4,074,039. Washington, D.C.:U.S. Patent and Trademark Office.
  6. Drobnik, Kopecek J, et al (1978). Preparation of biogically active substances bearing -NH2 groups in a form releasable by enzymatic cleavage. U.S. Patent No. 4,097,470. Washington, D.C.:U.S. Patent and Trademark Office.
  7. Kopecek J, et al (1976). Copolymers based on N-substituted acrylamides, N-substituted methacrylamides and N,N-disubstituted acrylamides and the method of their manufacturing. U.S. Patent No. 4,062,831. Washington, D.C.:U.S. Patent and Trademark Office.
  8. Kopecek J, et al (1976). Soluble hydrophilic polymers and process for processing the same. U.S. Patent No. 3,997,660. Washington, D.C.:U.S. Patent and Trademark Office.
  9. Lim, Kopecek J, et al (1976). Infusion solutions and method of manufacturing same. U.S. Patent No. 3,997,660. Washington, D.C.:U.S. Patent and Trademark Office.
  10. Kopecek J, et al (1976). Soluble hydrophilic polymers and process for processing the same. U.S. Patent No. 3,931,111. Washington, D.C.:U.S. Patent and Trademark Office.
  11. Vacik, Kopecek J (1976). Hydrophilic nitrite copolymers. U.S. Patent No. 3,931,123. Washington, D.C.:U.S. Patent and Trademark Office.
  12. Lim, Kopecek J, et al (1975). Method for producing of articles from hydrophilic polymers appropriate for repeated or long-term contact with living tissue or mucous membrane. U.S. Patent No. 3,876,594. Washington, D.C.:U.S. Patent and Trademark Office.
  13. Lim, Kopecek J, et al (1973). Device for connecting or joining the ends of interrupted tubular organs in surgical operations without stiching. U.S. Patent No. 3,774,615. Washington, D.C.:U.S. Patent and Trademark Office.
  14. Lim, Kopecek J, et al (1973). Method of hydrophilization of transparent objects made of hydrophobic organic polymers. U.S. Patent No. 3,745,042. Washington, D.C.:U.S. Patent and Trademark Office.
  15. Kopecek J, et al (1970). Increasing permeability of reverse osmosis membranes. U.S. Patent No. 3,536,612. Washington, D.C.:U.S. Patent and Trademark Office.