( 2 (51) International Patent Classification: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, A61K 39/42 (2006.01) C07K 16/10 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, C07K 16/08 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US20 19/033 995 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 24 May 2019 (24.05.2019) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available) . ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 62/676,045 24 May 2018 (24.05.2018) US EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: LANKENAU INSTITUTE FOR MEDICAL TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, RESEARCH [US/US]; 100 Lancaster Avenue, Wyn- KM, ML, MR, NE, SN, TD, TG). newood, PA 19096 (US). (72) Inventor: DESSAIN, Scott K.; 1370 Indian Creek Drive, Published: Wynnewood, PA 19096 (US). — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the (74) Agent: BAK, Mary E. et al. ; Howson & Howson LLP, 350 claims and to be republished in the event of receipt of Sentry Parkway, Building 620, Suite 210, Blue Bell, PA amendments (Rule 48.2(h)) 19422 (US). — with sequence listing part of description (Rule 5.2(a)) (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (54) Title: COMPOSITIONS COMPRISING ANTIBODIES TO RABIES VIRUS AND THE USES THEREOF (57) Abstract: Anti-rabies antibodies e ito e-bindin fra ments and com osi¬ are er¬ COMPOSITIONS COMPRISING ANTIBODIES TO RABIES VIRUS AND THE USES THEREOF INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED IN ELECTRONIC FORM Applicant hereby incorporates by reference the Sequence Listing material filed in electronic form herewith. This file is labeled "MLHl05PCT_20l90523_ SequenceListing_ST25.txt", prepared May 24, 2019 and is 36,864 bytes in size. BACKGROUND OF THE INVENTION Rabies, being a major zoonotic disease, significantly impacts global public health. It is invariably fatal once clinical signs are apparent. The majority of human rabies deaths occur in developing countries. According to the CDC, more than 55,000 people, mostly in Africa and Asia, die from rabies every year - a rate of one person every ten minutes. India alone reports more than 50% of the global rabies deaths. Despite evidence that control of dog rabies through programs of animal vaccination and elimination of stray dogs can reduce the incidence of human rabies, exposure to rabid dogs is still the cause of over 90% of human exposures to rabies and of over 99% of human deaths worldwide. Because vaccines to prevent human rabies have been available for more than 100 years, most deaths from rabies occur in countries with inadequate public health resources and limited access to preventive treatment. These countries also have few diagnostic facilities and almost no rabies surveillance. The cost of these rabies prevention programs prohibits their full implementation in much of the developing world, and in even the most prosperous countries the cost of an effective dog rabies control program is a drain on public health resources. The estimated annual expenditure for rabies prevention in the United States is over US$300 million, most of which is spent on dog vaccinations. An annual turnover of approximately 25% in the dog population necessitates revaccination of millions of animals each year, and reintroduction of rabies through transport of infected animals from outside a controlled area is always a possibility should control programs lapse. Cell culture rabies vaccines have become widely available in developing countries. Currently, rabies vaccines made from inactivated cell cultures include human diploid cell vaccine (Imovax Rabies) and Purified Chick Embryo Cell Vaccine (RabAvert) and are well tolerated. Although it is a vaccine-preventable disease, effective rabies prevention in humans for post-exposure cases (i.e., category III bites) can require the combined administration of both rabies immunoglobulin (RIG) and vaccine. In still other instances, passive immunization with human anti-rabies immunoglobulin is valuable particularly in children and adults who have weakened immune systems or may not be good candidates for routine vaccinations for other reasons. It can be used with people who haven’t been vaccinated against a disease to which they’ve been exposed. For example, the passive rabies immunization (rabies immune globulin) is commonly used after a certain type of wild animal bites a child. SUMMARY OF THE INVENTION In one aspect, a recombinant, synthetic or monoclonal human antibody of an IgG class that binds to a rabies virus epitope, or a fragment of said antibody that binds a rabies virus epitope, is provided. The antibody or fragment comprises in one aspect, a heavy chain variable domain sequence that is an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 11, 3, 5, 7, or 1 or an amino acid sequence at least 80% identical to SEQ ID NO: 9, 11, 3, 5, 7, or 1. In another aspect, the antibody or fragment comprises a light chain variable domain sequence that is an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 12, 4, 6, 8 or 2 or an amino acid sequence at least 80% identical to these sequences. In still another embodiment, truncations and/or modifications of these sequences SEQ ID NO: 1-12 are described. In still another aspect, the antibody or fragment comprises both heavy chain and light chain variable regions from among those SEQ ID Nos identified herein. In a further embodiment, the antibody comprises a heavy chain and light chain sequence of SEQ ID NOs: 9 and 10, referred to as antibody 8C5. In a further embodiment, the antibody comprises a heavy chain and light chain sequence of SEQ ID NOs: 11 and 12, referred to as antibody 10H5. In a further embodiment, the antibody comprises a heavy chain and light chain sequence of SEQ ID NOs: 3 and 4, referred to as antibody 4H3. In a further embodiment, the antibody comprises a heavy chain/light chain sequence of SEQ ID NOs: 5 and 6, referred to as antibody 7A2. In another embodiment, the antibody comprises a heavy chain and light chain sequence of SEQ ID NOs: 7 and 8, referred to as antibody 7E8. In a further embodiment, the antibody comprises a heavy chain and light chain sequence of SEQ ID NOs: 1 and 2, referred to as antibody 4C12. In another aspect, a pharmaceutical composition for the prevention or treatment of rabies infection is provided that comprises at least one antibody or epitope-binding fragment or modification thereof described herein and a pharmaceutically acceptable carrier. In another aspect, nucleic acid sequences encoding the antibody fragments, and constructs (e.g., vectors or plasmids) containing the coding sequences, as well as compositions containing the nucleic acid sequences, vectors, or plasmids are also provided. In another aspect, a method for preventing rabies infection in an uninfected subject comprises administering an effective amount of a single antibody or epitope binding fragment or modification thereof as described herein. In another aspect, a method for preventing rabies infection in an uninfected subject comprises administering an effective amount of a mixture of antibodies or fragments described herein. In another aspect, a method for preventing rabies infection in a subject suspected of having rabies infection comprises administering an effective amount of a single antibody or epitope binding fragment or modification thereof as described herein. In another aspect, a method for preventing rabies infection in a subject suspected of having rabies infection comprises administering an effective amount of a mixture of antibodies or fragments described herein. In another aspect, a method for treating a subject infected with rabies virus comprises administering an effective amount of a single antibody or epitope binding fragment or modification thereof. In another aspect, a method for treating a subject infected with rabies virus comprises administering an effective amount of a mixture of antibodies or fragments as described herein. Methods of generating the antibodies, using the nucleic acid sequences and formulating the pharmaceutical compositions are also provided. Other aspects and advantages of these methods and compositions are described further in the following detailed description. BRIEF DESCRIPTION OF THE FIGURES FIGs. 1A, 1B and 1C identify the heavy and light chain amino acid sequences of anti-rabies antibodies 4C12, 4H3, 7A2, 7E8, 8C5 and 10H5 with accompanying SEQ ID Nos and with the CDR sequences highlighted in each sequence. The symbols used in the figures are: HC = heavy chain; LLC = lambda light chain; KLC = kappa light chain; numbers in brackets denote the sequence length. FIGs. 2A, 2B, 2C and 2D provide the nucleotide sequences encoding the heavy and light chains of anti-rabies antibodies 4C12, 4H3, 7A2, 7E8, 8C5 and 10H5 with accompanying SEQ ID NOs and with the CDR-encoding sequences highlighted in each sequence.