Antibodies and methods for treating rabies virus infection

Abstract

The name of the invention is antibodies and methods for the treatment of rabies virus infection. The present invention provides antibodies and antigen-binding fragments thereof that strongly neutralize rabies virus infection and uses of such antibodies. In particular, the present invention provides methods of treating rabies virus infections, such as rabies.

Description

[0001] This application is a divisional application. The filing date of the original application is October 18, 2019, and the application number is 2019800842566

[0002] (PCT / EP2019 / 078439), entitled “Antibodies and methods for treating lyssavirus infections”.

[0003] The present invention relates to antibodies and antigen-binding fragments thereof that potently neutralize lyssavirus infection, and to uses of such antibodies. In particular, the present invention relates to the treatment of lyssavirus infection (such as rabies).

[0004] Rabies is a viral infection that causes acute inflammation of the brain. Therefore, rabies is a neurotropic viral disease. Rabies is distributed almost worldwide and is usually transmitted to humans by bites of infected wild or domestic animals, resulting in a devastating disease that is almost 100% fatal in individuals who do not receive post-exposure prophylaxis (PEP). Although rabies can be prevented with PEP, there is no effective cure after the onset of symptoms (Manning SE, Rupprecht CE, Fishbein D, Recommend CHM, 2008. Human rabies prevention-United states, 2008; Dacheux L, Delmas O, Bourhy H. Human rabies encephalitis prevention and treatment: progress since Pasteur's discovery. Infect Disord Drug Targets. 2011 Jun; 11(3): 251-99). Even with advanced supportive care, the mortality rate is still close to 100% (Brett W. Petersen and Charles E. Rupprecht, 2011. Human Rabies Epidemiology and Diagnosis, Non-Flavivirus Encephalitis, Dr. Sergey Tkachev (Ed.), InTech, DOI: 10.5772 / 21708).Therefore, management approaches often focus on mitigation (Jackson AC, Warrell MJ, Rupprecht CE, Ertl HCJ, Dietzschold B, O'Reilly M, Leach RP, Fu ZF, Wunner WH, Bleck TP, Wilde H. 2003. Management of rabies in humans. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 36:60–63; Tarantola A, Crabol Y, Mahendra BJ, In S, Barennes H, Bourhy H, Peng Y, Ly S, Buchy P. Caring for patients with rabies in developing countries—the neglected importance of palliative care. Trop Med Int Health. 2016 Apr; 21(4):564-7).

[0005] Early symptoms of rabies may include fever, anorexia, nausea, local pain at the bite site, restlessness, and depression. These symptoms are followed by one or more of the following symptoms: vigorous exercise, uncontrolled excitement, fear of water, fear of heights, confusion, hyperactivity, inability to move body parts, paralysis, and loss of consciousness. After the onset of symptoms, rabies almost always leads to death. The time from infection to the onset of symptoms can vary from less than a week to more than a year. The timeframe generally depends on the distance the virus must travel to reach the central nervous system (Ugolini G, Hemachudha T. Rabies: changing prophylaxis and new insights in pathophysiology. Curr Opin Infect Dis. 2018 Feb; 31 (1): 93-101).

[0006] Rabies is widespread worldwide, with approximately 15 to 29 million people treated annually after exposure to rabies, usually through bites from infected animals (dogs, bats, foxes, cats, monkeys, raccoons, skunks, cattle, wolves, coyotes, and other domestic and wild animals). An estimated 40,000 to 70,000 people die from the disease each year, primarily in Africa, China, and India, and 50% of rabies cases worldwide occur in children. These data highlight the significant unmet medical need for safe, effective, and affordable rabies treatments (Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, Costa P, Freuling CM, Hiby E, Knopf L, Leanes F, Meslin FX, Metlin A, Miranda ME, Müller T, Nel LH, Recuenco S, Rupprecht CE, Schumacher C, Taylor L, Vigilato MA, Zinsstag J, Dushoff J; Global Alliance for Rabies Control Partners for Rabies Prevention. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015 Apr 16;9(4):e0003709).

[0007] Rabies prevention can be achieved through pre-exposure or post-exposure vaccination, most often using modern tissue culture-based vaccines. For high-risk groups, pre-exposure immunization (pre-exposure prophylaxis (PrEP)) is recommended, and this immunization is achieved through the administration of rabies vaccines (active immunization). High-risk groups include people who work with bats or spend extended periods of time in areas of the world where rabies is common. In addition, anti-rabies vaccines are recommended for people traveling to African and Asian countries where rabies is endemic.

[0008] Currently available human rabies vaccines primarily include broad-spectrum inactivated vaccines, while live attenuated vaccines are still used for wildlife vaccination. Human vaccines primarily include human diploid cell vaccine (HDCV), chicken embryo cell vaccine (PCEC), and African green monkey kidney cell line vaccine. New vaccines are under development and include recombinant vaccines, DNA vaccines, and RNA vaccines (Alberer M, Gnad-Vogt U, Hong HS, Mehr KT, Backert L, Finak G, Gottardo R, Bica MA, Garofano A, Koch SD, Fotin-Mleczek M, Hoerr I, Clemens R, Sonnenburg von F, 2017. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomized, prospective, first-in-human phase 1 clinical trial. Lancet 390:1511–1520).

[0009] Following exposure to the virus, post-exposure prophylaxis (PEP) with rabies vaccine and rabies immune globulin (RIG) is the standard treatment for preventing the disease if a person receives treatment as soon as possible after infection, i.e., during the first few days after infection. If left untreated until symptoms begin, rabies is almost 100% fatal. Thus, currently, there is no therapeutic treatment for rabies.

[0010] Therefore, when assuming that someone is infected by lyssavirus, post-exposure prophylaxis (PEP) is given as " standard treatment ", it is with rabies immunoglobulin (RIG)---particularly, people or horse rabies immunoglobulin (being respectively HRIG and ERIG)---and rabies vaccine combination.Particularly, according to the information of rabies vaccine manufacturer, the patient receives the RIG (passive immunization) of a dosage and the rabies vaccine (active immunization) of several dosage.In widely used standard therapy, for example, the vaccine of five dosages is given in the period of 28 days, namely the rabies vaccine of first dosage is given as soon as possible after exposure, preferably during the 0th day, other dosage is given during the 3rd, 7th, 14th and 28th day after the first dosage (see http: / / www.rki.de / DE / Content / Infekt / EpidBull / Merkblaetter / Ratgeber_Tollwut.html, retrieved on November 12, 2014). Recently, these recommendations have been revised, and a shorter course of vaccine administration is being promoted (Rabies vaccines: WHO position paper – April 2018. Editor: Dr B. AbelaRidder / Neglected Zoonotic Diseases. Page: 18. Publication date: April 20, 2018. WHO Reference Number: No 16, 2018, 93, 201–220). In contrast, rabies immune globulin (RIG) for passive immunization is given only once, preferably at the start of post-exposure vaccination, or as soon as possible thereafter. The dose of human rabies immune globulin (HRIG) proposed by WHO is 20 IU / kg body weight; for equine immune globulin (ERIG) and F(ab')2 products, it is 40 IU / kg body weight (see http: / / www.who.int / rabies / human / WHO_strategy_prepost_exposure / en / index1.html#, retrieved on November 12, 2014). Higher doses may reduce vaccine efficacy. All rabies immune globulin, or immune globulin that avoids possible compartment syndrome as much as possible anatomically, should be administered into or around the site of trauma (one or more). The remaining immune globulin, if any, should be injected intramuscularly at a site away from the site of vaccine administration. Rabies immune globulin can be diluted to a volume sufficient to effectively and safely infiltrate all wounds (see http: / / www.who.int / rabies / human / WHO_strategy_prepost_exposure / en / index1.html#, retrieved on November 12, 2014).If given up to 24-48 hours after exposure, this is usually successful. HRIG is widely used, especially in developed countries, and is considered safer than ERIG. The high cost of HRIG and its limited availability have prevented its widespread use in developing countries. In addition, vaccines and HRIG or ERIG do not effectively protect against infection from different lyssavirus species (protection is negatively correlated with the genetic distance of the vaccine strain).

[0011] Several attempts have been made to treat symptomatic rabies. In 2004, a young patient from Wisconsin survived rabies with a treatment regimen known as the "Milwaukee protocol" (Willoughby RE, Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, Chusid MJ, Rupprecht CE. 2005. Survival after treatment of rabies with induction of coma. N Engl J Med 352:2508–2514). The Milwaukee protocol is a rabies treatment plan that focuses on therapeutic coma and the use of N-methyl D-aspartate (NMDA) receptor antagonists. Since the case report was published in 2005, the protocol has been revised four times to reach its current version, including therapeutic coma, ketamine infusion, amantadine, and screening / prevention / management of cerebral vasospasm. Critics of the Milwaukee protocol have expressed concern about its lack of efficacy in human rabies, with at least 31 failures reported in the literature to date (Zeiler FA, Jackson AC. 2016. Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned. Can J Neurol Sci 43:44–51). Despite initial hope and enthusiasm for the Milwaukee protocol for the treatment of rabies, subsequent trials of the protocol have failed.

[0012] In a recent animal study, Yamada and co-authors investigated the efficacy of favipiravir (T-507) against RABV (Yamada K, Noguchi K, Komeno T, Furuta Y, Nishizono A. 2016. Efficacy of favipiravir (T-705) in Rabies Postexposure Prophylaxis. J Infect Dis 213:1253–1261). Favipiravir is predicted to act as a chain terminator or mutagen on the viral RNA-dependent RNA polymerase. In this study, favipiravir was shown to be a potential alternative to rabies immunoglobulin in rabies PEP, but this antiviral agent showed little to no effect on RABV infection when given starting 1 or 2 days after viral inoculation, even at a high dose of 300 mg / kg / day.

[0013] WO 2016 / 078761 and De Benedicts et al. (De Benedictis P, Minola A, Rota Nodari E, Aiello R, Zecchin B, Salomoni A, Foglierini M, Agatic G, Vanzetta F, Lavenir R, Lepelletier A, Bentley E, Weiss R, Cattoli G, Capua I, Sallusto F, Wright E, Lanzavecchia A, Bourhy H, Corti D. 2016. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol Med 8:407–421) reported the selection of two highly potent human monoclonal antibodies (RVC58 and RVC20) that were able to broadly neutralize multiple lyssaviruses within a narrow and similar antibody concentration range compared to other monoclonal antibodies described in the literature (such as CR57, CR4098 and RAB1).

[0014] Since there is currently no therapy for lyssavirus infection, even if the patient has been exposed to the virus for more than 5 days before the first treatment, there is a need for effective treatment of lyssavirus infection. Developing such treatment would be particularly beneficial for at least two categories of patients: patients with known lyssavirus exposure but who have failed to undergo post-exposure prophylaxis in time due to environmental reasons and who are at increased risk of developing lyssavirus infection, and patients who are not aware of contact with the virus and / or who exhibit signs of disease (of varying severity) (e.g., individuals infected through unobtrusive contact with infected bats; e.g., in places where dog rabies is controlled, RABV from bat sources has become the cause of human rabies). In these individuals, lyssavirus may have reached CNS tissues, and early or late signs of the disease may also have occurred.

[0015] In view of the above, the object of the present invention is to provide a new treatment for lyssavirus infection, even if the subject has shown symptoms or has been exposed to the virus for more than 5 days before the first administration. In addition, another object of the present invention is to expand the post-exposure treatment window for lyssavirus infection, which is currently limited to the first day after infection. In addition, the object of the present invention is to provide an effective antibody that widely neutralizes multiple lyssaviruses at low doses, so as to treat and / or treat lyssavirus infection in post-exposure prophylaxis even if the initial administration is more than five days after the virus exposure.

[0016] This object is achieved by the subject matter listed below and in the dependent claims.

[0017] Project of the present invention

[0018] The present invention specifically provides the following items:

[0019] 1. An anti-rabies virus antibody or an antigen-binding fragment thereof for use in treating rabies virus infection, wherein the antibody or antigen-binding fragment thereof

[0020] (i) administered into the central nervous system (CNS); and

[0021] (ii) is given peripherally.

[0022] 2. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 1, wherein the antibody or antigen-binding fragment thereof is first administered at least five days after exposure to rabies virus.

[0023] 3. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 1, wherein the antibody or antigen-binding fragment thereof is first administered at least six days after exposure to rabies virus.

[0024] 4. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 1, wherein the antibody or antigen-binding fragment thereof is first administered at least seven days after exposure to rabies virus.

[0025] 5. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 1, wherein the antibody or antigen-binding fragment thereof is first administered at least eight days after exposure to rabies virus.

[0026] 6. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 5, wherein the antibody or antigen-binding fragment thereof is first administered after the onset of symptoms of rabies virus infection.

[0027] 7. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 6, wherein the peripheral administration of the antibody or antigen-binding fragment thereof and the administration of the antibody or antigen-binding fragment thereof into the CNS are performed at approximately the same time (simultaneously).

[0028] 8. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 6, wherein peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS are performed sequentially.

[0029] 9. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 8, wherein the time between peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS does not exceed one week.

[0030] 10. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 9, wherein the time between peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS does not exceed 3 days.

[0031] 11. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 10, wherein the time between peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS does not exceed 2 days.

[0032] 12. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 11, wherein the time between peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS does not exceed 24 hours.

[0033] 13. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 12, wherein the antibody or antigen-binding fragment thereof is administered peripherally while the antibody or antigen-binding fragment thereof is administered into the CNS.

[0034] 14. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-13, wherein the first peripheral administration of the antibody or antigen-binding fragment thereof and the first administration of the antibody or antigen-binding fragment thereof into the CNS occur on the same day.

[0035] 15. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 14, comprising a single peripheral administration of the antibody or antigen-binding fragment thereof.

[0036] 16. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 14, wherein the antibody or antigen-binding fragment thereof is repeatedly administered peripherally.

[0037] 17. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously into the CNS for at least 15 min.

[0038] 18. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously into the CNS for at least 30 min.

[0039] 19. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously into the CNS for at least 1 hour.

[0040] 20. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously into the CNS for at least 6 hours.

[0041] 21. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously into the CNS for at least 12 hours.

[0042] 22. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 24 hours.

[0043] 23. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 2 days.

[0044] 24. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 3 days.

[0045] 25. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 4 days.

[0046] 26. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 16, wherein the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 5 days.

[0047] 27. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-26, wherein the antibody or antigen-binding fragment thereof is administered into the CNS every day or every two days for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 days.

[0048] 28. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 27, wherein the antibody or antigen-binding fragment thereof administered into the CNS is administered into brain tissue.

[0049] 29. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 27, wherein the antibody or antigen-binding fragment thereof administered into the CNS is administered into spinal cord tissue.

[0050] 30. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 27, wherein the antibody or antigen-binding fragment thereof administered into the CNS is administered into the cerebrospinal fluid (intra-CSF).

[0051] 31. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 27, wherein administration into the CNS is selected from intrathecal administration, intracerebroventricular administration, intracerebral administration, epidural administration, transnasal administration, intranasal administration, and perimedullary administration.

[0052] 32. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered intrathecally.

[0053] 33. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered intracerebroventricularly.

[0054] 34. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered intracerebrally.

[0055] 35. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered epidurally.

[0056] 36. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered nasally.

[0057] 37. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered intranasally.

[0058] 38. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 31, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered perimedullatively.

[0059] 39. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 27, wherein the antibody or antigen-binding fragment thereof administered to the CNS is administered ocularly.

[0060] 40. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 39, wherein the antibody or antigen-binding fragment thereof is administered into the CNS by injection.

[0061] 41. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 40, wherein the antibody or antigen-binding fragment thereof is administered into the CNS by infusion.

[0062] 42. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 39, wherein the antibody or antigen-binding fragment thereof is administered into the CNS via a nasal device.

[0063] 43. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 42, wherein the antibody or antigen-binding fragment thereof is administered into the CNS by nebulization.

[0064] 44. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 42, wherein the antibody or antigen-binding fragment thereof is administered into the CNS via nasal drops.

[0065] 45. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 42, wherein the antibody or antigen-binding fragment thereof is administered into the CNS via a needle-free injector.

[0066] 46. ​​An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 42, wherein the antibody or antigen-binding fragment thereof is administered to the CNS via a nasal device designed to deposit nasally administered formulations specifically into the olfactory region.

[0067] 47. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 46, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered systemically.

[0068] 48. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 46, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered locally.

[0069] 49. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 46, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered enterally.

[0070] 50. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 46, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered parenterally.

[0071] 51. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 49, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered orally.

[0072] 52. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 49, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered rectally.

[0073] 53. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intravenously.

[0074] 54. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intramuscularly.

[0075] 55. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered subcutaneously.

[0076] 56. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intradermally.

[0077] 57. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intra-arterially.

[0078] 58. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered transdermally.

[0079] 59. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 50, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intraperitoneally.

[0080] 60. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 59, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered at the site of injury.

[0081] 61. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 60, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered in the same muscle or in the corresponding skin where the bite occurred.

[0082] 62. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 48, 60 and 61, wherein the peripherally administered antibody or antigen-binding fragment thereof is administered intramuscularly, intravenously, intradermally, or subcutaneously.

[0083] 63. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 62, wherein the same antibody or antigen-binding fragment thereof is administered peripherally and is administered into the CNS.

[0084] 64. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 62, wherein different antibodies or antigen-binding fragments thereof are administered peripherally and administered into the CNS.

[0085] 65. An anti-lyssavirus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 64, wherein the lyssavirus infection to be treated is rabies, and the anti-lyssavirus antibody or antigen-binding fragment thereof is an anti-RABV antibody or antigen-binding fragment thereof.

[0086] 66. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 65, wherein the antibody or antigen-binding fragment thereof binds to lyssavirus glycoprotein G.

[0087] 67. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 66, wherein the antibody or antigen-binding fragment thereof binds to glycoprotein G of RABV.

[0088] 68. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 67, wherein the antibody or antigen-binding fragment thereof binds to antigenic site I or antigenic site III of glycoprotein G of RABV.

[0089] 69. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 68, wherein the antibody or antigen-binding fragment thereof binds to antigenic site I of glycoprotein G of RABV.

[0090] 70. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 68, wherein the antibody or antigen-binding fragment thereof binds to antigenic site III of glycoprotein G of RABV.

[0091] 71. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 70, wherein the antibody or antigen-binding fragment thereof binds to an epitope that at least partially overlaps with antigenic site III of glycoprotein G of RABV.

[0092] 72. An anti-lyssavirus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 71, wherein the antibody or antigen-binding fragment thereof is administered in combination with other anti-lyssavirus antibodies or antigen-binding fragments thereof.

[0093] 73. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 72, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof to be administered in combination are administered in the same pharmaceutical composition.

[0094] 74. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 72, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof to be administered in combination are administered in different pharmaceutical compositions.

[0095] 75. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 72-74, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination into the CNS and the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination peripherally are the same antibody or antigen-binding fragment thereof.

[0096] 76. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 72-74, wherein the combination of two anti-rabies virus antibodies or antigen-binding fragments thereof administered into the CNS is different from the combination of two anti-rabies virus antibodies or antigen-binding fragments thereof administered peripherally.

[0097] 77. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 76, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered into the CNS are different from the two anti-rabies virus antibodies or antigen-binding fragments thereof administered peripherally.

[0098] 78. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 72 to 77, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination specifically bind to different epitopes on glycoprotein G of RABV.

[0099] 79. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 78, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof binds to antigenic site I of glycoprotein G of RABV, and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof binds to antigenic site III of glycoprotein G of RABV.

[0100] 80. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 72 to 79, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination are administered in equimolar amounts.

[0101] 81. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 80, wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody and / or a human antibody.

[0102] 82. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 81, wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody.

[0103] 83. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 81, wherein the antibody or antigen-binding fragment thereof is a human antibody.

[0104] 84. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 82, wherein the antibody or antigen-binding fragment thereof is a humanized antibody.

[0105] 85. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 82, wherein the antibody or antigen-binding fragment thereof is a chimeric antibody.

[0106] 86. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 85, wherein the antibody or antigen-binding fragment thereof is a recombinant antibody.

[0107] 87. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 86, wherein the antibody or antigen-binding fragment thereof is a genetically engineered antibody.

[0108] 88. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 87, wherein the antibody or antigen-binding fragment thereof is a purified antibody.

[0109] 89. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is a single-chain antibody.

[0110] 90. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is a Fab.

[0111] 91. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is a Fab'.

[0112] 92. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is F(ab')2.

[0113] 93. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is an Fv.

[0114] 94. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is a scFv.

[0115] 95. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is an IgG antibody.

[0116] 96. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is an IgM antibody.

[0117] 97. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 1 to 88, wherein the antibody or antigen-binding fragment thereof is an IgA antibody.

[0118] 98. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 95, wherein the antibody or antigen-binding fragment thereof is an IgG1 antibody.

[0119] 99. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 95, wherein the antibody or antigen-binding fragment thereof is an IgG2 antibody.

[0120] 100. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 95, wherein the antibody or antigen-binding fragment thereof is an IgG3 antibody.

[0121] 101. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 95, wherein the antibody or antigen-binding fragment thereof is an IgG4 antibody.

[0122] 102. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 101, wherein the antibody or antigen-binding fragment thereof has an IC value of less than 10,000 ng / ml. 50 Neutralizes lyssavirus infection of (i) RABV and (ii) at least 50% of a non-RABV lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, ARAV, LBV, MOK, SHIV, BBLV, WCBV, and IKOV.

[0123] 103. The antibody or antigen-binding fragment thereof according to item 102, characterized in that the antibody or antigen-binding fragment neutralizes lyssavirus infection of (i) RABV and (ii) at least 50% of all isolates of non-RABV lyssavirus, wherein the non-RABV lyssavirus is selected from ABLV / Australia / Bat / 9810AUS-1998 / V1039-2011 / ABLV, 98010 / ABLV, 1301 Boklo Bat Lyssavirus / BBLV, 86132SA / DUVV, DUVV / South Africa / Human / 96132SA-1971 / RS639-2012 / DUVV, EBLV1 a / France / bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV1b / France / bat / 8918-1989 / EBLV-1, EBLV2 / UK / bat / RV1332-2002 / V3951-2009 / EBLV-2, 94112 / EBLV-2, 02053 / EBLV-2, 8619 / LBV, MOK / MOK, Shimoni bat virus / SHIV, West Caucasian bat virus / WCBV, Australian bat lyssavirus / RV634 / ABLV, Aravanvirus / ARAV, Duvenhage virus RSA2006 / DUVV, Duvenhage virus ZIM86-RV 131 / DUVV, European bat lyssavirus 1.RV20 / EBLV-1, European bat lyssavirus 1.RV9 / EBLV-1, EBLV1a / France / Bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV2 / UK / Bat / RV1332-2002 / V3951-2009 / EBLV-2, European bat lyssavirus 2.RV1787 / EBLV-2, European bat lyssavirus 2.RV628 / EBLV-2, Irkut virus / IRKV, Kujand virus / KHUV, 8619 / LBV, Lagos bat virus NIG56-RV1 / LBV, Lagos bat virus SA2004 / LBV, Mokola virus NIG68.RV4 / MOK, Mokola virus 98 / 071RA36 / MOK, and Ikoma lyssavirus / IKOV, for ABLV / Australia / Bat / 9810AUS-1998 / V1039-2011 / ABLV, 98010 / ABLV, 1301 Boklo Bat Lyssavirus / BBLV, 86132SA / DUVV, DUVV / South Africa / Human / 96132SA-1971 / RS639 tested as infectious viruses -2012 / DUVV, EBLV1a / France / Bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV1b / France / Bat / 8918-1989 / EBLV-1, EBLV2 / UK / Bat / RV1332-2002 / V3951-2009 / EBLV-2, 94112 / EBLV-2, 02053 / EBLV-2, 8619 / LBV, MOK / MOK, IC. 50 Below 10,000 ng / ml and for the Shimoni Bat Virus / SHIV, West Caucasian Bat Virus / WCBV, Australian Bat Lyssavirus / RV634 / ABLV, Aravanvirus / ARAV, Duvenhei Virus RSA2006 / DUVV, Duvenhei Virus ZIM86-RV 131 / DUVV, European Bat Lyssavirus 1.RV20 / EBLV-1, European Bat Lyssavirus 1.RV9 / EBLV-1, EBLV1a / France / Bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV2 / UK / Bat / RV1332-2002 / V3951-2009 / EBLV-2, European Bat Lyssavirus 2.RV1787 tested as pseudotyped viruses. / EBLV-2, European bat lyssavirus 2.RV628 / EBLV-2, Irkut virus / IRKV, Kujand virus / KHUV, 8619 / LBV, Lagos bat virus NIG56-RV1 / LBV, Lagos bat virus SA2004 / LBV, Mokola virus NIG68.RV4 / MOK, Mokola virus 98 / 071RA36 / MOK and Ikoma lyssavirus / IKOV, IC 90 Below 10000ng / ml.

[0124] 104. The antibody or antigen-binding fragment thereof according to item 102 or 103, characterized in that the antibody or antigen-binding fragment has an IC value of less than 10000 ng / ml. 50Neutralizes at least 70% of lyssavirus infection by a non-RABV genetic lineage I lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, ARAV, and BBLV.

[0125] 105. The antibody or antigen-binding fragment thereof according to item 102 or 103, characterized in that the antibody or antigen-binding fragment has an IC value of less than 10000 ng / ml. 50 Neutralizes at least 70% of lyssavirus infection by a non-RABV genetic lineage I lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, and ARAV.

[0126] 106. The antibody or antigen-binding fragment thereof according to item 105, characterized in that the antibody or antigen-binding fragment has an IC value of less than 10000 ng / ml. 50 Neutralizes at least 75% of lyssavirus infection by a non-RABV genetic lineage I lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, and ARAV.

[0127] 107. The antibody or antigen-binding fragment thereof according to item 106, characterized in that the antibody or antigen-binding fragment has an IC value of less than 10000 ng / ml. 50 Neutralizes at least 80% of lyssavirus infection by a non-RABV genetic lineage I lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, and ARAV.

[0128] 108. The antibody or antigen-binding fragment thereof according to item 107, characterized in that the antibody or antigen-binding fragment has an IC value of less than 10000 ng / ml. 50 Neutralizes at least 82% of lyssavirus infection by a non-RABV genetic lineage I lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, and ARAV.

[0129] 109. The antibody or antigen-binding fragment thereof according to any one of items 1-108, characterized in that the antibody or antigen-binding fragment neutralizes at least 70% of lyssavirus infection of an isolate of a non-RABV genetic lineage I lyssavirus, wherein the non-RABV genetic lineage I lyssavirus is selected from ABLV / Australia / Bat / 9810AUS-1998 / V1039-2011 / ABLV, 98010 / ABLV, 1301 Boklo Bat Lyssavirus / BBLV, 86132SA / DUVV, DUVV / South Africa / Human / 96132SA-1971 / RS6 39-2012 / DUVV, EBLV1a / France / Bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV1b / France / Bat / 8918-1989 / EBLV-1, EBLV2 / UK / Bat / RV1332-2002 / V3951-2009 / EBLV-2, 94112 / EBLV-2, 02053 / EBLV-2, Australian Bat Lyssavirus / RV634 / ABLV, Aravanvirus / ARAV, Duvenhage virus RSA2006 / DUVV, Duvenhage virus ZIM86-RV 131 / DUVV, European bat lyssavirus 1.RV20 / EBLV-1, European bat lyssavirus 1.RV9 / EBLV-1, EBLV1a / France / bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV2 / UK / bat / RV1332-2002 / V3951-2009 / EBLV-2, European bat lyssavirus 2.RV1787 / EBLV-2 and European bat lyssavirus 2.RV628 / EBLV- 2. Irkut virus / IRKV, Kujand virus / KHUV, for ABLV / Australia / Bat / 9810AUS-1998 / V1039-2011 / ABLV, 98010 / ABLV, 1301 Boklo Bat Lyssavirus / BBLV, 86132SA / DUVV, DUVV / South Africa / Human / 96132SA-1971 / RS639-2012 / DUVV, EBLV1a / France / Bat / 122938-2002 / V3951 tested as infectious viruses -2009 / EBLV-1, EBLV1b / France / Bat / 8918-1989 / EBLV-1, EBLV2 / UK / Bat / RV1332-2002 / V3951-2009 / EBLV-2, 94112 / EBLV-2 and 02053 / EBLV-2, IC 50Below 10,000 ng / ml, and for the pseudotyped viruses tested, Australian bat lyssavirus / RV634 / ABLV, Aravanvirus / ARAV, Duvenheivirus RSA2006 / DUVV, Duvenheivirus ZIM86-RV 131 / DUVV, European bat lyssavirus 1.RV20 / EBLV-1, European bat lyssavirus 1.RV9 / EBLV-1, EBLV1a / France / bat / 122938-2002 / V3951-2009 / EBLV-1, EBLV2 / UK / bat / RV1332-2002 / V3951-2009 / EBLV-2, European bat lyssavirus 2.RV1787 / EBLV-2, European bat lyssavirus 2.RV628 / EBLV-2, Irkut virus / IRKV, and Kujand virus / KHUV, IC 90 Below 10000ng / ml.

[0130] 110. The antibody or antigen-binding fragment thereof according to any one of items 1 to 109, characterized in that the antibody or antigen-binding fragment neutralizes EBLV-1 infection.

[0131] 111. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 110, wherein the antibody or antigen-binding fragment thereof has an IC of 400 ng / ml or less. 90 Neutralizes RABV CVS-11 infection.

[0132] 112. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-111, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 70% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 70% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 173-174. and SEQ ID NOs: 165-168 and 170-171; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7, respectively, or to the amino acid sequences of SEQ ID NOs: 1-4 and 6-7; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 19-23 and 25, respectively, or to the amino acid sequences of SEQ ID NOs: 19-22 and 24-25; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 37-41 and 43, respectively, or to the amino acid sequences of SEQ ID NOs: (vi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 55-59 and 61, respectively, or to the amino acid sequences of SEQ ID NOs: 55-58 and 60-61; (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81, respectively, or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0133] 113. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 112, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 75% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 75% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 75% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 75% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 75% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0134] 114. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 113, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 173-174. NOs: 165-168 and 170-171; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7, or to the amino acid sequences of SEQ ID NOs: 1-4 and 6-7, respectively; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 19-23 and 25, respectively, or to the amino acid sequences of SEQ ID NOs: 19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 55-58 and 60-61, respectively; (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81, or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117, respectively; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135, respectively; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0135] 115. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 114, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 80% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 80% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 80% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 80% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0136] 116. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 115, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 85% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 85% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 85% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 85% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 85% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 85% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 85% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0137] 117. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 116, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 88% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 88% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 88% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 88% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 88% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0138] 118. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 117, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 90% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 90% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 90% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 90% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0139] 119. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 118, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 92% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 92% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 92% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 92% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 92% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 92% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 92% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0140] 120. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 119, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 95% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 95% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 95% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 95% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0141] 121. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 120, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 97% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 97% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 97% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 97% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or to an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or to an amino acid sequence of SEQ ID NOs: 37-40 and 42-43, respectively; (vi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0142] 122. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 121, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 98% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 98% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 98% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence that is at least 98% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 98% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 98% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that is at least 98% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0143] 123. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 122, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 99% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 99% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 99% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7 or an amino acid sequence at least 99% identical to an amino acid sequence of SEQ ID NOs: 1-4 and 6-7; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 99% identical to an amino acid sequence of SEQ ID NOs: 19-23 and 25, or an amino acid sequence of SEQ ID NOs: 19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 99% identical to an amino acid sequence of SEQ ID NOs: 37-41 and 43, respectively, or an amino acid sequence of SEQ ID NOs: 37-40 and 42-43; (vi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences at least 99% identical to an amino acid sequence of SEQ ID NOs: (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81 or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, respectively, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, respectively, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0144] 124. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 123, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NOs: 93-97 and 99 or in SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NOs: 165-169 and 171 or in SEQ ID NOs: 165-168 and 170-171, respectively; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NOs: 1-5 and 7 or in SEQ ID NOs: NO:1-4 and 6-7; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NO:19-23 and 25 or in SEQ ID NO:19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NO:37-41 and 43 or in SEQ ID NO:37-40 and 42-43, respectively; (vi) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are set forth in SEQ ID NO:55-59 and 61, respectively or in SEQ ID (vii) the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 75-79 and 81 or in SEQ ID NOs: 75-78 and 80-81, respectively; (viii) the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 111-115 and 117 or in SEQ ID NOs: 111-114 and 116-117, respectively;(ix) the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 129-133 and 135 or in SEQ ID NOs: 129-132 and 134-135, respectively; (x) the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 147-151 and 153 or in SEQ ID NOs: 147-150 and 152-153, respectively; (xi) the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 183-187 and 189 or in SEQ ID NOs: or (xii) the heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2, and CDRL3 amino acid sequences set forth in SEQ ID NOs: 201-205 and 207 or in SEQ ID NOs: 201-204 and 206-207, respectively.

[0145] 125. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 112, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 70% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0146] 126. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 125, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0147] 127. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 126, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0148] 128. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 127, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0149] 129. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 128, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 85% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0150] 130. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 129, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0151] 131. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 130, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0152] 132. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 131, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 92% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0153] 133. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 132, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 95% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0154] 134. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 133, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 97% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0155] 135. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 134, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 98% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0156] 136. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 135, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 99% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0157] 137. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 135, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are listed in SEQ ID NOs: 93-97 and 99 or in SEQ ID NOs: 93-96 and 98-99, respectively.

[0158] 138. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 112, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 70% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0159] 139. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 138, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0160] 140. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 139, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0161] 141. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 141, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0162] 142. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 141, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 85% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0163] 143. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 142, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0164] 144. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 143, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0165] 145. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 144, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 92% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0166] 146. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 145, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 95% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0167] 147. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 146, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 97% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0168] 148. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 147, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 98% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0169] 149. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 148, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 99% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0170] 150. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 112, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are listed in SEQ ID NOs: 165-169 and 171 or in SEQ ID NOs: 165-168 and 170-171, respectively.

[0171] 151. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 124, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 34. NO:34; or (v) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:51 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: NO: 125 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 126; or (x) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0172] 152. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 152, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0173] 153. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 152, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180. NO:33 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:34; or (v) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:51 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:51 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:52 NO:89 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:126; or (x) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:143 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:144;or (xi) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 162; or (xii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0174] 154. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 153, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0175] 155. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 154, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0176] 156. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 155, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0177] 157. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 156, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0178] 158. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 157, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0179] 159. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 158, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 35 NO:51 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0180] 160. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 159, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 180. NO:51 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region 2 that has at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 16;or (xii) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0181] 161. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 160, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 180. NO:51 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region 2 that has at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 16;or (xii) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0182] 162. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 161, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 33 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; or (v) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 180. NO:51 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:89 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: NO: 126; or (x) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 143 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 144; or (xi) a heavy chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 162;or (xii) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0183] 163. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 162, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region set forth in SEQ ID NO: 107 and a light chain variable region set forth in SEQ ID NO: 108; or (ii) a heavy chain variable region set forth in SEQ ID NO: 179 and a light chain variable region set forth in SEQ ID NO: 180; or (iii) a heavy chain variable region set forth in SEQ ID NO: 15 and a light chain variable region set forth in SEQ ID NO: 16; or (iv) a heavy chain variable region set forth in SEQ ID NO: 33 and a light chain variable region set forth in SEQ ID NO: 34; or (v) a heavy chain variable region set forth in SEQ ID NO: 51 and a light chain variable region set forth in SEQ ID NO: 52; or (vi) a heavy chain variable region set forth in SEQ ID NO: 69 and a light chain variable region set forth in SEQ ID NO: 71; or (vii) a heavy chain variable region set forth in SEQ ID NO: 80 or (x) the heavy chain variable region set forth in SEQ ID NO: 143 and the light chain variable region set forth in SEQ ID NO: 144; or (xi) the heavy chain variable region set forth in SEQ ID NO: 161 and the light chain variable region set forth in SEQ ID NO: 162; or (xii) the heavy chain variable region set forth in SEQ ID NO: 197 and the light chain variable region set forth in SEQ ID NO: 198; or (xiii) the heavy chain variable region set forth in SEQ ID NO: 215 and the light chain variable region set forth in SEQ ID NO: 216.

[0184] 164. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 151, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0185] 165. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 164, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 75% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 75% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0186] 166. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 165, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0187] 167. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 166, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0188] 168. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 167, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 85% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0189] 169. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 168, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 88% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 88% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0190] 170. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 169, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0191] 171. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 170, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 92% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 92% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0192] 172. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 171, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0193] 173. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 172, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 97% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 97% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0194] 174. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 173, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0195] 175. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 174, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0196] 176. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 175, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain variable region listed in SEQ ID NO: 107 and the light chain variable region listed in SEQ ID NO: 108.

[0197] 177. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 151, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0198] 178. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 177, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 75% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 75% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0199] 179. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 178, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0200] 180. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 179, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0201] 181. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 180, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 85% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 85% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0202] 182. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 181, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 88% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 88% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0203] 183. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 182, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0204] 184. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 183, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 92% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 92% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0205] 185. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 184, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0206] 186. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 185, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 97% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 97% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0207] 187. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 186, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0208] 188. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 187, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 99% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0209] 189. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 188, wherein the antibody or antigen-binding fragment thereof comprises the heavy chain variable region listed in SEQ ID NO: 179 and the light chain variable region listed in SEQ ID NO: 180.

[0210] 190. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-190, wherein the antibody or antigen-binding fragment thereof is RVC20, RVC58, RVA122, RVA144, RVB185, RVB492, RVC3, RVC21, RVC38, RVC44, RVC68, or RVC111.

[0211] 191. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-190, wherein the antibody or antigen-binding fragment thereof is RVC20 or RVC58.

[0212] 192. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 191, wherein the antibody or antigen-binding fragment thereof is RVC20.

[0213] 193. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1-191, wherein the antibody or antigen-binding fragment thereof is RVC58.

[0214] 194. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to items 72-80, wherein at least one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination is as defined in any one of items 112-193.

[0215] 195. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to items 72-80, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination are as defined in any one of items 112-193.

[0216] 196. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 72–80 and 194–195, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 70% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171.

[0217] 197. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 196, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 75% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0218] 198. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 197, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0219] 199. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 198, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0220] 200. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 199, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 85% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0221] 201. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 200, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 88% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0222] 202. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 201, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0223] 203. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 202, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 92% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171.

[0224] 204. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 203, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 95% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0225] 205. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 204, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 97% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0226] 206. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 205, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 98% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171.

[0227] 207. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 206, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 99% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0228] 208. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 207, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 93-97 and 99, or in the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises the heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and the light chain CDRL1, CDRL2 and CDRL3 amino acid sequences set forth in SEQ ID NOs: 165-169 and 171, or in the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0229] 209. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 196, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 70% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0230] 210. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 209, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 75% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0231] 211. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 210, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0232] 212. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 211, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0233] 213. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 212, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 85% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0234] 214. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 213, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0235] 215. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 214, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0236] 216. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 215, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 92% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0237] 217. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 216, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0238] 218. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 217, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 97% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0239] 219. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to item 218, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0240] 220. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 219, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0241] 221. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 220, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises the heavy chain variable region set forth in SEQ ID NO: 107 and the light chain variable region set forth in SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises the heavy chain variable region set forth in SEQ ID NO: 179 and the light chain variable region set forth in SEQ ID NO: 180.

[0242] 222. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 112-123, 125-136, 138-149, 151-162, 164-175, 177-188, 196-207, and 209-220, wherein the amino acid sequence comprises a deletion of one or more amino acids compared to the reference sequence.

[0243] 223. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 112–123, 125–136, 138–149, 151–162, 164–175, 177–188, 196–207, 209–220, and 222, wherein the amino acid sequence comprises an insertion of one or more amino acids compared to the reference sequence.

[0244] 224. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 112–123, 125–136, 138–149, 151–162, 164–175, 177–188, 196–207, 209–220, 222, and 223, wherein the amino acid sequence comprises one or more amino acid substitutions compared to a reference sequence.

[0245] 225. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 224, wherein the substitution is a conservative substitution.

[0246] 226. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 224 or 225, wherein the substitution is not a conservative substitution.

[0247] 227. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 112–123, 125–136, 138–149, 151–162, 164–175, 177–188, 196–207, 209–220, and 222–226, wherein the change(s) in the amino acid sequence compared to the reference sequence do not abolish functionality.

[0248] 228. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 227, wherein the functionality is binding to the same epitope as the reference sequence.

[0249] 229. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 227 or 228, wherein the functionality is neutralization of rabies virus infection.

[0250] 230. An anti-lyssavirus antibody or antigen-binding fragment thereof for use according to item 229, wherein the lyssavirus is RABV.

[0251] 231. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 229, wherein the rabies virus is EBLV-1.

[0252] 232. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 1 to 231, wherein the antibody or antigen-binding fragment thereof is contained in a pharmaceutical composition.

[0253] 233. A nucleic acid molecule comprising a polynucleotide encoding an anti-rabies virus antibody or an antigen-binding fragment thereof for use in treating rabies virus infection, wherein the nucleic acid molecule

[0254] (i) administered into the central nervous system (CNS); and

[0255] (ii) is given peripherally.

[0256] 234. The nucleic acid molecule for use according to item 233, wherein the nucleic acid molecule is administered as defined in any one of items 2-80.

[0257] 235. The nucleic acid molecule for use according to item 233 or 234, wherein the encoded anti-rabies virus antibody or antigen-binding fragment thereof is as defined in any one of items 81-231.

[0258] 236. A nucleic acid molecule for use according to any one of items 233-235, wherein the nucleic acid is DNA.

[0259] 237. A nucleic acid molecule for use according to any one of items 233-235, wherein the nucleic acid is RNA.

[0260] 238. A combination of at least two different nucleic acid molecules encoding anti-rabies virus antibodies or antigen-binding fragments thereof, wherein one nucleic acid molecule encodes at least CDRH1, CDRH2 and CDRH3 of the heavy chain of the anti-rabies virus antibody, and the other nucleic acid molecule encodes at least CDRL1, CDRL2 and CDRL3 of the corresponding light chain of the anti-rabies virus antibody, for use in treating rabies virus infection, wherein the nucleic acid molecules

[0261] (i) administered into the central nervous system (CNS); and

[0262] (ii) is given peripherally.

[0263] 239. The combination for use according to item 238, wherein one nucleic acid molecule encodes at least the variable region of the heavy chain (VH) of the anti-rabies virus antibody, and the other nucleic acid molecule encodes at least the corresponding variable region of the light chain (VL) of the anti-rabies virus antibody.

[0264] 240. The combination for use according to item 238, wherein one nucleic acid molecule encodes the heavy chain of the anti-lyssavirus antibody and the other nucleic acid molecule encodes the corresponding light chain of the anti-lyssavirus antibody.

[0265] 241. The combination for use according to any one of items 238-240, wherein the encoded anti-rabies virus antibody or antigen-binding fragment thereof is as defined in any one of items 80-231.

[0266] 242. Combination for use according to any of items 238-241, wherein the combination is administered as defined in any of items 2-80.

[0267] 243. The combination for use according to any one of items 238-242, wherein the nucleic acid is DNA.

[0268] 244. The combination for use according to any one of items 238-242, wherein the nucleic acid is RNA.

[0269] 245. A pharmaceutical composition comprising (as an active ingredient) an anti-rabies virus antibody or an antigen-binding fragment thereof for use in treating rabies virus infection, wherein the pharmaceutical composition

[0270] (i) administered into the central nervous system (CNS); and

[0271] (ii) is given peripherally.

[0272] 246. A pharmaceutical composition for the use according to item 245, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier, diluent or excipient.

[0273] 247. A pharmaceutical composition for the use according to item 246, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.

[0274] 248. A pharmaceutical composition for use according to item 246 or 247, wherein the pharmaceutical composition comprises a pharmaceutically acceptable diluent.

[0275] 249. A pharmaceutical composition for use according to any one of items 246-248, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient.

[0276] 250. A pharmaceutical composition for use according to any one of items 246-249, wherein the pharmaceutical composition comprises saline.

[0277] 251. A pharmaceutical composition for use according to any one of items 246-249, wherein the pharmaceutical composition comprises a buffer.

[0278] 252. A pharmaceutical composition for use according to any one of items 246-249, wherein the pharmaceutical composition comprises phosphate buffered saline (PBS).

[0279] 253. A pharmaceutical composition for use according to any one of items 246-252, wherein the pH of the pharmaceutical composition is between 5.5 and 8.5.

[0280] 254. A pharmaceutical composition for use according to item 253, wherein the pH of the pharmaceutical composition is between 6 and 8.

[0281] 255. The pharmaceutical composition for use according to item 254, wherein the pH of the pharmaceutical composition is between 6.5 and 7.5.

[0282] 256. A pharmaceutical composition for use according to any one of items 245-255, wherein the pharmaceutical composition is administered as defined in any one of items 2-80.

[0283] 257. A pharmaceutical composition for use according to any one of items 245-256, wherein the anti-rabies virus antibody or antigen-binding fragment thereof is as defined in any one of items 81-231.

[0284] 258. A pharmaceutical composition for use according to any one of items 245-257, wherein the pharmaceutical composition comprises at least two different anti-rabies virus antibodies or antigen-binding fragments thereof as defined in any one of items 81-231.

[0285] 259. The pharmaceutical composition for use according to item 258, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to different epitopes on glycoprotein G of RABV.

[0286] 260. The pharmaceutical composition for use according to item 259, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to antigenic site I of glycoprotein G of RABV and bind to antigenic site III of glycoprotein G of RABV.

[0287] 261. A pharmaceutical composition for use according to any one of items 245-260, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0288] 262. A pharmaceutical composition for use according to item 261, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0289] 263. A pharmaceutical composition for use according to any one of items 245-262, wherein the at least two different anti-rabies virus antibodies or antigen-binding fragments thereof are contained in the pharmaceutical composition in equimolar amounts.

[0290] 264. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to any of items 1-232, a nucleic acid molecule for the use according to any of items 233-237, a combination for the use according to any of items 238-244, or a pharmaceutical composition for the use according to any of items 245-263, wherein the antibody or antigen-binding fragment thereof, the nucleic acid molecule, or the pharmaceutical composition is administered in combination with an anti-rabies virus vaccine, an antiviral agent, interferon-α and / or ketamine.

[0291] 265. An anti-rabies virus antibody or antigen-binding fragment thereof, or a pharmaceutical composition for the use according to item 264, wherein the anti-rabies virus vaccine is a rabies vaccine.

[0292] 266. An anti-rabies virus antibody or antigen-binding fragment thereof, or a pharmaceutical composition for use according to item 264 or 265, wherein the antiviral agent is ribavirin.

[0293] 267. An anti-rabies virus antibody or antigen-binding fragment thereof for the use according to any of items 1-232, a nucleic acid molecule for the use according to any of items 233-237, a combination for the use according to any of items 238-244, or a pharmaceutical composition for the use according to any of items 245-263, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered without concomitant administration of an anti-rabies virus vaccine and / or without subsequent administration of an anti-rabies virus vaccine.

[0294] 268. A kit of parts comprising at least one antibody or antigen-binding fragment thereof as defined in any one of items 65 to 232, at least one nucleic acid molecule as defined in any one of items 233–237, a combination as defined in any one of items 238–244, or at least one pharmaceutical composition according to any one of items 245 to 263, for use in treating lyssavirus infection, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered as defined in any one of items 1–62.

[0295] 269. A kit of parts for use according to item 268, wherein the kit of parts comprises at least two different anti-lyssavirus antibodies or antigen-binding fragments thereof as defined in any one of items 65-232.

[0296] 270. The kit of parts for use according to item 269, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to different epitopes on glycoprotein G of RABV.

[0297] 271. The kit of parts for use according to item 270, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to antigenic site I of glycoprotein G of RABV and bind to antigenic site III of glycoprotein G of RABV.

[0298] 272. A kit of parts for use according to any one of items 269-271, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0299] 273. A kit of parts for use according to item 272, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0300] 274. A method for treating or attenuating a lyssavirus infection in a subject, wherein the method comprises administering to a subject in need thereof an antibody or antigen-binding fragment thereof as defined in any one of items 1-232, at least one nucleic acid molecule as defined in any one of items 233-237, a combination as defined in any one of items 238-244, or a pharmaceutical composition according to any one of items 245-263, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition

[0301] (i) administered into the central nervous system (CNS); and

[0302] (ii) is given peripherally.

[0303] 275. The method of claim 274, wherein the subject is a human subject.

[0304] 276. The method of claim 274, wherein the subject is an animal subject.

[0305] 277. The method of claim 276, wherein the subject is selected from the group consisting of cows, dogs, cats, horses, goats, sheep, pigs, and rabbits.

[0306] 278. An anti-rabies virus antibody or antigen-binding fragment thereof, comprising an Fc portion comprising a CH2 domain and a CH2 L4A mutation and / or a CH2 L5A mutation.

[0307] 279. An anti-rabies virus antibody or antigen-binding fragment thereof according to item 278, wherein the Fc portion further comprises a hinge domain.

[0308] 280. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 278 or 279, wherein the Fc portion further comprises a CH3 domain.

[0309] 281. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-280, which comprises an Fc region.

[0310] 282. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-281, wherein the Fc portion is monomeric.

[0311] 283. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-282, wherein the Fc portion is a dimer.

[0312] 284. An anti-rabies virus antibody or antigen-binding fragment thereof according to item 283, wherein the Fc portion is a homodimer.

[0313] 285. An anti-rabies virus antibody or antigen-binding fragment thereof according to item 283, wherein the Fc portion is a heterodimer.

[0314] 286. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-285, wherein the Fc portion comprises an amino acid sequence derived from a human immunoglobulin sequence.

[0315] 287. An anti-rabies virus antibody or antigen-binding fragment thereof according to item 286, wherein the Fc portion comprises a human immunoglobulin sequence.

[0316] 288. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-287, wherein the Fc portion is human.

[0317] 289. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-288, which comprises an Fc region derived from human IgG1.

[0318] 290. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-289, which comprises a human IgG1 Fc region.

[0319] 291. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-290, which comprises a CH1 region.

[0320] 292. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-291, which comprises IgGCH1-CH2-CH3.

[0321] 293. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 292, which comprises human IgG1CH1-CH2-CH3.

[0322] 294. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 70% identical to SEQ ID NO: 219.

[0323] 295. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 75% identical to SEQ ID NO: 219.

[0324] 296. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 80% identical to SEQ ID NO: 219.

[0325] 297. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 219.

[0326] 298. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 88% identical to SEQ ID NO: 219.

[0327] 299. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 219.

[0328] 300. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, comprising an amino acid sequence that is at least 92% identical to SEQ ID NO: 219.

[0329] 301. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 219.

[0330] 302. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-293, comprising an amino acid sequence that is at least 98% identical to SEQ ID NO: 219.

[0331] 303. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-293, which comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 219.

[0332] 304. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-293, comprising the amino acid sequence set forth in SEQ ID NO: 219.

[0333] 305. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 72-304, wherein the anti-lyssavirus antibody or antigen-binding fragment thereof is an anti-RABV antibody or antigen-binding fragment thereof.

[0334] 306. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278-305, wherein the antibody or antigen-binding fragment thereof binds to lyssavirus glycoprotein G.

[0335] 307. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 306, wherein the antibody or antigen-binding fragment thereof binds to glycoprotein G of RABV.

[0336] 308. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 307, wherein the antibody or antigen-binding fragment thereof binds to antigenic site I or antigenic site III of glycoprotein G of RABV.

[0337] 309. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-308, wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody and / or a human antibody.

[0338] 310. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-309, wherein the antibody or antigen-binding fragment thereof has an IC value of less than 10,000 ng / ml. 50 Neutralizes lyssavirus infection of (i) RABV and (ii) at least 50% of a non-RABV lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, ARAV, LBV, MOK, SHIV, BBLV, and WCBV.

[0339] 311. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-310, wherein the antibody or antigen-binding fragment thereof has an IC of 400 ng / ml or less. 90Neutralizes RABV CVS-11 infection.

[0340] 312. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-311, wherein the antibody or antigen-binding fragment thereof comprises: (i) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; (ii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, respectively, or to the amino acid sequences of SEQ ID NOs: 173-179 and 180, respectively. NOs: 165-168 and 170-171; (iii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 1-5 and 7, or to the amino acid sequences of SEQ ID NOs: 1-4 and 6-7, respectively; (iv) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 19-23 and 25, respectively, or to the amino acid sequences of SEQ ID NOs: 19-22 and 24-25, respectively; (v) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 57-58 and 60-61, respectively; (vii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 75-79 and 81, or to the amino acid sequences of SEQ ID NOs: 75-78 and 80-81, respectively;(viii) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 111-115 and 117, or to the amino acid sequences of SEQ ID NOs: 111-114 and 116-117, respectively; (ix) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 129-133 and 135, or to the amino acid sequences of SEQ ID NOs: 129-132 and 134-135, respectively; (x) heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 147-151 and 153, respectively, or to the amino acid sequences of SEQ ID NOs: (xi) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 183-187 and 189, or to the amino acid sequences of SEQ ID NOs: 183-186 and 188-189, respectively; or (xii) heavy chain CDRH1, CDRH2, and CDRH3 amino acid sequences and light chain CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 201-205 and 207, or to the amino acid sequences of SEQ ID NOs: 201-204 and 206-207, respectively.

[0341] 313. An anti-rabies virus antibody or antigen-binding fragment thereof according to items 278–312, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99 or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively.

[0342] 314. An anti-rabies virus antibody or antigen-binding fragment thereof according to items 278–312, wherein the antibody or antigen-binding fragment thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171 or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0343] 315. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-314, wherein the antibody or antigen-binding fragment thereof comprises: (i) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; or (ii) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180; or (iii) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 15 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 16; or (iv) a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180. NO:33 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:34; or (v) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:51 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:52; or (vi) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:69 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (vii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:70 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:71; or (viii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:51 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:52 NO:89 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:90; or (ix) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:125 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:126; or (x) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:143 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO:144;or (xi) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 161 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 162; or (xii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 197 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 198; or (xiii) a heavy chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 215 and a light chain variable region that has at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 216.

[0344] 316. An anti-rabies virus antibody or antigen-binding fragment thereof according to claim 315, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108.

[0345] 317. An anti-rabies virus antibody or antigen-binding fragment thereof according to items 278–316, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0346] 318. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278–317, wherein the antibody or antigen-binding fragment thereof is RVC20, RVC58, RVA122, RVA144, RVB185, RVB492, RVC3, RVC21, RVC38, RVC44, RVC68, or RVC111.

[0347] 319. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-318, wherein the antibody or antigen-binding fragment thereof is RVC20 or RVC58.

[0348] 320. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-319, wherein the antibody or antigen-binding fragment thereof is a purified antibody.

[0349] 321. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-320, wherein the antibody or antigen-binding fragment thereof is a single-chain antibody.

[0350] 322. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is a Fab.

[0351] 323. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is a Fab'.

[0352] 324. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is F(ab')2.

[0353] 325. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is an Fv.

[0354] 326. An anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is a scFv.

[0355] 327. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is an IgG antibody.

[0356] 328. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is an IgM antibody.

[0357] 329. The anti-rabies virus antibody or antigen-binding fragment thereof according to any one of items 278-321, wherein the antibody or antigen-binding fragment thereof is an IgA antibody.

[0358] 330. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 327, wherein the antibody or antigen-binding fragment thereof is an IgG1 antibody.

[0359] 331. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 327, wherein the antibody or antigen-binding fragment thereof is an IgG2 antibody.

[0360] 332. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 327, wherein the antibody or antigen-binding fragment thereof is an IgG3 antibody.

[0361] 333. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 327, wherein the antibody or antigen-binding fragment thereof is an IgG4 antibody.

[0362] 334. The anti-lyssavirus antibody or antigen-binding fragment thereof according to any one of items 278 to 333, for use in preventing and / or treating lyssavirus infection.

[0363] 335. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.005 to 100 mg / kg.

[0364] 336. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.0075 to 50 mg / kg.

[0365] 337. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.01 to 10 mg / kg.

[0366] 338. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.01 to 1 mg / kg.

[0367] 339. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.01 to 0.1 mg / kg.

[0368] 340. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.01 to 100 mg / kg.

[0369] 341. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 0.1 to 75 mg / kg.

[0370] 342. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 1 to 60 mg / kg.

[0371] 343. The anti-rabies virus antibody or antigen-binding fragment thereof according to item 334, wherein the antibody or antigen-binding fragment thereof is administered at a dose of 10 to 50 mg / kg.

[0372] 344. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 334-343, wherein the antibody or antigen-binding fragment thereof is administered in combination with other anti-rabies virus antibodies or antigen-binding fragments thereof.

[0373] 345. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 344, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination specifically bind to different epitopes on glycoprotein G of RABV.

[0374] 346. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 345, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof binds to antigenic site I of glycoprotein G of RABV, and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof binds to antigenic site III of glycoprotein G of RABV.

[0375] 347. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 344-346, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination comprises a heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequence and a light chain CDRL1, CDRL2 and CDRL3 amino acid sequence that are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0376] 348. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to item 347, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments administered in combination comprises a heavy chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 180.

[0377] 349. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 344 to 348, wherein the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination are administered in equimolar amounts.

[0378] 350. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of items 334-349, wherein the antibody or antigen-binding fragment thereof is administered as defined in items 1-232.

[0379] 351. A nucleic acid molecule comprising a polynucleotide encoding the antibody or antigen-binding fragment thereof according to any one of items 278-333.

[0380] 352. A nucleic acid molecule according to item 351, wherein the nucleic acid is DNA.

[0381] 353. A nucleic acid molecule according to item 351, wherein the nucleic acid is cDNA.

[0382] 354. A nucleic acid molecule according to item 351, wherein the nucleic acid is RNA.

[0383] 355. A nucleic acid molecule according to item 351, wherein the nucleic acid is mRNA.

[0384] 356. A nucleic acid molecule according to item 351, wherein the nucleic acid is rRNA.

[0385] 357. A nucleic acid molecule according to item 351, wherein the nucleic acid is miRNA.

[0386] 358. A nucleic acid molecule according to item 351, wherein the nucleic acid is siRNA.

[0387] 359. A nucleic acid molecule according to item 351, wherein the nucleic acid is tRNA.

[0388] 360. A nucleic acid molecule according to any one of items 351–359, wherein the polynucleotide sequence is at least 75% identical to the nucleic acid sequence of any one of SEQ ID NOs: 8-14, 17, 18, 26-32, 35, 36, 44-50, 53, 54, 62-68, 72-74, 82-88, 91, 92, 100-106, 109, 110, 118-124, 127, 128, 136-142, 145, 146, 154-160, 163, 164, 172-178, 181, 182, 190-196, 199, 200, 208-214, 217 and 218.

[0389] 361. A combination of at least two different nucleic acid molecules encoding an anti-rabies virus antibody or antigen-binding fragment thereof according to any of items 72-88, wherein one nucleic acid molecule encodes at least CDRH1, CDRH2 and CDRH3 of the heavy chain of the anti-rabies virus antibody or antigen-binding fragment, and the other nucleic acid molecule encodes at least CDRL1, CDRL2 and CDRL3 of the corresponding light chain of the anti-rabies virus antibody or antigen-binding fragment.

[0390] 362. The combination according to item 361, wherein one nucleic acid molecule encodes at least the variable region of the heavy chain (VH) of the anti-rabies virus antibody, and the other nucleic acid molecule encodes at least the corresponding variable region of the light chain (VL) of the anti-rabies virus antibody.

[0391] 363. The combination according to item 362, wherein one nucleic acid molecule encodes the heavy chain of the anti-lyssavirus antibody and the other nucleic acid molecule encodes the corresponding light chain of the anti-lyssavirus antibody.

[0392] 364. A combination according to any one of items 361-363, wherein the nucleic acid is DNA.

[0393] 365. A combination according to item 364, wherein the nucleic acid is cDNA.

[0394] 366. A combination according to any one of items 361-363, wherein the nucleic acid is RNA.

[0395] 367. The combination according to item 366, wherein the nucleic acid is mRNA.

[0396] 368. The combination according to item 366, wherein the nucleic acid is rRNA.

[0397] 369. The combination according to item 366, wherein the nucleic acid is miRNA.

[0398] 370. The combination according to item 366, wherein the nucleic acid is siRNA.

[0399] 371. The combination according to item 366, wherein the nucleic acid is tRNA.

[0400] 372. A vector comprising a nucleic acid molecule according to any one of items 351-360.

[0401] 373. A vector comprising a combination of nucleic acid molecules according to any one of items 361-371.

[0402] 374. A vector according to item 373, wherein the vector is bicistronic.

[0403] 375. The vector according to any one of items 373–375, wherein the vector is an expression vector.

[0404] 376. A vector according to any one of items 373-375, wherein the vector is a storage vector.

[0405] 377. A vector according to any one of items 373–375, wherein the vector is a cloning vector.

[0406] 378. A vector according to any one of items 373–375, wherein the vector is a transfer vector.

[0407] 379. A cell expressing the antibody or antigen-binding fragment thereof according to any one of items 278-333; or comprising the vector according to any one of items 372-378.

[0408] 380. The cell according to item 379, wherein the cell is a mammalian cell.

[0409] 381. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to any one of items 278-333, a nucleic acid according to any one of items 351-360, a combination according to any one of items 361-371, a vector according to any one of items 372-378, or a cell according to items 379-380, and a pharmaceutically acceptable excipient, diluent or carrier.

[0410] 382. The pharmaceutical composition according to item 381, wherein the pharmaceutical composition comprises at least two different anti-rabies virus antibodies or antigen-binding fragments thereof according to any one of items 278-333.

[0411] 383. The pharmaceutical composition according to item 382, ​​wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to different epitopes on glycoprotein G of RABV.

[0412] 384. The pharmaceutical composition according to claim 383, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to antigenic site I of glycoprotein G of RABV and bind to antigenic site III of glycoprotein G of RABV.

[0413] 385. A pharmaceutical composition according to any one of items 382-384, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0414] 386. The pharmaceutical composition according to claim 385, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0415] 387. The pharmaceutical composition according to any one of items 382-386, wherein the at least two different anti-rabies virus antibodies or antigen-binding fragments thereof are contained in the pharmaceutical composition in equimolar amounts.

[0416] 388. Use for (i) prevention, particularly post-exposure prophylaxis, treatment.

[0417] 389. An antibody or antigen-binding fragment thereof according to any one of items 278-333, a nucleic acid according to any one of items 351-360, a combination according to any one of items 361-371, a vector according to any one of items 372-378, a cell according to any one of items 379-380, or a pharmaceutical composition according to any one of items 381-387 for use in (i) preventing, in particular post-exposure prophylaxis, treating or attenuating RABV and / or non-RABV lyssavirus infection; (ii) vaccinating against RABV and / or non-RABV lyssavirus infection; or (iii) diagnosing RABV and / or other lyssavirus infection.

[0418] 390. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 389, wherein the pharmaceutical composition is administered as defined in items 1-64.

[0419] 391. An antibody or antigen-binding fragment thereof according to any one of items 278–333, a nucleic acid according to any one of items 351–360, a combination according to any one of items 361–371, a vector according to any one of items 372–378, a cell according to any one of items 379–380, or a pharmaceutical composition according to any one of items 381–387 for use in preventing or attenuating infection with a lyssavirus after exposure.

[0420] 392. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 391, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered up to seven days, or up to five days after infection.

[0421] 393. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for the use according to item 391 or 392, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered in combination with a vaccine, an antiviral agent, interferon-α and / or ketamine.

[0422] 394. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 393, wherein the vaccine is a rabies vaccine.

[0423] 395. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 393 or 394, wherein the antiviral agent is ribavirin.

[0424] 396. An antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to any one of items 391-395, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered in a standard PEP regimen.

[0425] 397. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 396, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered in combination with a vaccine in a standard PEP regimen.

[0426] 398. The antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to item 396 or 397, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered only during the first treatment of the standard PEP regimen.

[0427] 399. An antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to any one of items 391-398, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered 1 to 6 days, or 2 to 5 days after infection.

[0428] 400. An antibody or antigen-binding fragment thereof, nucleic acid, combination, vector, cell, or pharmaceutical composition for use according to any one of items 391-398, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition is administered without concomitant administration of a vaccine and / or without subsequent administration of a vaccine.

[0429] 401. A kit of parts comprising at least one antibody or antigen-binding fragment thereof according to any of items 278-333, a nucleic acid according to any of items 351-360, a combination according to any of items 361-371, a vector according to any of items 372-378, a cell according to any of items 379-380, or a pharmaceutical composition according to any of items 381-387.

[0430] 402. The kit of parts according to item 401, wherein the kit of parts comprises at least two different anti-rabies virus antibodies or antigen-binding fragments thereof as defined in any one of items 278-333.

[0431] 403. The kit of parts according to item 402, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to different epitopes on glycoprotein G of RABV.

[0432] 404. The kit of parts according to item 403, wherein the at least two antibodies or antigen-binding fragments thereof specifically bind to antigenic site I of glycoprotein G of RABV and bind to antigenic site III of glycoprotein G of RABV.

[0433] 405. A kit of parts according to any one of items 402-404, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 93-97 and 99, or to the amino acid sequences of SEQ ID NOs: 93-96 and 98-99, respectively; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises heavy chain CDRH1, CDRH2 and CDRH3 amino acid sequences and light chain CDRL1, CDRL2 and CDRL3 amino acid sequences, which are at least 80% or at least 90% identical to the amino acid sequences of SEQ ID NOs: 165-169 and 171, or to the amino acid sequences of SEQ ID NOs: 165-168 and 170-171, respectively.

[0434] 406. A kit of parts according to item 405, wherein one of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 107 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 108; and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof comprises a heavy chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 179 and a light chain variable region having at least 80% or at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 180.

[0435] 407. A method for treating or attenuating a lyssavirus infection in a subject, wherein the method comprises administering to a subject in need thereof an antibody or antigen-binding fragment thereof as defined in any one of items 278–333, a nucleic acid according to any one of items 351–360, a combination according to any one of items 361–371, a vector according to any one of items 372–378, a cell according to any one of items 379–380, or a pharmaceutical composition according to any one of items 381–387.

[0436] 408. The method according to item 407, wherein the antibody or antigen-binding fragment thereof, or the pharmaceutical composition

[0437] (i) administered into the central nervous system (CNS); and

[0438] (ii) is given peripherally.

[0439] 409. The method of item 407 or 408, wherein the subject is a human subject.

[0440] 410. The method of item 407 or 408, wherein the subject is an animal subject.

[0441] 411. The method of item 410, wherein the subject is selected from cattle, dogs, cats, horses, goats, sheep, pigs, and rabbits.

[0442] The present invention, and in particular the items summarized above, is described in more detail below. DETAILED DESCRIPTION

[0443] Although the present invention is described in detail below, it should be understood that the present invention is not limited to the specific methods, protocols and reagents described herein, as they may vary. It should also be understood that the terminology used herein is not intended to limit the scope of the present invention, which will be limited only by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art.

[0444] Hereinafter, the key elements of the present invention will be described. These key elements are listed together with specific embodiments, but it should be understood that they can be combined in any manner and in any number to produce other embodiments. The examples and embodiments described in various aspects should not be interpreted as limiting the present invention to the embodiments only explicitly described. This specification should be understood to support and encompass embodiments that combine the embodiments explicitly described with any number of disclosed and / or aspects. In addition, any arrangement and combination of all described key elements in this application should be considered to be disclosed by the specification of this application, unless the context otherwise indicates.

[0445] Throughout this specification and the appended claims, unless the context requires otherwise, the term "comprise" and variations such as "comprises" and "comprising" will be understood to imply the inclusion of the recited members, integers or steps but not the exclusion of any other unrecited members, integers or steps. The term "consisting of is a specific embodiment of the term "comprising" in which any other unrecited members, integers or steps are excluded. In the context of the present invention, the term "comprising" encompasses the term "consisting of. The term "comprising" thus encompasses "including" as well as "consisting of, for example, a composition "comprising" X may consist exclusively of X or may include some additional composition, such as X+Y.

[0446] The terms "a," "an," and "the," and similar references used in the context of describing the invention (particularly in the context of the claims) are to be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The recitation of ranges of values ​​herein is merely intended to serve as a shorthand method of referring individually to each individual value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

[0447] The term "substantially" does not exclude "completely", for example, a composition that is "substantially free of" Y may be completely free of Y. If necessary, the term "substantially" may be omitted from the definition of the present invention.

[0448] The term "about" with respect to a value x means x ± 10%.

[0449] The term "disease" as used herein is intended to be generally synonymous with the terms "disorder" and "condition" (as in medical condition) and are used interchangeably because they all reflect an abnormal condition of the human or animal body or one of its parts that impairs normal function, is usually manifested by distinctive signs and symptoms, and causes the human or animal to have a reduced lifespan or quality of life.

[0450] As used herein, "treatment" with reference to a subject or patient is intended to include preventing (reducing the occurrence), prophylaxis, attenuation, amelioration, and therapy. The terms "subject" or "patient" are used interchangeably herein to refer to all mammals, particularly humans. Examples of subjects include humans, cows, dogs, cats, horses, goats, sheep, pigs, and rabbits. For example, the patient is a human.

[0451] As used herein, the terms "antigen-binding fragment," "fragment," and "antibody fragment" are used interchangeably and refer to any fragment of an antibody that retains the antigen-binding activity of the antibody. Examples of antibody fragments include, but are not limited to, single-chain antibodies, Fab, Fab', F(ab')2, Fv, or scFv. Furthermore, the term "antibody" as used herein includes both antibodies and antigen-binding fragments thereof.

[0452] As used herein, the term "antibody" encompasses various forms of antibodies, including but not limited to whole antibodies, antibody fragments, specifically antigen-binding fragments, human antibodies, chimeric antibodies, humanized antibodies, recombinant antibodies, and genetically engineered antibodies (variants or mutant antibodies), as long as the characteristic properties according to the present invention are retained. For example, the antibody is a human antibody and / or a monoclonal antibody, specifically a recombinant human monoclonal antibody. For example, the antibody can be a monoclonal antibody. This includes the administration of more than one (such as two) monoclonal antibodies.

[0453] Human antibodies are well known in the art (van Dijk, MA, and van de Winkel, JG, Curr. Opin. Chem. Biol. 5 (2001) 368-374). Human antibodies can also be produced in transgenic animals (e.g., mice) that are able to produce a full set or selective human antibodies in the absence of endogenous immunoglobulin production after immunization. Transferring the human germline immunoglobulin gene array in such germline mutant mice will result in the production of human antibodies after antigen challenge (see, e.g., Jakobovits, A. et al., Proc. Natl. Acad. Sci. USA 90 (1993) 2551-2555; Jakobovits, A. et al., Nature 362 (1993) 255-258; Bruggemann, M. et al., Year Immunol. 7 (1993) 3340). Human antibodies can also be produced in phage display libraries (Hoogenboom, H.R. and Winter, G., J. Mol. Biol. 227 (1992) 381-388; Marks, J.D. et al., J. Mol. Biol. 222 (1991) 581-597). The techniques of Cole et al. and Boerner et al. can also be used to prepare human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); and Boerner, P. et al., J. Immunol. 147 (1991) 86-95). Typically, human monoclonal antibodies are prepared by immortalizing modified EBV-B cells, as described in Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR, Murphy BR, Rappuoli R, Lanzavecchia A. (2004): An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus. Nat Med. 10 (8): 871-5. The term "human antibody" as used herein also includes, for example, antibodies that have been modified in the constant and / or variable regions to produce the characteristics of the invention as described herein. As used herein, the term "variable region" (light chain variable region (V L ), heavy chain variable region (V H)) represents each of the light and heavy chain pairs that are directly involved in binding the antibody to the antigen.

[0454] The antibodies for use according to the present invention can have any isotype (e.g., IgA, IgG, IgM, i.e., α, γ, or μ heavy chains), such as IgG. Within the IgG isotype, the antibodies can be of the IgG1, IgG2, IgG3, or IgG4 subclass, such as IgG1. The antibodies can have κ or λ light chains.

[0455] For example, the antibody or antigen-binding fragment thereof for use according to the present invention is a purified antibody, a single chain antibody, Fab, Fab', F(ab')2, Fv or scFv.

[0456] The antibody of purposes according to the present invention can be, for example, a human antibody, a monoclonal antibody, a human monoclonal antibody, a recombinant antibody or a purified antibody. The fragment of the antibody usually retains the antigen-binding activity of the antibody. Such fragments include, but are not limited to, single-chain antibodies, Fab, Fab', F(ab')2, Fv or scFv. Although the specification, including the claims, may clearly relate to antigen-binding fragments (one or more), antibody fragments (one or more), variants (one or more) and / or derivatives (one or more) of antibodies in some places, it should be understood that the term "antibody" includes all classes of antibodies, i.e., antigen-binding fragments (one or more), antibody fragments (one or more), variants (one or more) and derivatives (one or more) of antibodies.

[0457] Fragments of antibodies for use according to the present invention can be obtained from antibodies by methods including enzymatic digestion using enzymes such as pepsin or papain, and / or by chemical reduction cleavage of disulfide bonds. Alternatively, fragments of antibodies can be obtained by cloning and expressing portions of the sequences of the heavy or light chains. Antibody "fragments" include Fab, Fab', F(ab')2, and Fv fragments. The present invention also encompasses single-chain Fv fragments (scFv) derived from the heavy and light chains of antibodies for use according to the present invention. For example, scFv comprises the CDRs of antibodies for use according to the present invention. Also included are heavy or light chain monomers and dimers, single domain heavy chain antibodies, single domain light chain antibodies, and single-chain antibodies, such as single-chain Fvs, in which the heavy and light chain variable domains are connected by a peptide connector.

[0458] The antibody fragment of purposes according to the present invention can give monovalent or multivalent interaction and be included in the multiple structure described above.For example, scFv molecule can be synthesized to create trivalent " three-chain antibody " or tetravalent " four-chain antibody (tetrabody) ".ScFv molecule can include the structural domain in the Fc district that causes bivalent mini-antibody (minibody)."In addition, CDR or variable region sequence can be the component of multispecific molecule, and wherein CDR or variable region sequence targeting epitope and other district of molecule are bonded to other targets.Exemplary molecule includes but is not limited to bispecific Fab2, trispecific Fab3, bispecific scFv and diabody (Holliger and Hudson, 2005, Nature Biotechnology 9:1126-1136).

[0459] The antibodies can be provided in purified form. Typically, the antibodies will be present in a composition that is substantially free of other polypeptides. As used herein, "substantially free of other polypeptides" means that less than 90% (by weight), typically less than 60%, such as less than 50%, of the composition is composed of other polypeptides.

[0460] Antibodies can be immunogenic in humans and / or non-human (or xenogeneic) hosts, such as mice. For example, an antibody can have an idiotype that is immunogenic in a non-human host but not in a human host. Antibodies for human use include those that cannot be easily isolated from hosts such as mice, goats, rabbits, rats, non-primate mammals, and the like and that cannot generally be obtained by humanization or from xenogeneic mice.

[0461] As used herein, "neutralizing antibodies" are antibodies that can neutralize, i.e., prevent, inhibit, reduce, hinder, or interfere with the ability of a pathogen to initiate and / or perpetuate an infection in a host. The terms "neutralizing antibody" and "neutralizing antibody(ies)" are used interchangeably herein. These antibodies can be used alone or in combination, after appropriate formulation, as a prophylactic or therapeutic agent, in conjunction with active immunization, as a diagnostic tool, or as a production tool as described herein.

[0462] Doses are usually expressed with respect to body weight. Thus, a dose expressed as [g, mg or other unit] / kg (or g, mg, etc.) usually refers to [g, mg or other unit] " / kg (or g, mg, etc.) body weight", even if the term "body weight" is not explicitly mentioned.

[0463] The term "specifically binds" and similar references do not encompass non-specific adhesion.

[0464] As used herein, the term "vaccine" is generally understood to be a preventive or therapeutic substance that provides at least one antigen, such as an immunogen. Antigens or immunogens can be derived from any substance suitable for vaccination. For example, antigens or immunogens can be derived from pathogens, such as from bacteria or virus particles, or from tumors or cancerous tissue. Antigens or immunogens stimulate the body's adaptive immune system to provide an adaptive immune response. Specifically, "antigen" or "immunogen" generally refers to a substance that can be recognized by the immune system, such as the adaptive immune system, and that is capable of triggering an antigen-specific immune response, such as by forming antibodies and / or antigen-specific T cells as part of an adaptive immune response. Typically, an antigen can be or can include a peptide or protein that can be presented to T cells via MHC.

[0465] As used herein, "sequence variant" refers to any alteration of a reference sequence, whereby the reference sequence is a sequence listed in the "Table of Sequences and SEQ ID Numbers" (Sequence Listing), i.e., any one of SEQ ID NO: 1 to SEQ ID NO: 218. Thus, the term "sequence variant" includes nucleotide sequence variants and amino acid sequence variants. Specifically, the sequence variants referred to herein are functional sequence variants, i.e., sequence variants that maintain a biological function, such as an antibody. In the context of the present invention, such maintained biological functions are, for example, neutralization of lyssavirus infection and / or binding of an antibody to (a specific epitope of) glycoprotein G of a lyssavirus (e.g., RABV). As used herein, a sequence variant has, for example, at least 70% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 75% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 80% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 85% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 88% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 90% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 92% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 95% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 96% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 97% sequence identity with the corresponding reference sequence. For example, a sequence variant has at least 98% sequence identity or at least 99% sequence identity with the corresponding reference sequence.

[0466] The term "sequence variant" includes specifically variants that comprise mutations and / or substitutions compared to a reference sequence. Exemplary variants of the Fc portion sequence include, but are not limited to, variants having an L to A substitution at position CH2 4, position CH2 5, or both.

[0467] Sequence identity is usually calculated over the entire length of a reference sequence (i.e., the sequence described in this application). Percent identity as referred to herein can be determined, for example, using BLAST using the default parameters specified by NCBI (National Center for Biotechnology Information; http: / / www.ncbi.nlm.nih.gov / ) [Blosum 62 matrix; gap open penalty = 11 and gap extension penalty = 1].

[0468] As used herein, "nucleotide sequence variants" have altered sequences in which one or more of the nucleotides in the reference sequence are deleted, or substituted, or one or more nucleotides are inserted into the sequence of the reference nucleotide sequence. Nucleotides are referred to herein by standard one-letter designations (A, C, G, or T). Due to the degeneracy of the genetic code, "nucleotide sequence variants" may result in changes in the corresponding reference amino acid sequence, i.e., "amino acid sequence variants," or may not result in "amino acid sequence variants." Example sequence variants are nucleotide sequence variants that do not result in amino acid sequence variants (silent mutations), but other non-silent mutations are also within the scope of the present invention, specifically mutated nucleotide sequences that result in an amino acid sequence having at least 80% or at least 90%, such as at least 95% or 99% sequence identity to the reference sequence. It should be understood that in all examples used herein, "at least 80% identity" includes at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and 100% identity. Similarly, "at least 90% identity" includes at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and 100% identity.

[0469] "Amino acid sequence variants" have altered sequences in which one or more amino acids in a reference sequence are deleted or substituted, or one or more amino acids are inserted into the sequence of a reference amino acid sequence. As a result of the alterations, the amino acid sequence variant has an amino acid sequence that is at least 80% or at least 90% identical to the reference sequence, such as at least 95% or at least 99% identical. A variant sequence with at least 90% identity has no more than 10 alterations, i.e., any combination of deletions, insertions, or substitutions, per 100 amino acids of the reference sequence. It should be understood that in all instances used herein, "at least 80% identity" includes at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and 100% identity. Likewise, "at least 90% identity" includes at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and 100% identity.

[0470] For example, an amino acid substitution is a conservative amino acid substitution, wherein the substituted amino acid has similar structural properties or chemical properties to the corresponding amino acid in the reference sequence. For example, a conservative amino acid substitution involves replacing one aliphatic or hydrophobic amino acid, such as alanine, valine, leucine, and isoleucine, with another; replacing one hydroxyl-containing amino acid, such as serine and threonine, with another; replacing one acidic residue such as glutamic acid or aspartic acid with another; replacing one amide-containing residue such as asparagine and glutamine with another; replacing one aromatic residue such as phenylalanine and tyrosine with another; replacing one basic residue such as lysine, arginine, and histidine with another; and replacing one small amino acid such as alanine, serine, threonine, methionine, and glycine with another. However, non-conservative amino acid substitutions are also possible.

[0471] Amino acid sequence insertions include amino-terminal and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing one hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include fusions of the N-terminus or C-terminus of an amino acid sequence to a reporter molecule or enzyme.

[0472] In some cases, the alteration of the sequence variant does not abolish the functionality of the corresponding reference sequence, in the present case, for example, the functionality of the sequence of the antibody or antigen-binding fragment thereof to bind to the same epitope and / or fully neutralize infection by lyssavirus (such as RABV). Guidance in determining which nucleotide and amino acid residues, respectively, can be substituted, inserted or deleted without abolishing such functionality is found by using computer programs well known in the art.

[0473] As used herein, "derived from" a nucleic acid sequence or amino acid sequence of a specified nucleic acid, peptide, polypeptide or protein refers to the source of the nucleic acid, peptide, polypeptide or protein. For example, a nucleic acid or amino acid sequence derived from a specific sequence has an amino acid sequence that is substantially identical to the sequence or portion thereof from which it is derived, whereby "substantially identical" includes sequence variants as defined above. For example, a nucleic acid sequence or amino acid sequence derived from a specific peptide or protein is derived from a corresponding domain in the specific peptide or protein. Thus, "corresponding" specifically refers to the same functionality. For example, an "extracellular domain" corresponds to another "extracellular domain" (of another protein), or a "transmembrane domain" corresponds to another "transmembrane domain" (of another protein). Thus, the "corresponding" portions of peptides, proteins and nucleic acids are readily identified by those of ordinary skill in the art. Similarly, sequences that are "derived from" other sequences are generally readily identified by those of ordinary skill in the art as having their origin in the sequence.

[0474] For example, the nucleic acid sequence or amino acid sequence derived from another nucleic acid, peptide, polypeptide or protein can be identical with the starting nucleic acid, peptide, polypeptide or protein from which it is derived. However, the nucleic acid sequence or amino acid sequence derived from another nucleic acid, peptide, polypeptide or protein can also have one or more sudden changes relative to the starting nucleic acid, peptide, polypeptide or protein from which it is derived. Specifically, the nucleic acid sequence or amino acid sequence derived from another nucleic acid, peptide, polypeptide or protein can be a functional sequence variant as described above of the starting nucleic acid, peptide, polypeptide or protein from which it is derived. For example, in a peptide / protein, one or more amino acid residues can be substituted by other amino acid residues, or one or more amino acid residues can be inserted or deleted.

[0475] As used herein, the term "mutation" refers to a change in a nucleic acid sequence and / or an amino acid sequence relative to a reference sequence (e.g., a corresponding genomic sequence). Mutations, for example, compared to genomic sequences, can be (naturally occurring) somatic mutations, spontaneous mutations, induced mutations (e.g., mutations induced by enzymes, chemicals, or radiation), or mutations obtained by site-directed mutagenesis (molecular biology methods for producing specific and intentional changes in nucleic acid sequences and / or amino acid sequences). Therefore, the term "mutation" or "mutating" will be understood to also include, for example, physically generating mutations in a nucleic acid sequence or an amino acid sequence. Mutations include substitutions, deletions, and insertions of one or more nucleotides or amino acids, as well as inversions of several consecutive nucleotides or amino acids. In order to achieve mutations in an amino acid sequence, mutations can be introduced into the nucleotide sequence encoding the amino acid sequence to express (recombinant) mutated polypeptides. Mutation can be achieved, for example, by changing (e.g., by site-directed mutagenesis) the codons of a nucleic acid molecule encoding one amino acid to produce codons encoding a different amino acid, or by synthesizing sequence variants—e.g., by knowing the nucleotide sequence of a nucleic acid molecule encoding a polypeptide, and by designing the synthesis of a nucleic acid molecule comprising a nucleotide sequence encoding a variant of the polypeptide without mutating one or more nucleotides of the nucleic acid molecule.

[0476] As used herein, "rabies" refers to the disease of rabies. Rabies is caused by various lyssaviruses, including lyssavirus and other lyssaviruses, such as European bat lyssavirus.

[0477] Lyssavirus has spiral symmetry, has the length of about 180nm and the cross section of about 75nm.These viruses are enveloped and have single-stranded negative sense RNA genome.Inherited information is packaged as ribonucleoprotein complex, and wherein RNA is closely combined by viral nucleoprotein.The RNA genome coding sequence of virus is highly conserved five kinds of genes: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and viral RNA polymerase (L).

[0478] The lyssavirus genus is subdivided into four phylogroups, 14 species, and four experimental new species. Phylogroup I includes species: rabies virus (RABV), European bat lyssavirus types 1 (EBLV-1) and 2 (EBLV-2), Duvenhage virus (DUVV), Australian bat lyssavirus (ABLV), Aravanvirus (ARAV), Khujand virus (KHUV), Bokeloh bat lyssavirus (BBLV), and Irkut virus (IRKV). Phylogroup II includes Lagos bat virus (LBV), Mokola virus (MOKV), and Shimoni bat virus (SHIV or SHIBV). The remaining viruses, West Caucasian bat virus (WCBV) and Ikoma lyssavirus (IKOV), could not be included in either of these two genetic lineages but were classified as genetic lineages III and IV, respectively (Bourhy, H. et al. Journal of Clinical Microbiology 30, 2419–2426, 1992; Bourhy, H. et al. Virology 194, 70–81, 1993; Amengual, B. et al. J Gen. Virol 78, 2319–2328, 1997; Kuzmin, IV et al. Virus Res 149, 197–210, 2010; Badrane, H. et al. J Virol 75, 3268–3276, 2001; Marston, DA et al. Emerg Infect Dis 18, 664–667, 2012; Delmas O, Holmes EC, Talbi C, Larrous F, Dacheux L, Bouchier C, Bourhy H. Genomic diversity and evolution of the lyssaviruses. PLoS One. 2008 Apr30;3(4):e2057).Importantly, all of these lyssavirus species have essentially caused death in humans and / or animals (Badrane, H. et al. J Virol 75, 3268–3276, 2001; Fooks AR, Cliquet F, Finke S, Freuling C, Hemachudha T, Mani RS, Müller T, Nadin-Davis S, Picard-Meyer E, Wilde H, Banyard AC. Rabies. Nat Rev Dis Primers. 2017 Nov 30; 3: 17091).

[0479] Rabies virus (RABV) is the first of fourteen Lyssavirus genotypes to be identified. Rabies virus is classified as a large, enveloped, single-stranded RNA virus, and the genome of rabies virus encodes five viral proteins: RNA-dependent RNA polymerase (L); nucleoprotein (N); phosphorylated protein (P); matrix protein (M), which is located on the inside of the viral envelope; and outer surface glycoprotein (G). G protein (62-67 kDa) is a type I glycoprotein composed of 505 amino acids with two to four potential N-glycosylation sites. G protein covers the outer surface of the virion envelope and is the only target antigen that can induce antibodies that neutralize the virus.

[0480] Several documents are cited throughout the text of this specification. Each of the documents cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, is hereby incorporated by reference in its entirety. Nothing disclosed herein is to be construed as an admission that the present invention is not entitled to antedate such disclosure by virtue of prior invention.

[0481] It will be understood that the present invention is not limited to the specific methods, protocols, and reagents described herein, as they may vary. It will also be understood that the terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the scope of the present invention, which will be limited only by the appended claims. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art.

[0482] Anti-rabies virus antibodies administered to the CNS and peripherally

[0483] In a first aspect, an anti-rabies virus antibody or an antigen-binding fragment thereof is provided for use in treating rabies virus infection, wherein the antibody or antigen-binding fragment thereof is

[0484] (i) administered into the central nervous system (CNS); and

[0485] (ii) is given peripherally.

[0486] Disclosed herein are methods for treating symptomatic rabies virus infection even after symptoms of rabies virus infection develop, when anti-rabies virus antibodies are (i) administered into the CNS; and (ii) administered peripherally (outside the CNS), as shown in the accompanying Examples. Without being limited by any theory, the effect of passively administering anti-rabies virus antibodies may inactivate the virus in the periphery, thereby limiting its access to nerve endings. Once rabies virus reaches the central nervous system (CNS) tissues, circulating anti-rabies virus antibodies will have a lower effect due to their limited ability to cross the blood-brain barrier. On the other hand, without being limited by any theory, the presence of anti-rabies virus antibodies only in the CNS (i.e., the absence of antibodies in the periphery) may not be sufficient for successful therapeutic treatment of symptomatic rabies.

[0487] Antibodies against rabies virus and their antigen-binding fragments are known in the art. For example, Ilina EN, Larina MV, Aliev TK, Dolgikh DA, Kirpichnikov MP. Recombinant Monoclonal Antibodies for Rabies Post-exposure Prophylaxis. Biochemistry (Mosc). 2018 Jan; 83(1): 1-12. doi: 10.1134 / S0006297918010017 provides a review. Examples of anti-lyssavirus antibodies and antigen-binding fragments thereof are described in WO 2016 / 078761 and De Benedictis et al., 2016 (De Benedictis P, Minola A, Rota Nodari E, Aiello R, Zecchin B, Salomoni A, Foglierini M, Agatic G, Vanzetta F, Lavenir R, Lepelletier A, Bentley E, Weiss R, Cattoli G, Capua I, Sallusto F, Wright E, Lanzavecchia A, Bourhy H, Corti D. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol Med. 2016 Apr 1; ​​8(4):407-21. doi: 10.15252 / emmm.201505986), which are incorporated by reference.

[0488] According to the present invention, the anti-rabies virus antibody or antigen-binding fragment thereof (i) is administered into the central nervous system (CNS) and (ii) is administered peripherally. In general, the anti-rabies virus antibody administered into the central nervous system (CNS) and the anti-rabies virus antibody administered peripherally can be the same anti-rabies virus antibody or different anti-rabies virus antibodies (or the same or different combination (one or more) of two or more anti-rabies virus antibodies). For example, the same anti-rabies virus antibody (or the same combination of two or more anti-rabies virus antibodies) is administered into the central nervous system (CNS) and is administered peripherally.

[0489] As used herein, the term "peripherally" used in the context of a route of administration (e.g., peripheral administration) refers to any route of administration outside the central nervous system (CNS) and the blood-brain barrier (BBB). Thus, the terms "peripherally," "peripheral," and "peripheral" as used herein should be understood with respect to the CNS / BBB and generally refer to those parts of the body that are "outside the BBB" and other than the CNS.

[0490] As used herein, the expression "into the central nervous system" used in the context of a route of administration (e.g., administration into the CNS) includes any route of administration that reaches (enters) brain and spinal cord tissues and enters the cerebrospinal fluid (CSF) (i.e., anything "within the BBB").

[0491] In general, the central nervous system (also referred to as "CNS") is a part of the nervous system that consists of the brain and spinal cord. The retina, optic nerve (cranial nerve II), olfactory nerve (cranial nerve I), and olfactory epithelium are part of the brain. The olfactory epithelium is the only central nervous system tissue that is in direct contact with the environment.

[0492] The CNS and its extracellular fluid are separated from the circulating blood by a highly selective semipermeable membrane, the blood-brain barrier (also known as the "BBB"). The BBB is formed by endothelial cells, which restrict the diffusion of small objects (e.g., bacteria) and large molecules into the cerebrospinal fluid (CSF), while allowing the passage of water, certain gases, and fat-soluble (hydrophobic) molecules (O2, CO2, hormones) by passive diffusion, as well as the selective transport of molecules that are critical for neural function, such as glucose and amino acids. However, larger hydrophilic molecules, such as antibodies, are generally prevented from crossing the BBB.

[0493] Since antibodies are generally unable to cross the blood-brain barrier, the present invention includes (i) administering antibodies peripherally (i.e., to any part of the body outside the CNS / BBB) and (ii) administering antibodies into the CNS (i.e., to any part of the body "inside" the CNS / BBB). In this way, anti-rabies virus antibodies can exert their effects on both sides of the BBB.

[0494] Administration into the CNS generally includes administration into brain tissue or spinal cord tissue and administration into cerebrospinal fluid (CSF). For example, Pathan SA, Iqbal Z, Zaidi SM, Talegaonkar S, Vohra D, Jain GK, Azeem A, Jain N, Lalani JR, Khar RK, Ahmad FJ. CNS drug delivery systems: novel approaches. Recent Pat Drug Deliv Formul. 2009 Jan; 3 (1): 71-89 (which is incorporated herein by reference) describes examples of administration routes into the CNS.

[0495] In general, administration to the CNS can be performed by injection or infusion (e.g., by using a suitable needle or catheter). For repeated or continuous administration, a reservoir and / or a miniature pump can be used. The route of administration into the CNS can be selected from intrathecal administration, epidural administration, intraventricular administration, intracerebral administration, nasal administration, ocular administration, intranasal administration, and perimedullary administration.

[0496] For example, anti-rabies virus antibodies are administered into the cerebrospinal fluid (intra-CSF administration). Cerebrospinal fluid (CSF) is a colorless, transparent body fluid found in the brain and spinal cord. CSF occupies the subarachnoid space (between the arachnoid membrane and the pia mater) and the ventricular system surrounding and within the brain and spinal cord. It fills the ventricles, cisterns, sulci, and the central canal of the spinal cord.

[0497] The example of administration route in CSF includes intrathecal administration, intraventricular administration, and epidural administration. For example, anti-rabies virus antibodies can be delivered to the CSF of the spinal cord by intrathecal administration or epidural administration. For example, anti-rabies virus antibodies can be delivered to the CSF of the brain by intraventricular administration. For repeated or continuous administration, a reservoir and / or a micropump can be used. For example, the Ommaya reservoir can be used for intraventricular (ICV) administration (Ommaya AK. Subcutaneous reservoir and pump for sterile access to ventricular cerebrospinal fluid. Lancet. 1963 Nov 9; 2 (7315): 983-4). The Ommaya reservoir includes a mushroom-shaped dome made of silicone rubber, which is connected to a catheter inserted into the lateral ventricle. The Ommaya reservoir is implanted subcutaneously and is a compressible pump.

[0498] Anti-rabies virus antibodies can also be administered directly into brain tissue (intracerebral administration). For example, anti-rabies virus antibodies can be administered locally to selected brain regions, for example, so that afflicted brain regions can be directly targeted.

[0499] Another option for administration into the CNS is intranasal administration, such as described in US 5624898 A, WO 00 / 33813, and in Dhuria SV, Hanson LR, Frey WH 2nd. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci. 2010 Apr; 99 (4): 1654-73. doi: 10.1002 / jps.21924. Intranasal delivery can be achieved by a nasal delivery device, such as a spray, a nasal dropper, or a needle-free syringe. For example, a nasal delivery device is used that is designed to deposit the formulation applied nasally specifically into the olfactory region (olfactory epithelium), such as a bidirectional technique. TM (Bi-DirectionalTechnology TM ) ) OptiNose, POD device (Impel NeuroPharma) or Controlled Particle Dispersion (CPD TM ) technologies, such as ViaNase TM Device (Kurve Technology).

[0500] Another option for administration to the CNS is nasal or ocular administration, such as described in CA 2560798A1. Thus, the substance is administered via the olfactory nerve or the optic nerve. Other nasal and ocular administration methods are described in Pathan SA, Iqbal Z, Zaidi SM, Talegaonkar S, Vohra D, Jain GK, Azeem A, Jain N, Lalani JR, Khar RK, Ahmad FJ. CNS drug delivery systems: novel approaches. Recent Pat Drug Deliv Formul. 2009 Jan; 3(1): 71-89.

[0501] Another option for administration into the CNS is perimedullar administration, such as described in Tobinick EL. Perispinal Delivery of CNS Drugs. CNS Drugs. 2016 Jun; 30(6): 469-80. doi: 10.1007 / s40263-016-0339-2. Perimedullary administration can optionally be performed by perimedullar injection. Perimedullary administration is designed to utilize the cerebrospinal venous system (CSVS) and deliver substances to the anatomical region behind the ligamentum flavum, which is drained by the extravertebral venous plexus (EVVP), a branch of the CSVS.

[0502] According to the present invention, anti-rabies virus antibodies or antigen-binding fragments thereof (in addition to administration into the CNS) are also administered peripherally, i.e., "outside" the central nervous system (CNS) and blood-brain barrier (BBB) ​​in vivo. Thus, any administration route that does not target the CNS and / or bypass the BBB can be used for peripheral administration. It should be understood that antibodies or antigen-binding fragments thereof administered peripherally are not administered into the CNS (as described above).

[0503] Typically, the antibody or its Fab administered peripherally is administered systemically or locally (e.g., in the periphery). Systemic administration routes generally include enteral administration routes and parenteral administration routes. Examples of enteral administration include oral administration and rectal administration. Examples of parenteral administration include intravenous, intramuscular, intraarterial, subcutaneous, intradermal, transdermal, and intraperitoneal routes. Approaches for local administration generally include, for example, local administration routes, and specifically intradermal administration, transdermal administration, subcutaneous administration, or intramuscular administration.

[0504] In a specific embodiment, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered intravenously (iv), intramuscularly (im), subcutaneously (sc), or intradermally. For example, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered subcutaneously. For example, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered intradermally. For example, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered intramuscularly. For example, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered intravenously. For example, the anti-rabies virus antibody or antigen-binding fragment thereof administered peripherally is administered intravenously (iv) or intramuscularly (im). Thus, for example, the anti-rabies virus antibody is formulated in liquid (or sometimes solid) form.

[0505] For example, the antibody or its antigen-binding fragment that is given peripherally is given at the lesion site." lesion site " is normally the body part that rabies virus enters in the body, for example the position that (dog or bat) bites. Should be understood that, giving at the lesion site does not necessarily mean that anti-rabies virus antibody must be given in the bite wound itself (this may disturb wound healing), and it is enough to give in the immediate vicinity usually. For example, (bite occurs) same muscle can be targeted for giving at the lesion site. For example, can give anti-rabies virus antibody intramuscularly, subcutaneously or intradermally at the lesion site (for example, same muscle that bites or corresponding skin).

[0506] According to the present invention, anti-rabies virus antibodies or antigen-binding fragments thereof are generally used to treat rabies virus infection. As used herein, the term "treat" refers to preventing, prophylaxis (such as post-exposure prophylaxis), therapy, cure, amelioration, and alleviation of rabies virus infection (and / or its symptoms). Administration of anti-rabies virus antibodies according to the present invention is very effective before and after the onset of symptoms of rabies virus infection.

[0507] However, since peripheral administration is usually more convenient for patients than administration to the CNS, the anti-rabies virus antibody according to the present invention is optionally used in more serious situations, such as after (supposed or confirmed) rabies virus infection, particularly, when (classical) post-exposure therapy is invalid or insufficient, or after the symptoms of rabies virus infection occur. Therefore, for example, antibody or its antigen-binding fragment is given for the first time after the (first) symptoms of rabies virus infection occur. Early symptoms include fever, anorexia, nausea, headache, general weakness or discomfort, and stinging, itching or local pain at the bite site. These symptoms particularly progress to one or more of the following symptoms relevant to brain dysfunction within a few days: vigorous exercise, uncontrolled excitement, fear of water, fear of heights, mental confusion, hyperactivity, the component part that cannot move the body, paralysis and loss of consciousness. For example, in the case of rabies, two different types of disease may develop after the virus attacks the CNS: furious rabies, whose symptoms include insomnia, anxiety, confusion, agitation, hallucinations, excessive salivation, dysphagia and hydrophobia; and paralytic rabies, in which the infected patient slowly becomes paralyzed and eventually falls into a coma. For example, the anti-lyssavirus antibody according to the present invention is (for the first time) administered as soon as possible after the (first) symptoms of lyssavirus infection occur (e.g., are observed).

[0508] For example, antibody or its Fab is for example given for the first time after being exposed to lyssavirus at least five days or at least six days. For example, antibody or its Fab is for example given for the first time after being exposed to lyssavirus at least seven days or at least eight days. This time frame is consistent with the occurrence of the first symptoms of the above-mentioned lyssavirus infection usually. In other examples, antibody or its Fab is for example given for the first time on the same day of being exposed to lyssavirus or at least one day after being exposed to lyssavirus. For example, antibody or its Fab can be for example given for the first time after being exposed to lyssavirus at least 0,1,2,3 or 4 days. In some embodiments, antibody or its Fab is given for the first time at least 5 days after being exposed to lyssavirus.

[0509] As described above, the antibody or antigen-binding fragment thereof according to the use of the present invention or the pharmaceutical composition for use of the present invention may be administered after the onset of the first symptoms, i.e., after the onset of symptoms. In some embodiments, the antibody or antigen-binding fragment thereof according to the use of the present invention or the pharmaceutical composition for use of the present invention may be administered no more than one week after the onset of symptoms. For example, the antibody or antigen-binding fragment thereof according to the use of the present invention or the pharmaceutical composition for use of the present invention may be administered no more than 6 days or 5 days after the onset of symptoms (e.g., 1 to 6 days or 2 to 5 days after the onset of symptoms). In some embodiments, the antibody or antigen-binding fragment thereof according to the use of the present invention or the pharmaceutical composition for use of the present invention may be administered no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 day after the onset of symptoms.

[0510] In general, as described herein, anti-rabies virus antibodies or antigen-binding fragments thereof can be administered to the CNS and peripherally at approximately the same time (concomitantly) or one after another (sequentially). In addition, anti-rabies virus antibodies or antigen-binding fragments thereof can be administered to the CNS and peripherally in the same pharmaceutical form (same type of preparation) or in different pharmaceutical forms (different types of preparations, e.g., one preparation is suitable for administration to the CNS, while another preparation is suitable for peripheral administration).

[0511] For example, can carry out periphery to give and be given in CNS in succession (sequentially).This means that periphery gives and is to be performed before and / or after giving in CNS.In giving in succession, the time between two types of giving (peripherally and entering in CNS) is for example no more than one week or no more than 3 days, such as no more than 2 days or no more than 24 hours.For example, carry out periphery to give and be given in CNS in the same day, and, for example, the time between the giving of the first component and the giving of the second component is no more than 6 hours or no more than 3 hours, such as no more than 2 hours or no more than 1 hour.

[0512] In some embodiments, peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS are performed at approximately the same time (simultaneously).

[0513] As used herein, "at about the same time" specifically refers to simultaneous administration or antibody is peripherally administered immediately after administration to the CNS, or antibody is administered to the CNS immediately after peripheral administration. It will be understood by those skilled in the art that "immediately after..." includes the time required for preparing to administer a second time--specifically, the time required to expose and disinfect the second administration position and the time required for appropriately preparing "administering means" (e.g., syringes, pumps, etc.). Simultaneous administration also includes the situation where peripheral administration and administration to the CNS overlap, or, for example, one type of administration (e.g., administration to the CNS or peripherally administered) occurs, for example, by infusion, over a long period of time (e.g., 30 min, 1 h, 2 h or even longer), and another type of administration is performed, for example, by injection, at a certain time during such a long period.

[0514] Specifically, an antibody or antigen-binding fragment thereof is administered peripherally while the antibody or antigen-binding fragment thereof is administered into the CNS. In other words, an antibody or antigen-binding fragment thereof is administered peripherally, for example, while the antibody or antigen-binding fragment thereof is administered into the CNS. For example, an antibody or antigen-binding fragment thereof can be administered peripherally (e.g., iv, im, sc, or intradermally) by (e.g., single) injection during administration of the antibody or antigen-binding fragment thereof into the CNS by (continuous) infusion.

[0515] For example, the anti-rabies virus antibody or its antigen-binding fragment can be peripherally administered once (single peripheral administration) or repeatedly administered, for example, by injection (e.g., iv, im, sc, or intradermal). Thus, in some embodiments, the anti-rabies virus antibody or its antigen-binding fragment is peripherally administered once (single peripheral administration). In another embodiment, the anti-rabies virus antibody or its antigen-binding fragment is peripherally administered repeatedly.

[0516] For example, the first peripheral administration of an antibody or its Fab and the first administration of the antibody or its Fab to CNS occur on the same day. As used herein, "first time" administration (peripherally or into CNS) refers to the first administration (for example, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more times of administration) of (i) repeated administration; or refers to the only administration (for example, only a single peripheral administration or only a single administration to CNS) in the presence of only a single administration. In other words, the term "first time" as used in this context does not imply that repeated administration must be present. For example, the first peripheral administration of an antibody or its Fab and the first administration of the antibody or its Fab to CNS occur on the same day, for example, at approximately the same time. For example, as described above, an antibody or its Fab can be administered peripherally, while the antibody or its Fab is administered to CNS.

[0517] In some embodiments, the anti-rabies virus antibody or antigen-binding fragment thereof is administered to the CNS by continuous administration, for example, for at least 15 minutes or at least 30 minutes, such as at least 1 hour or 6 hours, (e.g., at least 12 hours). In some embodiments, the antibody or antigen-binding fragment thereof is administered continuously to the CNS for at least 24 hours or at least 2 days, such as at least 3 days or at least 4 days (e.g., at least 5 days).

[0518] In some embodiments, the present invention provides the stabilization of rabies virus antibody or its Fab.For example, the stabilization of rabies virus antibody or its Fab is provided in the form of continuous administration.For example, the stabilization of rabies virus antibody or its Fab is provided in the form of continuous administration.For example, the stabilization of rabies virus antibody or its Fab is provided in the form of continuous administration.For example, the stabilization of rabies virus antibody or its Fab is provided in the form of continuous administration.For example, the stabilization of rabies virus antibody or its Fab is provided in the form of continuous administration.

[0519] For example, the antibody or antigen-binding fragment thereof is administered to the CNS every day or every two days, e.g., for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 days. Daily administration is achieved by continuous administration as described above or by repeated intermittent administration (one administration, e.g., a single injection per day).

[0520] In addition, the (monoclonal) antibody or its antigen-binding fragment according to the use of the present invention or contained in the pharmaceutical composition for use according to the present invention can be administered at a dose of 0.01 to 100 mg / kg or at a dose of 0.1 to 75 mg / kg, such as at a dose of 0.5 to 60 mg / kg or at a dose of 1 to 50 mg / kg. For example, for peripheral administration, the minimum dose can be 2 or 4 mg / kg, for example, a dose range of 2–45 mg / kg or 4–40 mg / kg can be used. In some embodiments, the minimum dose can be 10 or 20 mg / kg, such as 40 mg / kg, specifically for peripheral administration. For administration into the CNS, the minimum dose can be 0.2 or 0.4 mg / kg, for example, a dose range of 0.2–20 mg / kg or 0.4–10 mg / kg can be used. In some embodiments, the minimum dose can be 1 or 2 mg / kg, such as 4 mg / kg, specifically for administration into the CNS.

[0521] It will be understood that the above dosages relate to a single dose, such as a dose administered once (e.g., a single injection), or, if continuous administration is applied, to a dose administered daily (single daily dose). In addition, as described herein, if a combination of (monoclonal) antibodies is applied, the above dosages represent the "total" (i.e., the total amount of anti-rabies virus antibodies or antigen-binding fragments thereof as described herein). In this case, the amount of antibody can be evenly distributed, for example, if two different anti-rabies virus antibodies as described herein are used, each antibody can be administered at half the above dosage.

[0522] In general, "higher" doses are particularly useful if the exposure is severe and / or if treatment is initiated later than one or two days after exposure. As a general guideline, the later treatment is initiated after exposure or after the first symptoms develop, the higher the dose of the antibody or antigen-binding fragment thereof that can be used.

[0523] The lyssavirus infection to be treated by the present invention can be the infection of any lyssavirus. Technicians will select anti-lyssavirus antibodies according to the lyssavirus infection to be treated. In addition, widely neutralized anti-lyssavirus antibodies known in the art, which neutralize rabies virus (RABV) and a large amount of non-RABV lyssavirus infections. Such widely neutralized anti-lyssavirus antibodies are described in, for example, WO 2016 / 078761 and in De Benedictis et al. (De Benedictis P, Minola A, Rota Nodari E, Aiello R, Zecchin B, Salomoni A, Foglierini M, Agatic G, Vanzetta F, Lavenir R, Lepelletier A, BentleyE, Weiss R, Cattoli G, Capua I, Sallusto F, Wright E, Lanzavecchia A, Bourhy H, Corti D.2016), which are incorporated herein by reference. For example, the lyssavirus infection to be treated is rabies, and the anti-lyssavirus antibody or antigen-binding fragment thereof is an anti-RABV antibody or antigen-binding fragment thereof.

[0524] Typically, anti-lyssavirus antibodies or antigen-binding fragments thereof bind to lyssavirus glycoprotein G (also referred to as "G protein"), such as the G protein (glycoprotein G) of RABV. For example, the antibodies or antigen-binding fragments thereof according to the present invention bind to the G protein (glycoprotein G) of RABV and / or to the G protein (glycoprotein G) of non-RABV lyssaviruses.

[0525] The RNA genome of lyssavirus encodes five viral proteins: RNA-dependent RNA polymerase (L); nucleoprotein (N); phosphorylated protein (P); matrix protein (M) located on the inside of the viral envelope; and outer surface glycoprotein (G). G protein covers the outer surface of the virion envelope and can induce antibodies that neutralize the virus. G protein (62-67kDa) is a type I glycoprotein composed of 505 amino acids with two to four potential N-glycosylation sites. The sequence of lyssavirus glycoprotein G is known in the art and is described, for example, in Buthelezi SG, Dirr HW, Chakauya E, Chikwamba R, Martens L, Tsekoa TL, Stoychev SH, Vandermarliere E. The Lyssavirus glycoprotein: A key to cross-immunity. Virology. 2016 Nov; 498: 250-256. doi: 10.1016 / j.virol.2016.08.034 (specifically the supplementary material of Buthelezi et al., which provides a large number of lyssavirus glycoprotein G sequences).

[0526] Typically, the epitope to which an antibody binds can be linear (continuous) or conformational (discontinuous). In one embodiment, an antibody or antibody fragment thereof binds to a conformational epitope. A conformational epitope, for example, exists only under non-reducing conditions.

[0527] In some embodiments, the anti-rabies virus antibody or antigen-binding fragment thereof binds to glycoprotein G of RABV, for example, binds to antigenic site I or antigenic site III (or binds to an epitope that at least partially overlaps with antigenic site III) of glycoprotein G of RABV. Antigenic sites I and III of glycoprotein G of RABV are well known and described in the art (e.g., Buthelezi SG, Dirr HW, Chakauya E, Chikwamba R, Martens L, Tsekoa TL, Stoychev SH, Vandermarliere E. The Lyssavirus glycoprotein: A key to cross-immunity. Virology. 2016 Nov; 498: 250-256. doi: 10.1016 / j.virol.2016.08.034).

[0528] Interestingly, human anti-rabies antibodies most often recognize antigenic sites I or III on glycoprotein G of RABV, whereas, for example, mouse anti-rabies antibodies most often recognize antigenic site II on glycoprotein G of RABV. It is believed that the immunogenicity advantage of antigenic site II is lower in humans than in mice (Kramer RA, Marissen WE, Goudsmit J, Visser TJ, Clijsters-Van der Horst M, Bakker AQ, de Jong M, Jongeneelen M, Thijsse S, Backus HH, Rice AB, Weldon WC, Rupprecht CE, Dietzschold B, Bakker AB, de Kruif J (2005) The human antibody repertoire specific for rabies virus glycoprotein as selected from immune libraries. Eur J Immunol. 35(7):2131-45). Therefore, antibodies that recognize antigenic sites I and III on glycoprotein G of RABV are thought to be more effective in humans than antibodies that recognize antigenic site II on glycoprotein G of RABV.

[0529] Examples of antibodies that bind to antigenic sites I and III (or to an epitope that at least partially overlaps with antigenic site III) on the glycoprotein G of RABV are well known in the art. For example, two anti-RABV antibodies, CR57 and CR4098, were previously shown to recognize RABV G protein antigenic sites I and III, respectively (Bakker, ABH et al., J Virol 79, 9062–9068, 2005). In addition, WO 201 6 / 078761 describes a group of broadly neutralizing human anti-rabies virus antibodies, including antibodies RVA125, RVC3, RVC20, and RVD74 that bind to antigenic site I, and antibodies RVA122, RVA144, RVB492, RVC4, RVC69, RVC38, and RVC58 that bind to antigenic site III.

[0530] For example, antibody or its antigen binding fragment is given in combination with other anti-rabies virus antibody or its antigen binding fragment, for example as described herein.It should be understood that the two anti-rabies virus antibodies or its antigen binding fragment given in combination are different.For example, the two anti-rabies virus antibodies or its antigen binding fragment given in combination can specifically bind to the different epitopes of rabies virus glycoprotein G, specifically on the glycoprotein G of RABV. Targeting different epitopes (different antigenic sites) can avoid the occurrence of resistant virus strains and prevent the resistance variants (virus escape mutants) of the virus from escaping. Therefore, the combination of two anti-rabies virus antibodies that are bound to the different epitopes of the rabies virus G protein represents a treatment with unprecedented reactivity width and the escape mutant selection with reduced risk. Specifically, the combination of two or more monoclonal antibodies that are bound to different epitopes or sites on the rabies virus (for example, RABV) G protein improves protection and prevents the escape of the resistance variants of the virus. One skilled in the art can readily determine whether two or more antibodies bind to the same or different epitopes on the lyssavirus G protein, for example by using any competition study, such as described in Example 3 of WO 2016 / 078761, which is incorporated herein by reference.

[0531] One of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination can specifically bind to antigenic site I of glycoprotein G of rabies virus (e.g., RABV), and the other of the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination can specifically bind to antigenic site III (or to an epitope that at least partially overlaps with antigenic site III) of glycoprotein G of rabies virus (e.g., RABV).

[0532] The two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination can be contained in the same or different pharmaceutical compositions. In other words, the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination can be administered separately, for example in separate pharmaceutical compositions, or can be administered together, for example in the same pharmaceutical composition, i.e., as an antibody "cocktail". For example, the two anti-rabies virus antibodies or antigen-binding fragments thereof administered in combination are contained in the same pharmaceutical composition.

[0533] For example, an antibody or antigen-binding fragment thereof for use according to the invention as described herein and another antibody administered in combination are administered in equimolar amounts. If they are contained in the same pharmaceutical composition, (at least) both antibodies are particularly present (in the pharmaceutical composition) in equimolar amounts (e.g. as an equimolar mixture).

[0534] For example, an antibody or antigen-binding fragment thereof with an IC value of less than 10,000 ng / ml 50 Neutralizes at least 50% of lyssavirus infection of (i) RABV and (ii) a non-RABV lyssavirus selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, ARAV, LBV, MOK, SHIV, BBLV, WCBV, and IKOV. In other words, 50% neutralization (IC 50 The concentration of the antibody or antigen-binding fragment thereof required to bind to at least 50% of the above non-RABV lyssaviruses is, for example, less than 10,000 ng / ml.

[0535] Therefore, the antibodies according to the present invention have a particularly high or strong affinity for RABV and non-RABV lyssaviruses and are therefore particularly suitable for counteracting and / or at least partially preventing (reducing the occurrence of) RABV lyssavirus infection and / or non-RABV lyssavirus infection, and / or the side effects of RABV lyssavirus infection and / or non-RABV lyssavirus infection. In particular, IC 50 Antibodies with values ​​greater than 10,000 ng / ml are unlikely to be effective in vivo.

[0536] “At least 50% of non-RABV lyssaviruses selected from the group consisting of DUVV, EBLV-1, EBLV-2, ABLV, IRKV, KHUV, ARAV, LBV, MOK, SHIV, BBLV, WCBV, and IKOV” refers to at least 50% of the following species: Duvenhei virus (DUVV), European bat lyssavirus type 1 (EBLV-1) and type 2 (EBLV-2), Australian bat lyssavirus (ABLV), Irkut virus (IRKV), Kujand virus (KHUV), Aravan virus (ARAV), Lagos bat virus (LBV), Mokola virus (MOKV), Shimoni bat virus (SHIBV), Boklo bat lyssavirus (BBLV), West Caucasian bat virus (WCBV) and Ikoma lyssavirus (IKOV), i.e., at least 7 of the above 13 species.

[0537] Each individual lyssavirus species is considered to have an IC value below 10,000 ng / ml. 50 is neutralized whenever at least one isolate of ...

Claims

1. An anti-rabies virus antibody or an antigen-binding fragment thereof for use in treating rabies virus infection, wherein the antibody or the antigen-binding fragment thereof (i) administered into the central nervous system (CNS); and (ii) is given peripherally.

2. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 1, wherein the antibody or antigen-binding fragment thereof is first administered at least five days after exposure to rabies virus.

3. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 1, wherein the antibody or antigen-binding fragment thereof is first administered at least six days after exposure to rabies virus.

4. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 1, wherein the antibody or antigen-binding fragment thereof is first administered at least seven days after exposure to rabies virus.

5. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to claim 1, wherein the antibody or antigen-binding fragment thereof is first administered at least eight days after exposure to rabies virus.

6. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of claims 1 to 5, wherein the antibody or antigen-binding fragment thereof is first administered after the onset of symptoms of rabies virus infection.

7. The anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of claims 1 to 6, wherein peripheral administration of the antibody or antigen-binding fragment thereof and administration of the antibody or antigen-binding fragment thereof into the CNS are performed at approximately the same time.

8. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of claims 1 to 7, wherein the antibody or antigen-binding fragment thereof is administered peripherally and at the same time the antibody or antigen-binding fragment thereof is administered into the CNS.

9. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of claims 1 to 8, wherein the first peripheral administration of the antibody or antigen-binding fragment thereof and the first administration of the antibody or antigen-binding fragment thereof into the CNS occur on the same day.

10. An anti-rabies virus antibody or antigen-binding fragment thereof for use according to any one of claims 1 to 9, comprising a single peripheral administration of the antibody or antigen-binding fragment thereof.

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