Method for treating hemophilia b

Abstract

The present invention relates to the field of medicine, in particular to a method for treating hemophilia B, comprising administering a recombinant viral vector AAV5-FIX in predetermined doses, as well as to use of the recombinant viral vector AAV5-FIX in predetermined doses.

Description

[0001]METHOD FOR TREATING HEMOPHILIA B. Field of the invention. The present invention relates to the field of medicine, in particular to a method for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at predetermined doses, as well as to use of the recombinant viral vector AAV5-FIX at predetermined doses. Background of the invention. Hemophilia B is a hereditary disease of the blood coagulation system involving a deficiency in coagulation factor IX (FIX) and caused by a mutation in the gene encoding FIX (Xq27). The disease is inherited in an X-linked recessive manner, however in some cases sporadic mutations are possible. The overall prevalence rate of hemophilia is 1:10,000 cases, 15-20% of which are hemophilia B (Schramm W. The history of haemophilia - a short review. Thromb Res.2014;134 Suppl 1:S4-9. doi: 10.1016 / j.thromres.2013.10.020). The prevalence rate of hemophilia B is 5:100,000 males, whereas severe hemophilia B occurs in 1.5:100000 males (Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Ann Intern Med. 2019;171(8):540-6. doi: 10.7326 / m19-1208). The disease debuts in childhood. The vast majority of patients are males. Rare cases of clinical manifestations have been described in women provided they inherited mutant alleles from both parents, as a result of a combination of mutation and inactivation of the other chromosome, as well as in some carrier females (Prevention CfDCa. What is Hemophilia? Centers for Disease Control and Prevention. U.S. Department of Health and Human Services. Bertamino M, Riccardi F, Banov L, Svahn J, Molinari AC. Hemophilia Care in the Pediatric Age. J Clin Med.2017;6(5). doi: 10.3390 / jcm6050054). Mostly, FIX activity and the severity of symptoms are in a direct relationship, but in some cases the laboratory phenotype and clinical phenotype of the disease may not overlap. Currently, the mainstay of treatment for patients with hemophilia B is replacement therapy with FIX concentrates, which are used both for prophylactic therapy and for the treatment of ongoing bleeding. Local hemostatic agents and fibrinolysis inhibitors can be used as additional therapy. Current treatment options for hemophilia B have a number of disadvantages. Replacement therapy with FIX concentrates has markedly improved the condition of patients, but at the same time has led to a large number of infections with human immunodeficiency viruses, hepatitis B and C. Today, medicinal products of this class undergo mandatory purification; this has virtually eliminated the risk of transmitting viral diseases, but the problem of inhibitors, i.e. antibodies that neutralize FIX activity, remains unresolved (Blanchette VS, Key NS, Ljung LR, Manco-Johnson MJ, van den Berg HM, Srivastava A. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost.2014;12(11):1935-9. doi: 10.1111 / jth.12672). Furthermore, FIX concentrates have a short half-life, require frequent administrations and periodic dose modifications, and, in some cases, the placement of a central venous catheter whose use can cause thrombotic complications and catheter- related infections (Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-44. doi: 10.1056 / NEJMoa067659). A significant proportion of patients receiving FIX concentrates continue to experience spontaneous bleeding (Oldenburg J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood.2015;125(13):2038-44. doi: 10.1182 / blood-2015-01-528414). RNA interference agents and monoclonal antibodies to tissue factor pathway inhibitor (TFPI) are at various stages of clinical development, but even if the studies are completed successfully, these medicinal products will require regular administration, which may be difficult for patients with severe chronic disease (Fassel H, McGuinn C. Haemophilia: factoring in new therapies. Br J Haematol. 2021;194(5):835-50. doi: 10.1111 / bjh.17580). Hemophilia appears to be an optimal target for gene therapy due to the large therapeutic range and the lack of need for strict expression control: the range of normal FIX levels is wide, 50–150%. It is expected that a single administration of the gene therapy product will provide FIX elevation to levels sufficient to minimize or completely eliminate clinical manifestations. There are positive data from long-term follow-up (up to 8 years) of patients treated with various gene therapy products which are currently at different stages of clinical development: to date, patients continue to maintain near- normal FIX levels (Arruda VR, Doshi BS. Gene Therapy for Hemophilia: Facts and Quandaries in the 21st Century. Mediterr J Hematol Infect Dis. 2020;12(1):e2020069. doi: 10.4084 / mjhid.2020.069). Thus, there is an actual need to develop a method for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at predetermined doses, as well as the use of the recombinant viral vector AAV5-FIX at predetermined doses for treating hemophilia B. Description of the invention. The terms used in the description of this invention appear below. The term "pharmaceutical composition" refers to a composition and / or formulation comprising a vector based on recombinant adeno-associated virus AAV5 in a therapeutically effective amount and excipients or auxiliary substances (carriers, diluents, fillers, solvents, and the like), the choice and proportions of which depend on the type and route of administration and dosage. A pharmaceutical composition is "stable" if the active agent retains physical stability and / or chemical stability and / or biological activity thereof during the specified shelf life at a storage temperature. Further, the active agent may retain both physical and chemical stability, as well as biological activity. Storage period is adjusted based on the results of stability test in accelerated or natural aging conditions. The term "buffer" or "buffer solution" refers to an aqueous solution comprising a mixture of an acid (typically a weak acid, such as e.g. acetic acid, citric acid) and a conjugated base thereof (such as e.g. an acetate or citrate salt, e.g. sodium acetate, sodium citrate, as well as hydrates of said salts, e.g. sodium acetate trihydrate) or alternatively a mixture of a base (typically a weak base, e.g. histidine) and a conjugated acid thereof (e.g. histidine hydrochloride or histidine hydrochloride monohydrate or L-histidine hydrochloride (h / c) monohydrate (m / h) or L-histidine h / c m / h or histidine h / c m / h). The pH value of a "buffer solution" changes only slightly upon addition thereto of a small quantity of strong base or strong acid, as well as upon dilution or concentration due to the "buffering effect" imparted by a "buffering agent". Amino acids are L-amino acids. For example, if histidine and histidine hydrochloride monohydrate are used, it is typically L-histidine and L-histidine hydrochloride monohydrate. For example, if arginine is used, it is typically L-arginine. Amino acid equivalents, for example, pharmaceutically acceptable proline salts (for example, proline hydrochloride) may also be used. Premedication is the preliminary medicinal preparation of a patient (subject) for procedures or product infusion. Postmedication is the process of providing medical care and medicinal support after a procedure or product infusion. Concomitant therapy is therapy that is administered further to therapy with the ANB-002 product and includes a glucocorticoid, FIX (blood coagulation factor) concentrate and / or an immunosuppressive agent. The term "doses" refers to the recommended dose of the product of the present invention, or of the ANB-002 product, or of a glucocorticoid. The term "target dose" refers to the full dose of the product of the present invention, or the full dose of the ANB-002 product, or of the glucocorticoid prednisolone, or of other glucocorticoid of the present invention, or an available equivalent thereof. The term "dose reduction" means a gradual reduction in the target dose for the product of the present invention, or for a glucocorticoid product. Target dose reduction involves administering the drug for some time at half the target dose, and then administering at a quarter of the target dose. The term some time includes administration for 1, 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, or 30 days. The term "vector" as used herein means a nucleic acid molecule capable of transporting other nucleic acid to which it has been linked. The terms "nucleic acid", "nucleic sequence" or "nucleic acid sequence", "polynucleotide", "oligonucleotide", "polynucleotide sequence" and "nucleotide sequence", used interchangeably in the present invention, mean a precise sequence of nucleotides, modified or not, determining a fragment or a region of a nucleic acid, containing unnatural nucleotides or not, and being either a double-strand DNA or RNA, a single-strand DNA or RNA, or transcription products of said DNAs. The recombinant viral vector AAV5-FIX or recombinant adeno-associated virus serotype 5 expressing human coagulation factor IX refers to a nucleic acid and regulatory elements that are incorporated within the AAV capsid, may also be provided in the form a pharmaceutical composition with any excipients or in the form of the ANB-002 product. The term "use" refers to the suitability for use of the recombinant viral vector AAV5-FIX according to the invention or a pharmaceutical composition comprising same for treating hemophilia B, alleviating the course of diseases or disorders, improving quality of life, preventing complications. The term "method for treating" refers to the suitability for use of the recombinant viral vector AAV5-FIX according to the invention or a pharmaceutical composition comprising same for treating hemophilia B, alleviating the course of diseases, improving quality of life, accelerating remission. "Treat" or "treatment" of a disease, disorder or condition may comprise the prevention or delay of the onset of clinical symptoms of a disease, disorder or condition developing in human, the inhibition of a disease, disorder or condition, i.e. stop, reduction or delay of the development of a disease or a relapse thereof (in case of maintenance therapy) or at least one clinical or subclinical symptom thereof, or the alleviation or easement of a disease, i.e. the causing of regression of a disease, disorder or condition. As used herein, to "alleviate" a disease, disorder or condition means reducing the severity and / or occurrence frequency of the symptoms of the disease, disorder, or condition. SEQ ID NO: 1 refers to the nucleotide sequence of the gene encoding Factor IX (FIX). SEQ ID NO: 2 refers to the complete nucleotide sequence that includes the nucleotide sequence of the gene encoding Factor IX (FIX) with SEQ ID NO: 1, and regulatory elements. SEQ ID NO: 2 includes the following elements in the 5'-end to 3'-end direction: a left-hand (first) ITR (inverted terminal repeats); TTR promoter (transthyretin promoter); an intron of the hBG1 gene (an intron-bearing fragment of the human β-globin gene); a nucleic acid encoding the FIX (blood coagulation factor IX) protein with the nucleotide sequence of SEQ ID NO: 1; an hGH1 polyadenylation signal (human growth hormone gene polyadenylation signal); a right-hand (second) ITR. SEQ ID NO: 3 refers to the amino acid sequence of the protein VP1 comprised in the capsid of the AAV5-based recombinant virus. SEQ ID NO: 4 refers to the amino acid sequence of the protein VP2 comprised in the capsid of the AAV5-based recombinant virus. SEQ ID NO: 5 refers to the amino acid sequence of the protein VP3 comprised in the capsid of the AAV5-based recombinant virus. The present invention discloses methods for treating hemophilia B comprising administering the recombinant viral vector AAV5-FIX using predetermined doses. In one embodiment, the present invention relates to methods of treating hemophilia B in a subject comprising administering the recombinant viral vector AAV5-FIX using predetermined doses. The following doses are calculated based on the patient's body weight. In one embodiment, the present invention relates to methods for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to methods for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to methods for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to methods for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to methods for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1013vg / kg. In one embodiment, the present invention relates to methods for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1013vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg, or 1.0 × 1012vg / kg to 9.9 × 1013vg / kg, 1.0 × 1012vg / kg to 9.8 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.7 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.6 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.5 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.4 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.3 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.2 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.1 × 1013vg / kg., or 1.0 × 1012vg / kg to 9.0 × 1013vg / kg., or 1.1 × 1012vg / kg to 8.9 × 1013vg / kg, or 1.2 × 1012vg / kg to 8.8 × 1013vg / kg., or 1.3 × 1012vg / kg to 8.7 × 1013vg / kg., or 1.4 × 1012vg / kg to 8.6 × 1013vg / kg., or 1.5 × 1012vg / kg to 8.5 × 1013vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg to 2.0 × 1012vg / kg, or 2.0 × 1012vg / kg to 3.0 × 1012vg / kg, or 2.3 × 1012vg / kg to 2.8 × 1012vg / kg, or 2.4 × 1012vg / kg to 2.6 × 1012vg / kg, or 3.0 × 1012vg / kg to 4.0 × 1012vg / kg, or 4.0 × 1012vg / kg to 5.0 × 1012vg / kg, or 4.5 × 1012vg / kg to 5.5 × 1012vg / kg, or 4.8 × 1012vg / kg to 5.3 × 1012vg / kg, or 4.9 × 1012vg / kg to 5.1 × 1012vg / kg, or 5.0 × 1012vg / kg to 6.0 × 1012vg / kg, or 6.0 × 1012vg / kg to 7.0 × 1012vg / kg, or 7.0 × 1012vg / kg to 8.0 × 1012vg / kg, or 8.0 × 1012vg / kg to 9.0 × 1012vg / kg, or 9.0 × 1012vg / kg to 1.0 × 1013vg / kg, or 1.0 × 1013vg / kg to 2.0 × 1013vg / kg, or 1.5 × 1013vg / kg to 2.5 × 1013vg / kg, or 1.8 × 1013vg / kg to 2.3 × 1013vg / kg, or 1.9 × 1013vg / kg to 2.1 × 1013vg / kg, or 2.0 × 1013vg / kg to 3.0 × 1013vg / kg, or 3.0 × 1013vg / kg to 4.0 × 1013vg / kg, or 4.0 × 1013vg / kg to 5.0 × 1013vg / kg, or 4.5 × 1013vg / kg to 5.5 × 1013vg / kg, or 4.8 × 1013vg / kg to 5.3 × 1013vg / kg, 1013vg / kg, or 4.9 × 1013vg / kg to 5.1 × 1013vg / kg, or 5.0 × 1013vg / kg to 6.0 × 1013vg / kg, or 6.0 × 1013vg / kg to 7.0 × 1013vg / kg, or 7.0 × 1013vg / kg to 8.0 × 1013vg / kg, or 8.0 × 1013vg / kg to 9.0 × 1013vg / kg, or 9.0 × 1013vg / kg to 1.0 × 1014vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg, or 1.1 × 1012vg / kg, or 1.2 × 1012vg / kg, or 1.3 × 1012vg / kg, or 1.4 × 1012vg / kg, or 1.5 × 1012vg / kg, or 1.6 × 1012vg / kg, or 1.7 × 1012vg / kg, or 1.8 × 1012vg / kg, or 1.9 × 1012vg / kg, or 2.0 × 1012vg / kg, or 2.1 × 1012vg / kg, or 2.2 × 1012vg / kg, or 2.3 × 1012vg / kg, or 2.4 × 1012vg / kg, or 2.5 × 1012vg / kg, or 2.6 × 1012vg / kg, or 2.7 × 1012vg / kg, or 2.8 × 1012vg / kg, or 2.9 × 1012vg / kg, or 3.0 × 1012vg / kg, or 3.1 × 1012vg / kg, or 3.2 × 1012vg / kg, or 3.3 × 1012vg / kg, or 3.4 × 1012vg / kg, or 3.5 × 1012vg / kg, or 3.6 × 1012vg / kg, or 3.7 × 1012vg / kg, or 3.8 × 1012vg / kg, or 3.9 × 1012vg / kg, or 4.0 × 1012vg / kg, or 4.1 × 1012vg / kg, or 4.2 × 1012vg / kg, or 4.3 × 1012vg / kg, or 4.4 × 1012vg / kg, or 4.5 × 1012vg / kg, or 4.6 × 1012vg / kg, or 4.7 × 1012vg / kg, or 4.8 × 1012vg / kg, or 4.9 × 1012vg / kg, or 5.0 × 1012vg / kg, or 5.1 × 1012vg / kg, or 5.2 × 1012vg / kg, or 5.3 × 1012vg / kg, or 5.4 × 1012vg / kg, or 5.5 × 1012vg / kg, or 5.6 × 1012vg / kg, or 5.7 × 1012vg / kg, or 5.8 × 1012vg / kg, or 5.9 × 1012vg / kg, or 6.0 × 1012vg / kg, or 6.1 × 1012vg / kg, or 6.2 × 1012vg / kg, or 6.3 × 1012vg / kg, or 6.4 × 1012vg / kg, or 6.5 × 1012vg / kg, or 6.6 × 1012vg / kg, or 6.7 × 1012vg / kg, or 6.8 × 1012vg / kg, or 6.9 × 1012vg / kg, or 7.0 × 1012vg / kg, or 7.1 × 1012vg / kg, or 7.2 × 1012vg / kg, or 7.3 × 1012vg / kg, or 7.4 × 1012vg / kg, or 7.5 × 1012vg / kg, or 7.6 × 1012vg / kg, or 7.7 × 1012vg / kg, or 7.8 × 1012vg / kg, or 7.9 × 1012vg / kg, or 8.0 × 1012vg / kg, or 8.1 × 1012vg / kg, or 8.2 × 1012vg / kg, or 8.3 × 1012vg / kg, or 8.4 × 1012vg / kg, or 8.5 × 1012vg / kg, or 8.6 × 1012vg / kg, or 8.7 × 1012vg / kg, or 8.8 × 1012vg / kg, or 8.9 × 1012vg / kg, or 9.0 × 1012vg / kg, or 9.1 × 1012vg / kg, or 9.2 × 1012vg / kg, or 9.3 × 1012vg / kg, or 9.4 × 1012vg / kg, or 9.5 × 1012vg / kg, or 9.6 × 1012vg / kg, or 9.7 × 1012vg / kg, or 9.8 × 1012vg / kg, or 9.9 × 1012vg / kg, or 1.0 × 1013vg / kg, or 1.1 × 1013vg / kg, or 1.2 × 1013vg / kg, or 1.3 × 1013vg / kg, or 1.4 × 1013vg / kg, or 1.5 × 1013vg / kg, or 1.6 × 1013vg / kg, or 1.7 × 1013vg / kg, or 1.8 × 1013vg / kg, or 1.9 × 1013vg / kg, or 2.0 × 1013vg / kg, or 2.1 × 1013vg / kg, or 2.2 × 1013vg / kg, or 2.3 × 1013vg / kg, or 2.4 × 1013vg / kg, or 2.5 × 1013vg / kg, or 2.6 × 1013vg / kg, or 2.7 × 1013vg / kg, or 2.8 × 1013vg / kg, or 2.9 × 1013vg / kg, or 3.0 × 1013vg / kg, or 3.1 × 1013vg / kg, or 3.2 × 1013vg / kg, or 3.3 × 1013vg / kg, or 3.4 × 1013vg / kg, or 3.5 × 1013vg / kg, or 3.6 × 1013vg / kg, or 3.7 × 1013vg / kg, or 3.8 × 1013vg / kg, or 3.9 × 1013vg / kg, or 4.0 × 1013vg / kg, or 4.1 × 1013vg / kg, or 4.2 × 1013vg / kg, or 4.3 × 1013vg / kg, or 4.4 × 1013vg / kg, or 4.5 × 1013vg / kg, or 4.6 × 1013vg / kg, or 4.7 × 1013vg / kg, or 4.8 × 1013vg / kg, or 4.9 × 1013vg / kg, or 5.0 × 1013vg / kg, or 5.1 × 1013vg / kg, or 5.2 × 1013vg / kg, or 5.3 × 1013vg / kg, or 5.4 × 1013vg / kg, or 5.5 × 1013vg / kg, or 5.6 × 1013vg / kg, or 5.7 × 1013vg / kg, or 5.8 × 1013vg / kg, or 5.9 × 1013vg / kg, or 6.0 × 1013vg / kg, or 6.1 × 1013vg / kg, or 6.2 × 1013vg / kg, or 6.3 × 1013vg / kg, or 6.4 × 1013vg / kg, or 6.5 × 1013vg / kg, or 6.6 × 1013vg / kg, or 6.7 × 1013vg / kg, or 6.8 × 1013vg / kg, or 6.9 × 1013vg / kg, or 7.0 × 1013vg / kg, or 7.1 × 1013vg / kg, or 7.2 × 1013vg / kg, or 7.3 × 1013vg / kg, or 7.4 × 1013vg / kg, or 7.5 × 1013vg / kg, or 7.6 × 1013vg / kg, or 7.7 × 1013vg / kg, or 7.8 × 1013vg / kg, or 7.9 × 1013vg / kg, or 8.0 × 1013vg / kg, or 8.1 × 1013vg / kg, or 8.2 × 1013vg / kg, or 8.3 × 1013vg / kg, or 8.4 × 1013vg / kg, or 8.5 × 1013vg / kg, or 8.6 × 1013vg / kg, or 8.7 × 1013vg / kg, or 8.8 × 1013vg / kg, or 8.9 × 1013vg / kg, or 9.0 × 1013vg / kg, or 9.1 × 1013vg / kg, or 9.2 × 1013vg / kg, or 9.3 × 1013vg / kg, or 9.4 × 1013vg / kg, or 9.5 × 1013vg / kg, or 9.6 × 1013vg / kg, or 9.7 × 1013vg / kg, or 9.8 × 1013vg / kg, or 9.9 × 1013vg / kg, or 1.0 × 1014vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, one or more buffers, one or more amino acids, one or more inorganic salts, one or more surfactants, and one or more solvents. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine, arginine, sodium chloride, magnesium chloride, a surfactant, and water. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248-0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15-0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX in an amount of 1.5 x 1012– 2.5 x 1013vg, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248- 0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15-0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; arginine – 0.348 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; L- arginine – 0.348 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; L- arginine – 0.35 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.348 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; L-arginine – 0.348 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; L-arginine – 0.35 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the pharmaceutical composition is present in vials. In some embodiments, the pharmaceutical composition is present in vials with a filling volume of 1-25 ml, or 1-20 ml, or 1-12 ml, or 1-10 ml, or 1-8 ml, or 1-6 ml, or 1-5 ml. In some embodiments, the pharmaceutical composition is present in vials with a filling volume of 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, or 20 ml. In some embodiments, hemophilia B is mild hemophilia B, or moderate hemophilia B, or severe hemophilia B. In some embodiments, hemophilia B is: (i) severe hemophilia B with FIX activity < 1 %; (ii) severe hemophilia B with FIX activity <1 IU / dl; (iii) moderate hemophilia B with FIX activity of 1-5 %; (iv) moderate hemophilia B with FIX activity of 1-5 IU / dl; (v) mild hemophilia B with FIX activity > 5%; (vi) mild hemophilia B with FIX activity of 5-40 IU / dl; (vii) hemophilia B without FIX inhibitor (inhibitor titer <0.6 BU); (viii) hemophilia B with FIX inhibitor (inhibitor titer ≥0.6 BU); (ix) hemophilia B with antibodies to AAV5; (x) hemophilia B with antibodies to AAV5 (antibody to AAV5 titer > 1:5); (xi) hemophilia B without antibodies to AAV5; or (xii) hemophilia B without antibodies to AAV5 (antibody to AAV5 titer < 1:5); In some embodiments, the recombinant virus of the vector AAV5-FIX comprises: 1) a nucleic acid that includes a nucleic acid with the nucleotide sequence of SEQ ID NO: 1 encoding the FIX (blood coagulation factor IX) protein; and 2) a capsid of the recombinant adeno-associated virus serotype 5. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 having the amino acid sequence of SEQ ID NO: 3. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises AAV5 proteins VP1, VP2, and VP3. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO: 5. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises proteins VP1 with the amino acid sequence of SEQ ID NO: 3 with one or more point mutations, VP2 with the amino acid sequence of SEQ ID NO: 4 with one or more point mutations, and VP3 with the amino acid sequence of SEQ ID NO: 5 with one or more point mutations. In some embodiments, the nucleic acid includes the following elements in the 5'-end to 3'-end direction: a left-hand (first) ITR (inverted terminal repeats); TTR promoter (transthyretin promoter); an intron of the hBG1 gene (an intron-bearing fragment of the human β-globin gene); a nucleic acid encoding the FIX (blood coagulation factor IX) protein with the nucleotide sequence of SEQ ID NO: 1; an hGH1 polyadenylation signal (human growth hormone gene polyadenylation signal); a right-hand (second) ITR. In some embodiments, the nucleic acid is represented by the nucleotide sequence of SEQ ID NO: 2. In some embodiments, the recombinant viral vector AAV5-FIX comprises: 1) a nucleic acid represented by the nucleotide sequence of SEQ ID NO: 2; 2) the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO: 5. In some embodiments, the administration of the recombinant viral vector AAV5-FIX is carried out by way of a single administration. In some embodiments, the administration of the recombinant viral vector AAV5-FIX is carried out by way of a single intravenous administration. In some embodiments, further comprises premedication, postmedication, and / or concomitant therapy. In some embodiments, further comprises premedication, postmedication, and / or concomitant therapy in a subject. In some embodiments, further comprises premedication, postmedication and / or concomitant therapy using glucocorticoid products. In some embodiments, further comprises premedication, postmedication and / or concomitant therapy using an immunosuppressive agent and / or a human coagulation factor IX product.https: / / www.vidal.ru / drugs / molecule / 2117 In some embodiments, the immunosuppressive agent is selected from a glucocorticoid, an antimetabolite, an alkylating agent, a cytostatic, a calcineurin inhibitor, an mTOR inhibitor, a monoclonal antibody, or other immunosuppressant. In some embodiments, further comprises concomitant therapy using human coagulation factor IX In some embodiments, further comprises the administration of glucocorticoids. In some embodiments, premedication, postmedication, and / or concomitant therapy are administered: (i) daily prior to administration of the recombinant viral vector AAV5-FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy are administered: (i) daily 1,2,3,4,5,6,7,8,9 or 10 days prior to administration of the recombinant viral vector AAV5- FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered one day prior to the administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered 24 hours (+ / - 60 minutes) prior to the administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered on the day of administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered daily post administration of the recombinant viral vector AAV5-FIX in targeted, reduced, or pulse therapy. In some embodiments, premedication, postmedication and / or concomitant therapy is administered one day prior to administration of the recombinant viral vector AAV5-FIX, and daily post administration of the recombinant viral vector AAV5-FIX, including the day of administration. In some embodiments, premedication, postmedication and / or concomitant therapy is administered one day prior to administration of the recombinant viral vector AAV5-FIX, and daily post administration of the recombinant viral vector AAV5-FIX for 60 days, including the day of administration. In some embodiments, the glucocorticoid is selected from prednisolone, prednisone, hydrocortisone, cortisone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, fludrocortisone, fluticasone, mazipredone, or an available equivalent. In some embodiments, prednisolone is selected at a dose of 0.10-30 mg / kg / day; or 0.10-25 mg / kg / day; or 0.10-20 mg / kg / day; or 0.10-19 mg / kg / day; or 0.10-18 mg / kg / day; or 0.10-17 mg / kg / day; or 0.10-16 mg / kg / day; or 0.10-15 mg / kg / day; or 0.10-14 mg / kg / day; or 0.10-13 mg / kg / day; or 0.10-12 mg / kg / day; or 0.10-11 mg / kg / day; or 0.10-10 mg / kg / day; or 0.10-9 mg / kg / day; or 0.10-8 mg / kg / day; or 0.10-7 mg / kg / day; or 0.10-6 mg / kg / day; or 0.10-5 mg / kg / day; or 0.10-4 mg / kg / day; or 0.10-3 mg / kg / day; or 0.10-2 mg / kg / day; or 0.20-1.25 mg / kg / day; or 0.20-1.25 mg / kg / day; or 0.20-1.1 mg / kg / day; or 0.20-1.05 mg / kg / day; or 0.25-1.00 mg / kg / day. In some embodiments, prednisolone is administered at a dose of 0.10 mg / kg / day; or 0.15 mg / kg / day; or 0.20 mg / kg / day; or 0.25 mg / kg / day; or 0.30 mg / kg / day; or 0.35 mg / kg / day; or 0.40 mg / kg / day; or 0.45 mg / kg / day; or 0.50 mg / kg / day; or 0.55 mg / kg / day; or 0.60 mg / kg / day; or 0.65 mg / kg / day; or 0.70 mg / kg / day; or 0.75 mg / kg / day; or 0.80 mg / kg / day; or 0.85 mg / kg / day; or 0.90 mg / kg / day; or 0.95 mg / kg / day; or 1 mg / kg / day; or 1.05 mg / kg / day; or 1.10 mg / kg / day; or 1.15 mg / kg / day; or 1.20 mg / kg / day; or 1.25 mg / kg / day; or 1.30 mg / kg / day; or 1.35 mg / kg / day; or 1.40 mg / kg / day; or 1.45 mg / kg / day; or 1.50 mg / kg / day; or 2.0 mg / kg / day; or 3.0 mg / kg / day; or 4.0 mg / kg / day; or 5.0 mg / kg / day; or 6.0 mg / kg / day; or 7.0 mg / kg / day; or 8.0 mg / kg / day; or 9.0 mg / kg / day; or 10.0 mg / kg / day; or 11.0 mg / kg / day; or 12.0 mg / kg / day; or 13.0 mg / kg / day; or 14.0 mg / kg / day; or 15.0 mg / kg / day; or 16.0 mg / kg / day; or 17.0 mg / kg / day; or 18.0 mg / kg / day; or 19.0 mg / kg / day; or 20.0 mg / kg / day; or 25.0 mg / kg / day; or 30.0 mg / kg / day. Other glucocorticoids may be used at doses equivalent to the above doses of prednisolone. The present invention discloses the use of a recombinant viral vector AAV5-FIX for the treatment of hemophilia B using predetermined doses. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B in a subject using predetermined doses. In some embodiments, the invention relates to the use of the recombinant viral vector AAV5- FIX in the manufacture of a medicament for treating hemophilia B using predetermined doses. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used for treating hemophilia B using predetermined doses. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used in the manufacture of a medicament for treating hemophilia B using predetermined doses. The following doses are calculated based on the patient's body weight. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B, comprising administering the recombinant viral vector AAV5- FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used for treating hemophilia B at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used in the manufacture of a medicament for treating hemophilia B at a dose of 1.0 × 1011vg / kg to 1.0 × 1015vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B, comprising administering the recombinant viral vector AAV5- FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used for treating hemophilia B at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used in the manufacture of a medicament for treating hemophilia B at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B, comprising administering the recombinant viral vector AAV5- FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In one embodiment, the present invention relates to the use of the recombinant viral vector AAV5-FIX in the manufacture of a medicament for treating hemophilia B in a subject, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used for treating hemophilia B at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In some embodiments, the invention relates to a recombinant viral vector AAV5-FIX used in the manufacture of a medicament for treating hemophilia B at a dose of 1.0 × 1012vg / kg to 9.0 × 1014vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg, or 1.0 × 1012vg / kg to 9.9 × 1013vg / kg, 1.0 × 1012vg / kg to 9.8 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.7 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.6 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.5 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.4 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.3 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.2 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.1 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.0 × 1013vg / kg, or 1.1 × 1012vg / kg to 8.9 × 1013vg / kg, or 1.2 × 1012vg / kg to 8.8 × 1013vg / kg, or 1.3 × 1012vg / kg to 8.7 × 1013vg / kg., or 1.4 × 1012vg / kg to 8.6 × 1013vg / kg, or 1.5 × 1012vg / kg to 8.5 × 1013vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg to 2.0 × 1012vg / kg, or 2.0 × 1012vg / kg to 3.0 × 1012vg / kg, or 2.3 × 1012vg / kg to 2.8 × 1012vg / kg, or 2.4 × 1012vg / kg to 2.6 × 1012vg / kg, or 3.0 × 1012vg / kg to 4.0 × 1012vg / kg, or 4.0 × 1012vg / kg to 5.0 × 1012vg / kg, or 4.5 × 1012vg / kg to 5.5 × 1012vg / kg, or 4.8 × 1012vg / kg to 5.3 × 1012vg / kg, or 4.9 × 1012vg / kg to 5.1 × 1012vg / kg, or 5.0 × 1012vg / kg to 6.0 × 1012vg / kg, or 6.0 × 1012vg / kg to 7.0 × 1012vg / kg, or 7.0 × 1012vg / kg to 8.0 × 1012vg / kg, or 8.0 × 1012vg / kg to 9.0 × 1012vg / kg, or 9.0 × 1012vg / kg to 1.0 × 1013vg / kg, or 1.0 × 1013vg / kg to 2.0 × 1013vg / kg, or 1.5 × 1013vg / kg to 2.5 × 1013vg / kg, or 1.8 × 1013vg / kg to 2.3 × 1013vg / kg, or 1.9 × 1013vg / kg to 2.1 × 1013vg / kg, or 2.0 × 1013vg / kg to 3.0 × 1013vg / kg, or 3.0 × 1013vg / kg to 4.0 × 1013vg / kg, or 4.0 × 1013vg / kg to 5.0 × 1013vg / kg, or 4.5 × 1013vg / kg to 5.5 × 1013vg / kg, or 4.8 × 1013vg / kg to 5.3 × 1013vg / kg, 1013vg / kg, or 4.9 × 1013vg / kg to 5.1 × 1013vg / kg, or 5.0 × 1013vg / kg to 6.0 × 1013vg / kg, or 6.0 × 1013vg / kg to 7.0 × 1013vg / kg, or 7.0 × 1013vg / kg to 8.0 × 1013vg / kg, or 8.0 × 1013vg / kg to 9.0 × 1013vg / kg, or 9.0 × 1013vg / kg to 1.0 × 1014vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered at a dose of 1.0 × 1012vg / kg, or 1.1 × 1012vg / kg, or 1.2 × 1012vg / kg, or 1.3 × 1012vg / kg, or 1.4 × 1012vg / kg, or 1.5 × 1012vg / kg, or 1.6 × 1012vg / kg, or 1.7 × 1012vg / kg, or 1.8 × 1012vg / kg, or 1.9 × 1012vg / kg, or 2.0 × 1012vg / kg, or 2.1 × 1012vg / kg, or 2.2 × 1012vg / kg, or 2.3 × 1012vg / kg, or 2.4 × 1012vg / kg, or 2.5 × 1012vg / kg, or 2.6 × 1012vg / kg, or 2.7 × 1012vg / kg, or 2.8 × 1012vg / kg, or 2.9 × 1012vg / kg, or 3.0 × 1012vg / kg, or 3.1 × 1012vg / kg, or 3.2 × 1012vg / kg, or 3.3 × 1012vg / kg, or 3.4 × 1012vg / kg, or 3.5 × 1012vg / kg, or 3.6 × 1012vg / kg, or 3.7 × 1012vg / kg, or 3.8 × 1012vg / kg, or 3.9 × 1012vg / kg, or 4.0 × 1012vg / kg, or 4.1 × 1012vg / kg, or 4.2 × 1012vg / kg, or 4.3 × 1012vg / kg, or 4.4 × 1012vg / kg, or 4.5 × 1012vg / kg, or 4.6 × 1012vg / kg, or 4.7 × 1012vg / kg, or 4.8 × 1012vg / kg, or 4.9 × 1012vg / kg, or 5.0 × 1012vg / kg, or 5.1 × 1012vg / kg, or 5.2 × 1012vg / kg, or 5.3 × 1012vg / kg, or 5.4 × 1012vg / kg, or 5.5 × 1012vg / kg, or 5.6 × 1012vg / kg, or 5.7 × 1012vg / kg, or 5.8 × 1012vg / kg, or 5.9 × 1012vg / kg, or 6.0 × 1012vg / kg, or 6.1 × 1012vg / kg, or 6.2 × 1012vg / kg, or 6.3 × 1012vg / kg, or 6.4 × 1012vg / kg, or 6.5 × 1012vg / kg, or 6.6 × 1012vg / kg, or 6.7 × 1012vg / kg, or 6.8 × 1012vg / kg, or 6.9 × 1012vg / kg, or 7.0 × 1012vg / kg, or 7.1 × 1012vg / kg, or 7.2 × 1012vg / kg, or 7.3 × 1012vg / kg, or 7.4 × 1012vg / kg, or 7.5 × 1012vg / kg, or 7.6 × 1012vg / kg, or 7.7 × 1012vg / kg, or 7.8 × 1012vg / kg, or 7.9 × 1012vg / kg, or 8.0 × 1012vg / kg, or 8.1 × 1012vg / kg, or 8.2 × 1012vg / kg, or 8.3 × 1012vg / kg, or 8.4 × 1012vg / kg, or 8.5 × 1012vg / kg, or 8.6 × 1012vg / kg, or 8.7 × 1012vg / kg, or 8.8 × 1012vg / kg, or 8.9 × 1012vg / kg, or 9.0 × 1012vg / kg, or 9.1 × 1012vg / kg, or 9.2 × 1012vg / kg, or 9.3 × 1012vg / kg, or 9.4 × 1012vg / kg, or 9.5 × 1012vg / kg, or 9.6 × 1012vg / kg, or 9.7 × 1012vg / kg, or 9.8 × 1012vg / kg, or 9.9 × 1012vg / kg, or 1.0 × 1013vg / kg, or 1.1 × 1013vg / kg, or 1.2 × 1013vg / kg, or 1.3 × 1013vg / kg, or 1.4 × 1013vg / kg, or 1.5 × 1013vg / kg, or 1.6 × 1013vg / kg, or 1.7 × 1013vg / kg, or 1.8 × 1013vg / kg, or 1.9 × 1013vg / kg, or 2.0 × 1013vg / kg, or 2.1 × 1013vg / kg, or 2.2 × 1013vg / kg, or 2.3 × 1013vg / kg, or 2.4 × 1013vg / kg, or 2.5 × 1013vg / kg, or 2.6 × 1013vg / kg, or 2.7 × 1013vg / kg, or 2.8 × 1013vg / kg, or 2.9 × 1013vg / kg, or 3.0 × 1013vg / kg, or 3.1 × 1013vg / kg, or 3.2 × 1013vg / kg, or 3.3 × 1013vg / kg, or 3.4 × 1013vg / kg, or 3.5 × 1013vg / kg, or 3.6 × 1013vg / kg, or 3.7 × 1013vg / kg, or 3.8 × 1013vg / kg, or 3.9 × 1013vg / kg, or 4.0 × 1013vg / kg, or 4.1 × 1013vg / kg, or 4.2 × 1013vg / kg, or 4.3 × 1013vg / kg, or 4.4 × 1013vg / kg, or 4.5 × 1013vg / kg, or 4.6 × 1013vg / kg, or 4.7 × 1013vg / kg, or 4.8 × 1013vg / kg, or 4.9 × 1013vg / kg, or 5.0 × 1013vg / kg, or 5.1 × 1013vg / kg, or 5.2 × 1013vg / kg, or 5.3 × 1013vg / kg, or 5.4 × 1013vg / kg, or 5.5 × 1013vg / kg, or 5.6 × 1013vg / kg, or 5.7 × 1013vg / kg, or 5.8 × 1013vg / kg, or 5.9 × 1013vg / kg, or 6.0 × 1013vg / kg, or 6.1 × 1013vg / kg, or 6.2 × 1013vg / kg, or 6.3 × 1013vg / kg, or 6.4 × 1013vg / kg, or 6.5 × 1013vg / kg, or 6.6 × 1013vg / kg, or 6.7 × 1013vg / kg, or 6.8 × 1013vg / kg, or 6.9 × 1013vg / kg, or 7.0 × 1013vg / kg, or 7.1 × 1013vg / kg, or 7.2 × 1013vg / kg, or 7.3 × 1013vg / kg, or 7.4 × 1013vg / kg, or 7.5 × 1013vg / kg, or 7.6 × 1013vg / kg, or 7.7 × 1013vg / kg, or 7.8 × 1013vg / kg, or 7.9 × 1013vg / kg, or 8.0 × 1013vg / kg, or 8.1 × 1013vg / kg, or 8.2 × 1013vg / kg, or 8.3 × 1013vg / kg, or 8.4 × 1013vg / kg, or 8.5 × 1013vg / kg, or 8.6 × 1013vg / kg, or 8.7 × 1013vg / kg, or 8.8 × 1013vg / kg, or 8.9 × 1013vg / kg, or 9.0 × 1013vg / kg, or 9.1 × 1013vg / kg, or 9.2 × 1013vg / kg, or 9.3 × 1013vg / kg, or 9.4 × 1013vg / kg, or 9.5 × 1013vg / kg, or 9.6 × 1013vg / kg, or 9.7 × 1013vg / kg, or 9.8 × 1013vg / kg, or 9.9 × 1013vg / kg, or 1.0 × 1014vg / kg. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, one or more buffers, one or more amino acids, one or more inorganic salts, one or more surfactants, and one or more solvents. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine, arginine, sodium chloride, magnesium chloride, a surfactant, and water. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248-0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15-0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX in an amount of 1.5 x 1012– 2.5 x 1013vg, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248- 0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15-0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; arginine – 0.348 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; L- arginine – 0.348 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX in an amount of 5 x 1012vg; L- arginine – 0.35 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.348 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; L-arginine – 0.348 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.1 mg, magnesium chloride hexahydrate – 0.203 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition: recombinant viral vector AAV5-FIX – 5 x 1012vg; L-arginine – 0.35 mg, L-histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml, pH 8.0-8.2. In some embodiments, the pharmaceutical composition is present in vials. In some embodiments, the pharmaceutical composition is present in vials with a filling volume of 1-25 ml, or 1-20 ml, or 1-12, or 1-10 ml, or 1-8 ml, or 1-6 ml, or 1-5 ml. In some embodiments, the pharmaceutical composition is present in vials with a filling volume of 1,2,3,4,5,6,7,8.9,10,11,12,13,14,15,16,17,18.19, or 20 ml. In some embodiments, hemophilia B is mild hemophilia B, or moderate hemophilia B, or severe hemophilia B. In some embodiments, hemophilia B is: (i) severe hemophilia B with FIX activity < 1 %; (ii) severe hemophilia B with FIX activity <1 IU / dl; (iii) moderate hemophilia B with FIX activity of 1-5 %; (iv) moderate hemophilia B with FIX activity of 1-5 IU / dl; (v) mild hemophilia B with FIX activity > 5%; (vi) mild hemophilia B with FIX activity of 5-40 IU / dl; (vii) hemophilia B without FIX inhibitor (inhibitor titer <0.6 BU); (viii) hemophilia B with FIX inhibitor (inhibitor titer ≥0.6 BU); (ix) hemophilia B with antibodies to AAV5; (x) hemophilia B with antibodies to AAV5 (antibody to AAV5 titer > 1:5); (xi) hemophilia B without antibodies to AAV5; or (xii) hemophilia B without antibodies to AAV5 (antibody to AAV5 titer < 1:5); In some embodiments, the recombinant virus of the vector AAV5-FIX comprises: 1) a nucleic acid that includes a nucleic acid with the nucleotide sequence of SEQ ID NO: 1 encoding the FIX (blood coagulation factor IX) protein; and^ 2) a capsid of the recombinant adeno-associated virus serotype 5.^ In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 having the amino acid sequence of SEQ ID NO: 3. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises AAV5 proteins VP1, VP2, and VP3. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO: 5. In some embodiments, the capsid of the recombinant adeno-associated virus serotype 5 comprises proteins VP1 with the amino acid sequence of SEQ ID NO: 3 with one or more point mutations, VP2 with the amino acid sequence of SEQ ID NO: 4 with one or more point mutations, and VP3 with the amino acid sequence of SEQ ID NO: 5 with one or more point mutations. In some embodiments, the nucleic acid includes the following elements in the 5'-end to 3'-end direction: a left-hand (first) ITR (inverted terminal repeats);^^ TTR promoter (transthyretin promoter);^^ an intron of the hBG1 gene (an intron-bearing fragment of the human β-globin gene);^^ a nucleic acid encoding the FIX (blood coagulation factor IX) protein with the nucleotide sequence of SEQ ID NO: 1;^^ an hGH1 polyadenylation signal (human growth hormone gene polyadenylation signal);^^ a right-hand (second) ITR.^ In some embodiments, the nucleic acid is represented by the nucleotide sequence of SEQ ID NO: 2.^ In some embodiments, the recombinant viral vector AAV5-FIX comprises: 1) a nucleic acid represented by the nucleotide sequence of SEQ ID NO: 2;^ 2) the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO: 5.^ In some embodiments, the administration of the recombinant viral vector AAV5-FIX is carried out by way of a single administration. In some embodiments, the administration of the recombinant viral vector AAV5-FIX is carried out by way of a single intravenous administration. In some embodiments, further comprises premedication, postmedication, and / or concomitant therapy. In some embodiments, further comprises premedication, postmedication, and / or concomitant therapy in a subject. In some embodiments, further comprises premedication, postmedication and / or concomitant therapy using glucocorticoid products. In some embodiments, further comprises premedication, postmedication and / or concomitant therapy using an immunosuppressive agent and / or a human coagulation factor IX product.https: / / www.vidal.ru / drugs / molecule / 2117 In some embodiments, the immunosuppressive agent is selected from a glucocorticoid, an antimetabolite, an alkylating agent, a cytostatic, a calcineurin inhibitor, an mTOR inhibitor, a monoclonal antibody, or one other immunosuppressant. In some embodiments, further comprises concomitant therapy using human coagulation factor IX products.https: / / www.vidal.ru / drugs / molecule / 2117 In some embodiments, further comprises the administration of glucocorticoids. In some embodiments, premedication, postmedication, and / or concomitant therapy are administered: (i) daily prior to administration of the recombinant viral vector AAV5-FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy are administered: (i) daily 1,2,3,4,5,6,7,8.9 or 10 days prior to administration of the recombinant viral vector AAV5- FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered one day prior to the administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered 24 hours (+ / - 60 minutes) prior to the administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered on the day of administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered daily post administration of the recombinant viral vector AAV5-FIX. In some embodiments, premedication, postmedication, and / or concomitant therapy is administered daily post administration of the recombinant viral vector AAV5-FIX in targeted, reduced, or pulse therapy. In some embodiments, premedication, postmedication and / or concomitant therapy is administered one day prior to administration of the recombinant viral vector AAV5-FIX, and daily post administration of the recombinant viral vector AAV5-FIX, including the day of administration. In some embodiments, premedication, postmedication and / or concomitant therapy is administered one day prior to administration of the recombinant viral vector AAV5-FIX, and daily post administration of the recombinant viral vector AAV5-FIX for 60 days, including the day of administration. In some embodiments, the glucocorticoid is selected from prednisolone, prednisone, hydrocortisone, cortisone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, fludrocortisone, fluticasone, mazipredone, or an available equivalent. In some embodiments, prednisolone is selected at a dose of 0.10-30 mg / kg / day; or 0.10-25 mg / kg / day; or 0.10-20 mg / kg / day; or 0.10-19 mg / kg / day; or 0.10-18 mg / kg / day; or 0.10-17 mg / kg / day; or 0.10-16 mg / kg / day; or 0.10-15 mg / kg / day; or 0.10-14 mg / kg / day; or 0.10-13 mg / kg / day; or 0.10-12 mg / kg / day; or 0.10-11 mg / kg / day; or 0.10-10 mg / kg / day; or 0.10-9 mg / kg / day; or 0.10-8 mg / kg / day; or 0.10-7 mg / kg / day; or 0.10-6 mg / kg / day; or 0.10-5 mg / kg / day; or 0.10-4 mg / kg / day; or 0.10-3 mg / kg / day; or 0.10-2 mg / kg / day; or 0.20-1.25 mg / kg / day; or 0.20-1.25 mg / kg / day; or 0.20-1.1 mg / kg / day; or 0.20-1.05 mg / kg / day; or 0.25-1.00 mg / kg / day. In some embodiments, prednisolone is administered at a dose of 0.10 mg / kg / day; or 0.15 mg / kg / day; or 0.20 mg / kg / day; or 0.25 mg / kg / day; or 0.30 mg / kg / day; or 0.35 mg / kg / day; or 0.40 mg / kg / day; or 0.45 mg / kg / day; or 0.50 mg / kg / day; or 0.55 mg / kg / day; or 0.60 mg / kg / day; or 0.65 mg / kg / day; or 0.70 mg / kg / day; or 0.75 mg / kg / day; or 0.80 mg / kg / day; or 0.85 mg / kg / day; or 0.90 mg / kg / day; or 0.95 mg / kg / day; or 1 mg / kg / day; or 1.05 mg / kg / day; or 1.10 mg / kg / day; or 1.15 mg / kg / day; or 1.20 mg / kg / day; or 1.25 mg / kg / day; or 1.30 mg / kg / day; or 1.35 mg / kg / day; or 1.40 mg / kg / day; or 1.45 mg / kg / day; or 1.50 mg / kg / day; or 2.0 mg / kg / day; or 3.0 mg / kg / day; or 4.0 mg / kg / day; or 5.0 mg / kg / day; or 6.0 mg / kg / day; or 7.0 mg / kg / day; or 8.0 mg / kg / day; or 9.0 mg / kg / day; or 10.0 mg / kg / day; or 11.0 mg / kg / day; or 12.0 mg / kg / day; or 13.0 mg / kg / day; or 14.0 mg / kg / day; or 15.0 mg / kg / day; or 16.0 mg / kg / day; or 17.0 mg / kg / day; or 18.0 mg / kg / day; or 19.0 mg / kg / day; or 20.0 mg / kg / day; or 25.0 mg / kg / day; or 30.0 mg / kg / day. Other glucocorticoids may be used at doses equivalent to the above doses of prednisolone. Examples. Example 1. Study of specific activity of ANB-002 product in hemophilia B model following single intravenous administration to blood coagulation factor IX gene knockout C57BL / 6-F9em1Smocmice The study was conducted on male С57BL / 6-F9em1Smocmice with knockout of the coagulation factor IX gene (hemophilia B model). The ANB-002 product was administered once into the tail vein at doses of 2.5×1012 vg / kg, 5×1012vg / kg, 2×1013vg / kg. The ANB-002 product is an infusion solution comprising a recombinant viral vector based on AAV5-FIX at 6.7×1011vg / ml and excipients: sodium chloride – 11.7 mg, L-histidine – 2.79 mg, L-arginine – 0.348 mg, magnesium chloride hexahydrate – 0.203 mg, Poloxamer 188 – 0.05 mg, water for injections ad 1 ml. Animals in the control group received a placebo (0.9% sodium chloride solution). Animals were divided into groups according to product doses and measurement time points (Table 1). Table1. Groups of animals Note: ♂ – males Blood samples were collected for analysis and tests were performed to measure the product's efficacy on day 3, weeks 3, 10, and 18 post single administration of ANB-002. Specific activity of ANB-002 was assessed according to the parameters "aPTT" (activated partial thromboplastin time), "blood loss mass" and "tail bleeding time"; also, determined was plasma factor IX (FIX) concentration in experimental animals. Following a single intravenous administration of the ANB-002 product at doses of 2.5×1012vg / kg and 5×1012vg / kg, the presence of FIX in mice plasma was observed from week 3 to 18 of the experiment. The groups of animals receiving the ANB-002 product at a dose of 2×1013vg / kg showed the presence of plasma FIX throughout the follow-up period. Tail bleeding time in animals in the groups that received the ANB-002 product at doses of 5×1012vg / kg and 2.5×1012vg / kg was significantly lower than that in the control group of animals at weeks 3 and 18, respectively. In the maximum dose group (2×1013vg / kg), the levels of the parameter were significantly lower compared to those of the control, starting from week 3 of the experiment until the end of the follow-up period (week 18). No statistically significant differences were observed in the parameter levels in the groups of animals that received the product at doses of 2.5×1012vg / kg, 5×1012vg / kg and 2×1013vg / kg. The blood loss mass in the groups of animals that received the ANB-002 product at a dose of 2.5×1012vg / kg was significantly lower than that in the control group of animals at week 3 of the experiment. Following administration of the ANB-002 product at a dose of 5×1012vg / kg, the parameter level was statistically significantly lower compared to that of the control from week 3 to 18 of the experiment. In the maximum dose group (2×1013vg / kg), the blood loss mass was significantly lower than that in the control group throughout the entire follow-up period (day 3 – week 18). No statistically significant differences in the "blood loss mass" parameter were observed between the levels in the groups of animals that received the ANB-002 product at doses of 5×1012vg / kg and 2×1013vg / kg. Following administration of the ANB-002 product at doses of 5×1012vg / kg and 2×1013vg / kg, aPTT was statistically significantly lower than that in the groups of animals that received placebo from week 3 to 18 of the experiment. At weeks 10 and 18 post administration of the product, the parameter in question in all groups of animals that received the ANB-002 product was significantly lower than that in the control group. No statistically significant differences in the "aPTT" parameter were observed between the values in the groups of animals that received the product at doses of 5×1012vg / kg and 2×1013vg / kg throughout the entire follow-up period. The data show that the ANB-002 product has specific activity following a single intravenous administration to C57BL / 6-F9em1Smocmice in the dose range of 2.5×1012– 2×1013vg / kg. Example 2. Study of toxicity and local irritant effect of ANB-002 product following a single intravenous administration into rabbits. The study was performed using male and female rabbits. The ANB-002 product was administered intravenously once at doses of 5×1012vg / kg and 5×1013vg / kg. The ANB-002 product is an infusion solution comprising a recombinant viral vector based on AAV5-FIX at 5.0×1012vg / ml and the following excipients: sodium chloride – 11.7 mg, L-histidine – 2.79 mg, L-arginine – 0.348 mg, magnesium chloride hexahydrate – 0.203 mg, Poloxamer 188 – 0.05 mg, water for injections ad 1 ml. Animals in control groups received a placebo whose composition corresponded to that of the excipients in the product. The animals were euthanized at weeks 3 and 21 of the experiment. Table 2 shows the groups of animals. Table 2. Groups of animals. Note: ♂ – males, ♀- females No animal deaths were observed during the study. The results of the experiment showed that following administration of the ANB-002 product at doses of 5×1012vg / kg and 5×1013vg / kg, the overall condition of the animals, body weight dynamics, feed and water consumption were comparable to those of the control. The ANB-002 product did not affect the hemostasis system, the functional state of the cardiovascular, respiratory, central nervous, urinary systems, hematological and biochemical parameters. No signs of ophthalmotoxicity were observed. Pathomorphological studies did not reveal any changes in organ mass coefficients, or any disorders in the structure of organs and tissues of experimental animals. The ANB-002 product did not cause a local irritant effect following a single intravenous administration into rabbits at doses of 5×1012vg / kg and 5×1013vg / kg. Example 3. Study of biodistribution of ANB-002 product following single intravenous administration to blood coagulation factor IX gene knockout C57BL / 6-F9em1Smocmice. Biodistribution of the ANB-002 product was studied using blood coagulation factor IX gene knockout С57BL / 6-F9em1Smocmice. The ANB-002 product was administered intravenously once at doses of 5×1012vg / kg, 2×1013vg / kg. The ANB-002 product is an infusion solution comprising a recombinant viral vector based on AAV5-FIX at 5.0×1011vg / ml and excipients: sodium chloride – 11.7 mg, L-histidine – 2.79 mg, L-arginine – 0.348 mg, magnesium chloride hexahydrate – 0.203 mg, Poloxamer 188 – 0.05 mg, water for injections ad 1 ml. Animals in the control groups received a placebo (0.9% sodium chloride solution). Biological material (brain, heart, kidney, adrenal glands, liver, lung, testicle, spinal cord, spleen, vein at the administration site, blood) was collected for analysis on day 3, week 3, 10 and 18 of the experiment. To assess biodistribution, the count of viral genome copies with the incorporated hFIX_R338L_GB2.0 gene and the level of transgene expression were determined. Table 3 shows the groups of animals. Table3. Groups of animals Note: ♂ – males The study revealed viral genomes in the tissues of all test organs, including liver, the target organ. The maximum level of viral genomes was detected on day 3 post administration of the product, thereafter at weeks 3, 10, and 18 of the experiment observed was a gradual decrease in the level of viral genomes in the tissues of animals’ organs. Post administration of the ANB-002 product, the highest level of viral genomes was detected in liver tissue throughout the experiment. In the blood of animals, the maximum level of viral genomes was observed on day 3 post administration of the product at all test doses, however, no viral genomes were detected from week 3 to 18 of the experiment. The highest expression level of the hFIX_R338L_GB2.0 gene was observed in the liver, the target organ. Post administration of the ANB-002 product, a dose-dependent increase in transgene expression was observed in liver tissues from week 3 to 10 of the experiment. At week 10 of follow- up, the expression level of the hFIX_R338L_GB2.0 gene in the liver reached plateau levels. During the follow-up period, an increase and reaching plateau levels in transgene expression were also observed In lung tissues but the expression level was significantly lower than that in liver tissues. Transgene expression in the brain, spinal cord, adrenal gland, heart, kidney, testis, spleen, and vein at the administration site was detected at various time points in individual animals in the groups receiving the ANB-002 product. Transgene expression in mice blood was detected in none of the animals throughout the entire follow-up period. Example 4. Biodistribution and environmental risk study of ANB-002 product following single intravenous administration to rabbits (Oryctolagus cuniculus). The biodistribution of the ANB-002 product was assessed as part of a toxicity and local irritancy study. The study was conducted using male and female rabbits. The ANB-002 product was administered intravenously once at doses of 5×1012vg / kg and 5×1013vg / kg. The ANB-002 product is an infusion solution comprising a recombinant viral vector based on AAV5- FIX at 5.0×1012vg / ml and the following excipients: sodium chloride – 11.7 mg, L-histidine – 2.79 mg, L-arginine – 0.348 mg, magnesium chloride hexahydrate – 0.203 mg, Poloxamer 188 – 0.05 mg, water for injections ad 1 ml. Samples of biological material (brain, heart, kidney, adrenal gland, liver, lung, testicle, ovary, cervical spinal cord, thoracic spinal cord, lumbar spinal cord, spleen, vein at the administration site, blood) were collected for analysis at weeks 3 and 21 of the experiment. To assess biodistribution, the count of viral genome copies with the incorporated hFIX_R338L_GB2.0 gene and the level of transgene expression were determined. Table 4 shows the groups of animals. Table4. Groups of animals The study results showed that at week 3 post administration of the ANB-002 product at a dose of 5×1012vg / kg, viral genomes were detected in the tissues of all analysed organs of the animals, except for the brain and thoracic spinal cord. In animals in groups receiving the ANB-002 product at a dose of 5×1013vg / kg, viral genomes were detected in the tissues of all organs analysed. The highest level of viral genomes in organ tissues was observed at week 3 post administration of the product. At week 21 of the experiment, the level of viral genomes in the tissues of the animals' organs decreased or reached plateau levels. Transgene expression in the brain, spinal cord, heart, kidney, lung, and vein at the administration site was detected at various time points in individual animals in the groups receiving the ANB-002 product. High-level expression of the hFIX_R338L_GB2.0 gene was observed in the target organ, the liver, at week 3 post administration of the ANB-002 product at doses of 5×1012vg / kg or 5×1013vg / kg; at week 21 of the experiment, the level of transgene expression in the liver reached plateau levels. Data showed that in the groups of animals receiving the ANB-002 product at doses of 5×1012vg / kg or 5×1013vg / kg, viral genomes in feces, saliva and urine samples were not detected at weeks 3 and 21 post administration of the product. The maximum level of viral genomes in the blood of animals was observed at week 3 post administration of the product, however, no viral genomes in the blood were observed at weeks 12 and 21 of the experiment in the group of animals receiving the dose of 5×1012vg / kg, as well as at week 21 post administration of the product at a dose of 5×1013vg / kg. Example 5. Open-label, non-comparative study of safety, pharmacodynamics and efficacy of ANB-002 product following a single administration in rising doses to patients with hemophilia B Study design: Clinical study No. ANB-002-1 / SAFRAN is an open-label, non-comparative study of safety, pharmacodynamics and efficacy of the ANB-002 product following a single administration in rising doses to patients with hemophilia B. The study is carried out in 2 stages: • Stage 1: Study of pilot efficacy and safety of the product at different doses to select a potentially therapeutic dose for further study. • Stage 2: Study of efficacy and safety of the ANB-002 product at a selected potentially therapeutic dose. Test product: ANB-002 is an adeno-associated vector (AAV5) gene therapy product designed to deliver a copy of the gene encoding coagulation factor 9 (FIX). The ANB-002 product is: Dosage form solution for infusions Composition 1 ml of the product contains: Active ingredient: recombinant viral vector AAV5-FIX – 5.0 × 1012vg; Excipients: sodium chloride – 11.7 mg, histidine – 2.79 mg, arginine – 0.35 mg, magnesium chloride hexahydrate – 0.20 mg, Poloxamer 188 – 0.05 mg, water for injection – ad 1 ml. Route and method of administration Intravenous infusion Dosage regimen Single administration Transportation and storage Product storage / transportation temperature – minus 80 °C to minus 60 °C Investigated doses: Mode of administration: The ANB-002 product is administered as a single intravenous infusion using an infusion pump set at a rate of 1 ml / min. If well tolerated, the rate may be increased by 1 ml / min every 30 min, but the total rate should not exceed 4 ml / min. Premedication regimen: This study does not require mandatory premedication; premedication may be conducted prior to ANB-002 administration if deemed necessary by the investigator. Concomitant therapy: Post administration of the ANB-002 product, the need for adjustment of the dose and frequency of administration of FIX concentrates for patients receiving them in prophylactic mode will be determined based on FIX activity results. Once FIX activity ≥ 5% is achieved, the subject will be required to switch to an on-demand concentrate administration regimen. Subjects achieving FIX activity in the range of 2–5% may be switched to on-demand administration or reduced dose / frequency of FIX concentrate administrations based on clinical performance and Investigator assessment. Resumption of prophylactic administration of concentrates should be considered if FIX activity is 2–5% in at least 2 consecutive measurements. In case of bleeding post administration of the test ANB-002 product, treatment should be conducted according to recommendations taking into account the actual FIX activity levels. Prophylactic administration of FIX concentrates is possible prior to intended medical interventions and in other situations where there is a risk of bleeding. Subjects included in subgroup B of cohort #3 will additionally receive glucocorticoids as concomitant therapy for three days prior to ANB-002 administration and for 15 weeks post administration. Use of glucocorticoids as concomitant therapy (subgroup B) Subjects included in subgroup B of cohort #3 will receive glucocorticoids according to the following regimen (expressed as prednisolone): • For 3 days prior to ANB-002 administration: 40 mg / day • Day 1 – Week 4: 40 mg / day • Weeks 5–6: 35 mg / day • Weeks 7-8: 30 mg / day • Weeks 9-10: 25 mg / day • Weeks 11-12: 20 mg / day • Week 13: 15 mg / day • Week 14: 10 mg / day • Week 15: 5 mg / day It is allowed to administer an equivalent dose of another glucocorticoid at a prednisolone- equivalent dose. Administration of glucocorticoids following "transaminitis" or decreased FIX activity If FIX activity decreases by >10% compared to the previous measurement, it is recommended to re-assess the factor activity. Such assessment should be carried out as soon as possible, but no later than 7 days from the date of results of the previous analysis. If decreased activity is detected again, glucocorticoid therapy should be prescribed according to the scheme presented below. Below is the recommended dosage regimen of oral glucocorticoids following transaminitis and decreased FIX activity. • Week 1: 60-100 mg / day (≈1 mg / kg, the initial dose is selected based on the clinical performance and medical history) • Week 2: 40–60 mg / day • Week 3: 40 mg / day • Week 4: 30 mg / day • Week 5: 25–30 mg / day • Week 6: 20* mg / day • Week 7: 15 mg / day • Week 8: 10-12.5 mg / day • Week 9: 10** mg / day * Starting at 20 mg / day, the following dose reduction schedule may be considered: continue at 20 mg / day until transaminase levels return to baseline, then reduce the dose by 5 mg / week until reaching 10 mg / day. **In case of prolonged administration of the product, the daily dose should be reduced gradually. The longer the glucocorticoid therapy has been, the slower the withdrawal of the maintenance dose. Upon achieving a therapeutic effect, the dose is gradually reduced by 5 mg, then by 2.5 mg at 3-5 day intervals, first canceling the later doses. In the absence of positive dynamics, provided that the product is well tolerated, it is possible to administer a dose of 60 mg / day for 2 weeks. It is not recommended to reduce the dose in the absence of decreased laboratory parameters. Depending on the individual clinical situation, tolerability and efficacy of therapy, the doses and duration of administration of glucocorticoids may differ from the scheme proposed above at the discretion of the physician-investigator. If necessary, glucocorticoids for intravenous administration can be used. The following transaminase elevations will be considered adverse events of special interest, regardless of severity, relatedness to the product, or presence / absence of severity criteria: • For subjects with screening levels >ULN: elevated transaminases ≥1.5 ULN; • For subjects with normal screening levels: >ULN AND twice the initial levels). Duration of therapy: Single administration. Study tasks: Tasks in the main period: • To study the profile of adverse reactions (AEs) following administration of the ANB-002 product • To determine the therapeutically effective and safe dose of ANB-002 product • To determine the immunogenicity of ANB-002 product • To determine the main pharmacodynamic parameters of ANB-002 product • To study the biodistribution of ANB-002 product Tasks in the follow-up period: • To study the profile of adverse reactions following administration of ANB-002 product • To determine the therapeutically effective and safe dose of ANB-002 product • To determine the immunogenicity of ANB-002 product • To determine the main pharmacodynamic parameters of ANB-002 product • To study the biodistribution of ANB-002 product The first stage of the study involves dose escalation in at least three cohorts and allows for inclusion of an intermediate dose cohort. Each cohort includes 1 to 9 subjects. In cohort #1, an ID will be assigned to a subject who will receive a single administration of the ANB-002 product at a dose of 2.5 x 1012vg / kg in the form of an intravenous infusion. Follow-up to assess dose-limiting toxicities (DLTs) will be carried out for 28 days. If there are no DLTs in the first subject in cohort #1, an ID will be assigned, and the second and third subjects in cohort #1 will be infused. Data obtained during the first 28 days post administration of the ANB-002 product will be used to decide on dose escalation; follow-up for events suspicious for DLTs will continue for 10 weeks. Once safety and FIX activity data for 28 days post administration of the test product are available for all 3 participants in cohort #1 of the study, the data are submitted to the Independent Data Monitoring Committee (IDMC). The IDMC meeting will review all available data on the safety and FIX activity in subjects included in cohort #1. Based on the assessment by the IDMC with the participation of the Sponsor, a decision will be made on whether enrollment to cohort #1 can be continued or whether enrollment to cohort #2 should be started. Also, the IDMC meeting should result in a decision on the dose of the ANB-002 product to be used in subjects in cohort #2. The dose to be administered in cohort #2 will be in the range of 2.5×1012vg / kg to 5×1012vg / kg. If there are no DLTs in cohorts #1 and #2, and after three subjects included in cohort #2 have completed at least 10 weeks of follow-up, the study will include cohort #3 whose subjects will receive the ANB-002 product at a dose of 2×1013vg / kg. Subjects in cohort 3 will be divided into two subgroups (subgroup A without concomitant receipt of glucocorticoids; subgroup B with concomitant receipt of glucocorticoids) of at least three subjects each. Subjects will be included in the subgroups in alternate manner. At least 10 weeks post infusion, subjects included in cohort #3 will be subjected to a pilot evaluation of the efficacy and safety of test product, and the IDMC meeting will be held. Based on the results of the analysis of data, the IDMC with the participation of the Sponsor will make a decision on which dose of the ANB-002 product can be considered potentially therapeutic and most acceptable for further study; 6 more subjects will be enrolled into the cohort with a potentially effective dose. If the dose of cohort #3 is selected as a therapeutic one, the most appropriate therapeutic regimen for further study should also be determined – with or without mandatory concomitant administration of glucocorticoids. This study attributes to DLTs any adverse event (AE) of grade 3 or higher according to CTCAE 5.0 that has a possible, probable, or definite relatedness to test product administration, with the exception of increased body temperature and / or transaminases. Increased body temperature can be considered a DLT, starting from grade 4 severity according to CTCAE 5.0, in the case of a possible, probable or definite relatedness with the test product administration (in this case, the duration of the AE, the need for medical therapy, the presence of concomitant diseases should be taken into account). DLTs will include the following transaminase elevations if they are incurable, regardless of severity, provided there is a possible, probable, or definite relatedness to ANB-002: for subjects with screening levels >ULN – transaminase elevation ≥1.5 ULN; for subjects with normal screening levels – >ULN AND twice the initial levels). For 10 weeks post administration of ANB-002, events suspicious for DLTs (AEs that meet the criteria for DLTs but occur after day 28 and before the end of 10-week period post administration) will be assessed. The second stage investigates the efficacy and safety of the ANB-002 product in a selected therapeutic dose; 6 more subjects will be included in the cohort. Inclusion criteria To participate in this study, subjects must meet all the inclusion criteria: 1. Provision of written informed consent to participate in the study. 2. Males with a confirmed diagnosis of hemophilia B aged 18 years or older at the time of signing the informed consent form. 3. Diagnosis of hemophilia B: • FIX activity ≤1% at screening; • FIX activity >1% to ≤2% (1–2%) at screening, provided there were at least 3 episodes of spontaneous bleeding during 52 weeks prior to signing the informed consent form (for subjects receiving on-demand FIX concentrate therapy) or presence of hemophilic arthropathy. Absence of a FIX inhibitor at screening (the presence of an inhibitor is considered confirmed with an inhibitor titer ≥ 0.6 BE) and in the medical history. 4. Administration of FIX concentrates for at least 150 exposure days. 5. Patients receiving FIX concentrates in prophylactic mode who have not required an increased dose or frequency of FIX concentrate administrations within 6 months prior to signing the informed consent, except for occasional dose increases prior to elective medical interventions and other events posing a risk for bleeding. 6. Willingness of subjects and their reproductively viable sexual partners to use reliable contraceptive methods until 3 consecutive sperm samples free of vector DNA have been obtained. This requirement does not apply to subjects who have undergone surgical sterilization. 7. Refusal of subjects from sperm donation provided that their reproductive function is preserved until 3 consecutive sperm samples free of vector DNA have been obtained. 8. Ability of the subject, in the opinion of the investigator, to comply with protocol procedures. Non-inclusion criteria Subjects are not eligible to participate in the study if they meet any of the following criteria: 1. History of use of any gene therapy product. 2. Presence of other blood / hematopoietic organ diseases besides hemophilia B. 3. Antibodies to AAV5 as determined by ELISA. If a subject is found to have an AAV5 antibody titer >1:5 at screening, the AAV5 antibody titer test may be repeated. Subjects with AAV5 antibody titers ≤1:5 on repeat testing may be included in the study. 4. Known allergy or intolerance to FIX concentrates or any component of ANB-002. 5. Known allergy or intolerance to glucocorticoids. 6. BMI <16 kg / m² or ≥35 kg / m². 7. Previous arterial or venous thrombosis (any venous thrombosis, pulmonary embolism, acute myocardial infarction, etc.). 8. Diagnosed HIV infection. A patient with HIV-1, HIV-2 antibodies receiving antiretroviral therapy may be included in the study if the following conditions are met: • CD4+ cell count >200 cells×mm3, • undetectable viral load (<50 copies / ml). 9. Hepatitis B, including in the medical history. 10. Acute or chronic hepatitis C: detectable HCV RNA at screening or use of hepatitis C antiviral therapy at screening. 11. Any active systemic infections or recurrent infections requiring systemic therapy present in the patient at the time of screening examination. 12. Presence of any other diseases accompanied by severe immunosuppression. 13. Laboratory parameters at screening: • Blood creatinine >1.5 ULN; • Platelet count <100 cells×109 / L; • Albumin <LLN; • AST, ALT, GGT, ALP >1.5 ULN; • Total bilirubin >1.5 ULN; • INR ^1.4. 14. Significant liver disease of any etiology, or conditions that may be a symptom of existing liver disease, including but not limited to: • Cirrhosis; • Presence of grade 3–4 fibrosis according to the METAVIR scale (or equivalent grade in case of using other assessment scales) based on the results of liver biopsy or non-invasive examination methods. 15. Lymphoproliferative diseases or malignant diseases with a remission duration of less than 5 years, with the exception of cured basal cell carcinoma. 16. History of malignant liver diseases. 17. Diseases requiring regular intake of systemic glucocorticoids. 18. Use of immunosuppressive agents (except glucocorticoids) 30 days prior to the administration of ANB-002. 19. Major surgery planned within 52 weeks post administration of ANB-002. 20. Known, including based on medical history, alcohol or substance addiction, psychoactive substance abuse or medication abuse, current evidence of alcohol / drug addiction or abuse that, in the opinion of the investigator, is a contraindication to hemophilia B therapy or limits compliance. 21. Simultaneous participation in other clinical studies, as well as previous participation in other clinical studies less than 3 months prior to signing the IC, previous participation in this study. Exception: subjects who withdrew from this study at screening. 22. Last administration of any experimental / investigational product within 1 month or 5 half-lives (whichever is longer) before signing the IC form. Interim results of the ANB-002-1 clinical study (data snapshot date 05.06.2024): Subject 06-01-01, cohort #1 (2.5 х 1012vg / kg) • Date of ANB-002 administration: 25.05.2023, dose: 240 х 1012vg, 48 ml • Age 29 years (born in 1994), weight 95 kg • Hemophilic arthropathy: yes • No infusion reactions and AEs were reported. • Concomitant diseases: class 1 obesity, fatty liver disease (time of onset unknown, ongoing) • During the study, no DLTs were reported. All reported AEs were grade 1 AEs (except for grade 2 COVID-19 coronavirus infection) and, in the opinion of the investigator, were not related to therapy. • No inhibitor or antibodies to the FIX protein were detected. • Glucocorticoids were not prescribed. Table 5. Data on FIX activity, bleeding episodes, and replacement therapy, subject 06-01-01 Subject 08-01-02, cohort #1 (2.5 х 1012vg / kg) • Date of ANB-002 administration: 29.06.2023; dose: 130 х 1012vg, 26 ml • Age 26 years (1996 birth year), weight 52 kg • Hemophilic arthropathy: yes • Concomitant diseases: epilepsy (levetiracetam, lacosamide), allergy to cat hair. • During the study, no DLTs were reported. • All reported AEs were grade 1 AEs and, according to the investigator, were not related to therapy. Two grade 1 AEs of special interest (elevated ALT) were reported, which resolved spontaneously and, in the opinion of the investigator, were not related to therapy. No inhibitor or antibodies to the FIX protein were detected. • Receipt of prednisolone since 27.04.2024. Reasons for prescription: activity at week 38 – 18.6%, activity at weeks 42 and 44 – 14.7% and 16.3%, which corresponded to a relative drop by 21% and 12.4% compared to week 38. Also, along with the relative decrease in activity from week 42, the patient has an ALT level that is 1.5 times higher than the levels at screening, however ALT levels remain within the normal range (for this patient, ALT levels at 18 U / L and AST levels at 24 U / L were considered to be 1.5 times higher than the screening levels). According to the protocol, prednisolone was prescribed (more detailed indications for prescribing GCs are shown in Appendix 1). Prednisolone intake schedule: From 27.04.2024 (week 43) – 50 mg / day From 04.05.2024 (week 44) – 40 mg / day From 18.05.2024 (week 46) – 30 mg / day From 25.05.2024 (week 47) – 25 mg / day From 01.06.2024 (week 48) – 20 mg / day (continuation) Table 6 Data on FIX activity, bleeding episodes, and replacement therapy, subject 08-01-02 Subject 12-01-03, cohort #1 (2.5 х 1012vg / kg) • Date of ANB-002 administration: 05.07.2023; dose: 220 х 1012vg, 44 ml • Age 38 years (1985 birth year), weight 88 kg • Hemophilic arthropathy: yes • Concomitant diseases: fatty liver, history of hepatitis C • During the study, no DLTs were reported. • All reported AEs were grade 1-2 AEs and, according to the investigator, in most cases were not related to therapy. Three cases of AE "headache" were considered to be treatment-related. During the study, this patient experienced multiple episodes of headaches that resolved spontaneously or were relieved by taking NSAIDs. The investigational site's physicians and the patient were advised by the NCMD about the need for further examination to rule out possible thrombotic complications, but the patient refused additional examination, including after being informed again. • Glucocorticoids were not prescribed. • No inhibitor or antibodies to the FIX protein were detected. Table 7 Data on FIX activity, bleeding episodes, and replacement therapy, subject 12-01-03 Subject 12-03-04, cohort #1 (2.5 х 1012vg / kg) • Date of ANB-002 administration: 09.08.2023, dose: 260 х 1012vg, 53 ml • Age 34 years (born in 1988), weight 104 kg • Hemophilic arthropathy: yes • Concomitant diseases: superficial gastritis, gastroesophageal reflux disease, arterial hypertension. • During the study, no DLTs were reported. No bleeding was observed. All reported AEs were grade 1-2 AEs and in most cases, according to the investigator, were not related to therapy. The following events were considered treatment-related: a grade 1 event of blood pressure elevation (regarded as an infusion reaction symptom) on the day of ANB-002 administration and a grade 1 event of elevated AST levels. • Glucocorticoids were not prescribed. • The patient was reported to have a single relative decrease in activity exceeding 10% (activity at week 28 – 56.3%, activity at week 32 – 48.5%, relative drop – 13.9%), which was not confirmed after reassessment at an unscheduled visit. Transaminases not only did not exceed ULN (except for one episode of elevated AST levels mentioned above), but also did not exceed screening levels by 1.5 times. • No inhibitor or antibodies to the FIX protein were detected. Table 8 Data on FIX activity, bleeding episodes, and replacement therapy, subject 12-03-04 Subject 06-02-05, cohort #2 (5 х 1012vg / kg) • Date of ANB-002 administration: 16.10.2023, dose: 370 х 1012vg, 53 ml • Age 28 years (1995 birth year), weight 75 kg • Hemophilic arthropathy: yes • No significant concomitant diseases • During the study, no DLTs were reported. No bleeding was observed. All reported AEs were grade 1-2 AEs and in most cases, according to the investigator, were not related to therapy. Two AEs were considered treatment-related: grade 1 AE "elevated ALT levels" and grade 1 AE "elevated AST levels". • No inhibitor or antibodies to the FIX protein were detected. • Receipt of prednisolone since 09.04.2024. Reasons for prescription: activity at week 22 – 50.6%, activity at weeks 24 and 25 – 45.0% and 41.1%, which corresponded to a relative drop by 11.1% and 18.8% compared to week 22. According to the protocol, prednisolone was prescribed. Prednisolone intake schedule: From 09.04.2024 (week 26) – 60 mg / day From 23.04.2024 (week 28) – 55 mg / day From 26.04.2024 (week 28) – 50 mg / day From 29.04.2024 (week 29) – 45 mg / day From 02.05.2024 (week 29) – 40 mg / day From 05.05.2024 (week 29) – 35 mg / day From 08.05.2024 (week 30) – 30 mg / day From 11.05.2024 (week 30) – 25 mg / day From 14.05.2024 (week 31) – 20 mg / day From 17.05.2024 (week 31) – 15 mg / day From 20.05.2024 (week 32) – 10 mg / day From 23.05.2024 (week 32) – 5 mg / day. Due to decreased factor activity by more than 10%, resumption of administration of GCs at a dose of 30 mg / kg from 04.06.2024 was discussed with investigators. Table 9 Data on FIX activity, bleeding episodes, and replacement therapy, subject 06-02-05 Patient 07-02-06, cohort #2 (5 х 1012vg / kg) • Date of ANB-002 administration: 27.11.2023, dose: 375 х 1012vg, 75 ml • Age 21 years (2002 birth year), weight 75 kg • Hemophilic arthropathy: yes • Concomitant diseases: myopia, irritable bowel syndrome, allergy. Urolithiasis in childhood, not examined at present time. • During the study, no DLTs were reported. The reported AEs were grade 1–2 AEs and, in the opinion of the investigator, were not related to therapy, except for the case of grade 1 infusion reaction (on the day of ANB-002 administration, weakness and an increase in body temperature to 37.5C were observed in the patient). • No inhibitor or antibodies to the FIX protein were detected. • Receipt of prednisolone since 10.04.2024. Reasons for prescription: activity at week 16 – 50.6%, activity at weeks 18 and 19 – 42.7% and 42.0%, which corresponded to a relative drop by 15.6% and 17% compared to week 16. According to the protocol, prednisolone was prescribed. Prednisolone intake schedule: From 10.04.2024 (week 20) – 75 mg / day From 17.04.2024 (week 21) – 60 mg / day From 20.04.2024 (week 21) – 50 mg / day From 24.04.2024 (week 22) – 40 mg / day From 01.05.2024 (week 23) – 30 mg / day From 16.05.2024 (week 25) – 20 mg / day From 22.05.2024 (week 26) – 15 mg / day From 29.05.2024 (week 27) – 10 mg / day (continuation) Table 10 Data on FIX activity, bleeding episodes, and replacement therapy, subject 07-02-06 Patient 07-03-07, cohort #2 (5 х 1012vg / kg) 1. Date of ANB-002 administration: 29.11.2023, dose: 310 х 1012vg, 62 ml 2. Age 37 years (1986 birth year), weight 62 kg 3. Hemophilic arthropathy: yes 4. Concomitant diseases: osteoarthritis of the left knee joint, allergy 5. During the study, no DLTs were reported. No bleeding was observed. All reported AEs were grade 1-2 AEs and, according to the investigator, were not related to therapy. No inhibitor was detected. Antibodies to the FIX protein were detected on day 1, week 1, week 2, week 3, week 4. 6. Receipt of prednisolone since 13.04.2024. Reasons for prescription: activity at week 16 – 18.4%, activity at weeks 18, 19 and 20 – 15.9%, 16.0% and 14.2%, which corresponded to a relative drop by 13.6%, 13.0% and 22.8% compared to week 16. According to the protocol, prednisolone was prescribed. Prednisolone intake schedule: From 13.04.2024 (week 20) – 65 mg / day From 20.04.2024 (week 21) – 50 mg / day From 27.04.2024 (week 22) – 40 mg / day From 04.05.2024 (week 23) – 30 mg / day From 11.05.2024 (week 24) – 25 mg / day From 18.05.2024 (week 25) – 20 mg / day From 25.05.2024 (week 26) – 15 mg / day From 01.06.2024 (week 27) – 10 mg / day (continuation) Table 11 Data on FIX activity, bleeding episodes, and replacement therapy, subject 07- 03-07 Patient 12-05-08, cohort #3 (subgroup А) 2 х 1013vg / kg • Date of ANB-002 administration: 29.03.2024, dose: 162 х 1013vg, 324 ml • Age 37 years (1986 birth year), weight 81 kg • Hemophilic arthropathy: yes • Associated diseases: history of hepatitis C, osteotomy of the right hip, arthroplasty of the left knee joint, cholelithiasis, • During the study, no DLTs were reported. No bleeding was observed. • At week 4 (20.04.2024), the following patient data were reported: CPK (creatine phosphokinase) – 14,284 U / L (grade 4), ALT – 59 U / L (grade 1), AST – 144 U / L (grade 2), LDH – 581 U / L (grade 2). There were no clinical manifestations. According to the investigator, feeling well, the patient had excessive physical activity. According to the investigator, of these events, increased ALT and AST levels were related to the product. Elevations in LDH and CPK were considered questionably related. In the blood test dated 26.04.2024 CPK was 377 U / L; AST, ALT, LDH were normal. • No inhibitor or antibodies to the FIX protein were detected. • Receipt of prednisolone since 23.04.2024. Reasons for prescription: glucocorticoids were prescribed due to reported therapy-related elevations in transaminase activity. According to the protocol, prednisolone was prescribed (more detailed indications for prescribing GCs are shown in Appendix 1). Prednisolone intake schedule: From 23.04.2024 (week 4) – 80 mg / day From 09.05.2024 (week 7) – 60 mg / day From 20.05.2024 (week 8) – 40 mg / day From 27.05.2024 (week 9) – 30 mg / day From 05.06.2024 (week 10) – 20 mg / day Table 12 Data on FIX activity, bleeding episodes, and replacement therapy, subject 12-05-08 Detailed information on the reported adverse reactions (AEs) related to the product, and the results of blood biochemistry tests (ALT, AST) for each subject are shown in Tables 13–14.tsrtosipni9 29yaPmno2 3i yayayaD Td ata D D D n ar6 16 0-11 3.faoe - -1.p1e-111t pa 3 -13- 5 32as22 2no Didec0 20202isec3319 refn1e - 1 -2- vo r 11 1eru -31-1A R 3 -tc2232D a Dco 020202deeMn g d eP telelelnisaTleobits biss bisssudRsso PoPoP edo de dcdedeendnd raEEn / E / C e / O mded do ctve eSl d ovlvuseoln so aese T O RR RP.sserelbele diblo usac abcacictraenektilptil til ocMato Npo paNpo paNpaocytiulr g e–veoo o sS N N N C e G,n dt 1oac 4irutd G 1a1 1ltosrp uap Ery o Aunats do detp si ( )44 2ye–tnedsP TfaetC,asS.leGsotoo oaltcRsN N Ncej fa naboiceere u Et ogrAps lnitsooosN N NhcL oo ometD TsaN N N yesr-re–ofnsonm iso,wo v,,iot,reul(erf )gn )C O eCizel S ntcpe gie 5. eff,oiuftcna Iem ryvsetFaFhtdaOr7g3e(nusnm srentaeor isoidteecrrsufn ase ooe efre InrN NYervsit pdnafeo / toaitci–T )atres daclpPtdsies s / da nesaparsnetixmo,tneeoiaesaefsnoitaloetrcnilv Lrctarda a / ar enigictnies r g n n,as ueseto / slitsoisoiteirdere. / E / C Tse3 TO L vT rnS cnie evufcauj dco svd1A P S AIAnImvaelnInIernInarpnoa–el56E btcre 0A aejb0- -:T bum)2 uD02-06 -et7 o S nI(00Ntsrtosipni 93 3 y n6 2 2aPmoityayayaD Td a a D D D n ar 03 5 5 -2 2.faoep0- -14 41.5 etp -30-40-42aasi202 2 no D dec20 2 0 2isec610 0refn2e -0 -24 -v4 or 1 0 0A er - 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it6 - 7 - 7 - 7 - 7 - 8- - - - - - - - - - - - - - - - -1-2- etce0 0 0 0 0 08 08 08 08 09 09 090001 1 2 2 1 3455 r- - - - - - - - - - - -0-1-1-1-1-1-1-1-0-0-0 0 0ll32 333333333333333333344 -4 -4 -4 a 0202020202020202020202 2 2 2 2 2 2 2 2 2 2 2 2 2 moc2 2 2 2 2 2 2 2 2 2 2 02 02 02 02 02 02 02 02 02 02 02 02 02 02 )t1)4isyayiavtDD ne )2)4) ) ) ) ) ) )11) ) ) ) ) ) ) )m1 ti16 1 8 1 0 2 2 2 4 2 6 2 8 3tititik e k eee2k3k4k5k6k7k8k9keru ksisseevk k k k k k k kisdeeeeeeeeeeeeeeeevisdvidvd4g W(We(eeeeeeeeeeeeeeea5eWelWWWWWWWelelelnin1 / 2W(WWWWWWWm(u d( ( ( ( ( ( (W(u d u d u dtie 1 / ( ( ( ( ( ( (1 2 3 4 5 6 7t1e2 3456789 heheheh si er tisitisitisitisitisitisitisiti8siti9sitiae1sipetisics1ti1ti1ti1ti1ti1ti1ti1ticnsisisisisisisisi scnscnsn VcS V V V V V V V V V V R V U V V V V V V V V U U Ufostinu(retemarap )tyrneotm)arerL / U ous(b T aaeL L m A sn2 ci8aie8.h3:) sla81ps ac8:):)ar ruaMg gae :moy(C: rek( (tdsh me e egcanesagieD A R G M Hreb muntc3ej0-b)1 uD0- SI(21 noitlalalalalalal l l l l l l l l l l l l l l l l l lai a a a a a a a a a a a a a a a a a a avemrm m m m m m m m m m m m mororororororororororororormormormormormormormormormormormoro D N N N N N N N N N N N N N N N N N N N N N N N N N f ola timmrilo n 73737373737373737373737373737373737373737373737373 f ola timmrilo n 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 tluseR 02 42 91 91 91 81 91 02 91 02 32 42 62 42 62 22 12 02 22 62 91 22 12 92 32 5 1 5 00 1 8 1 5 2 1 08 05 1 2 2 0 35 04 1 6 2 3 01 1 4 2 7 01 2 5 09 1 9 06 2 0 1 42 l n aio - it6 - 7 - 7 - 7 - 7 - 8- - - - - - - - - - - - - - - - -1-2- etce0 0 0 0 0 08 08 08 08 09 09 090001 1 2 2 1 3455 r- - - - - - - - - - - -0-1-1-1-1-1-1-1-0-0-0 0 0ll32 333333333333333333344 -4 -4 -4 a 0202020202020202020202 2 2 2 2 2 2 2 2 2 2 2 2 2 moc2 2 2 2 2 2 2 2 2 2 2 02 02 02 02 02 02 02 02 02 02 02 02 02 02 )t1)4isyayiavtDD ne )2)4) ) ) ) ) ) )11) ) ) ) ) ) ) )m1 ti16 1 8 1 0 2 2 2 4 2 6 2 8 3tititik e k eee2k3k4k5k6k7k8k9keru ksisseevk k k k k k k kisdeeeeeeeeeeeeeeeevisdvidvd5g W(We(eeeeeeeeeeeeeeea5eWelWWWWWWWelelelnin1 / 2W(WWWWWWWm(u d( ( ( ( ( ( (W(u d u d u dtie 1 / ( ( ( ( ( ( (1 2 3 4 5 6 7t1e2 3456789 heheheh si er tisitisitisitisitisitisitisiti8siti9sitiae1sipetisics1ti1ti1ti1ti1ti1ti1ti1ticnsisisisisisisisi scnscnsn VcS V V V V V V V V V V R V U V V V V V V V V U U Ufostinu(retemarap )tyrneom)tarerL / u U os(b T aaeS L m A sn2 ci8aie8.h3:) sla81ps ac8:):)ar ruaMg gae :moy(C: rek( (tdsh me e egcanesagieD A R G M Hreb muntc3ej0-b)1 uD0- SI(21 noitlalalalalalal l l l l l l l l l l l l l l l l lai a a a a a a a a a a a a a a a a a avemrm m m m m m m m m m m m mororororororororororororormormormormormormormormormormoro D N N N N N N N N N N N N N N N N N N N N N N N N f ola timmrilo n 151515151515151515151515151515151515151515151515 f ola timmrilo n 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 11 tluseR 32 32 82 42 32 32 72 92 82 52 72 0372 32 42 72 82 22 92 1382 2372 33 8 2 9 04 1 1 2 8 2 4 01 1 8 1 5 2 2 09 06 1 0 33 1 7 2 1 1 5 2 9 02 2 5 09 1 882 l n aio - it7 - 8 - 8 - 8- - - - - - - - - - - - - - - - -1-0-2- etce0 0 0 08 09 09 09 09 00 1 0001 1 2 2 1 1 2 2 344 r- - - - - - - - - -1-1-1-1-1-1-1-0-0-0 0 0 0 0l3333333333333333344 -4 -4 -4 -4 -4 al2020202020202020202 2 2 2 2 2 2 2 2 2 2 2 2 2 2 moc2 2 2 2 2 2 2 2 2 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 ) 1)4yayaDD)0)2)4)6)8)0) ) ) )1 k1) ) ) ) ) ) ) )1 1 1 1 1 22 2 4 2 6 2tisek eee2itisti8 s3k3ek4ek5ek6ek7ek8ek9k k e k k k k k k k k eeeeeeeeeeeeeeeeevidvidvk dee65g W(W(e e e e e eeeeeWWWWWWWWWelueluelu W ni1 / 2W(W(W(W(W(W(W(W( ( ( ( ( ( ( ( ( ( d d d (n tie 1 / 12 3 4 5 6 7 8 90 1 1 1 2 1 3 1 4 1 5 1 6 1 78e9 heheh si er ticsitisitisitisitisitisitisitisitisitisitisitisitisitisitisitisiti1siti1sitisicscnscns1tinsiV S V V V V V V V V V V V V V V V V V V V U U U Vfostinu(retemarap )tyrne )otmLa / rerousU(b T aaeL L m A s ci4n3a5 is e400.h:)a la1 2psr c:u :) )argae aMgmoy(C::r(e ek( tdsh me egcanesagieD A R G M Hreb muntc4ej0-b)3 uD0- SI(21lanmro o itlal l l l l l l l l lnl l l l l l l l l l l lai a a a a a a a a a a e a a a a a a a a a a a amm m m m m m mv ve rororororororormormormormo obrmormormormormormormorm m m mororororo D N N N N N N N N N N N A N N N N N N N N N N N N f ola timmrilo n 737373737373737373737373737373737373737373737373 f ola timmrilo n 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 51 tluseR 42 92 62 62 52 42 330372 82 82 830382 72 62 3352 62 1333031382 8 2 9 04 1 1 2 8 2 4 01 1 8 1 5 2 2 09 06 1 0 33 1 7 2 1 1 5 2 9 02 59882 l n aio - it7 - 8- - - - - - - - - - - - - - - -2-0-1-1-0-2- etce0308 308 308 309 309 309 30900001 1 2 2 1 1 2 2 344 r- - - - - - - -30-31-31-31-31-31-31-31-31-30-40-40-40-40-40-40-4 all202020202020202 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 moc2 2 2 2 2 2 2 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 ) 1)4yayaDD)0)2)4)6) ) ) ) ) )1 k1) ) ) ) ) ) ) )1 1 1 18 1 0 2 2 2 4 2 6 2tististi8 3ek eee2k3ek4k5k6k7k8 9k k k k k k k k kivisviv k eeeeeeeek k eeeeeeeeeeeeeeeeeeeeeeeeed d dee75g W(W(WWWWWWWWWelueluelW ni1 2W(W(W(W(W(W(W(W( ( ( ( ( ( ( ( ( ( d du d(n / tie 1 / 12 3 4 5 6 7 8 90 1 1 1 2 1 3 1 4 1 5 1 678e9 heheh si er ticsitisitisitisitisitisitisitisitisitisitisitisitisitisitisiti1siti1siti1sitisicscnscns1tinsiV S V V V V V V V V V V V V V V V V V V V U U U Vfostinu(retemarap )tyrneotm)La / rerousU(b T aaeS L m A s ci4n3a5 is e400.h:)a la1 2psr c:u :) )argae aMgmoy(C::r(e ek( tdsh me egcanesagieD A R G M Hreb muntc4ej0-b)3 uD0- SI(21lalalanmromrnmrot a a a a an o aa a a ao o il l l l l lnl l l l itlalalalalnl l l l l lai e e a e a a a a a amm m mv vaiv ve rororormoro ombro ombrmormormormove rmormormormoro ombrmormormormormoro D N N N N N A N A N N N N D N N N N N A N N N N N N f ola tirf la meoptimmrilo n 1515151 p 51515151515151515 Umrilo n 737373737373737373737373 f olarf leoa timmrwtimilo n 11 11 11 11 11 11 1 o 1 11 11 11 11 11 L mrilo n 51 51 51 51 51 51 51 51 51 51 51 51 tlutls u e R 52 3482 12 52 9534959392 938se3 R 52 1332 22 74 2 41 535302 02 1312 891 630574887 891 aio1 2 0 0 1 2 2 2 0 0 1630574887 l n - it3 - 3 - 4 - 4 -2n1 2 0 0 1 2 2 2 0 0 1 24 - 4 - 4 - 4 - 5 - 5 - 5 - 5lo - 3 - 3 - 4 - 4 - 4 - 4 - 4 - 4- - - -etce0ll40- 2 40- 2 40- 2 40- 2 40- 2 40f-aiit5555 r - 2 40- 2 40- 2 40- 2 40- 2 40- 2 4or 2etetce0-0-0-0-0-0-0-0-0-0-0-0- ll42 42 42 42 42 42 42 42 42 444 a 000000002 02 02 02 0 aa 2 D m 02 02 0 2 2 2 moc2 2 2 2 2 2 2oc2 02 02 02 02 02 02 02 02 02 ) 1)4)1)4yayayayaDD1 t D D tk1k)2)3) i4si )5)6)7)8)1 19k k)2)3) i4si ) ) ) ) )eeeek e k eekveeed k elek eek eek keeeek k kv 5 6 7 8 9eeeeeeeeeeed k k k k k8eleeeeeeeeee 5g W(W(u g W(W(ni1 2W(W(W( dW(W(W(W(W( ni1 2W(W(Wu (dW(W(W(WW n / / en / / e( (tie 1si er ti1csiti2siti3siti4sitih5sicsti6 7 8 9 e 1 1 2 3 4h5 6 7 8 9nsitisitisitisitisitisi er ticsitisitisitisitisicstinsitisitisitisitisiV S V V V V V U V V V V V V S V V V V V U V V V V Vfofsoti sntiu n(u(rerteetemamraap )rta)yrnept)y neo)tmLrarer / otmL / Ua erU ous(rous(baT b TaeL aaeS L m A L m A s ci7didh3 o6 l8s7io 6 8 p:)oe .gl11 ci3loe .l 11na8: :)hp:)gna8 :)arsrgaeoM)gm(arsroM:)gmoy(M:rek( tgaeM:rek( (tme e:edsh oygcanesag(ieme e:edshg gcanesaieD A R G M H D A R G M Hrerbeb mu muntc8nej0-tc8 0-)5ej5 buD0- b)D0- SI(21 u SI(21

Claims

1. Claims.

1. A method for treating hemophilia B, comprising administering the recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg.

2. The method for treating according to claim 1, wherein the dose is 1.0 × 1012vg / kg to 1.0 × 1014vg / kg, or 1.0 × 1012vg / kg to 9.9 × 1013vg / kg, 1.0 × 1012vg / kg to 9.8 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.7 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.6 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.5 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.4 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.3 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.2 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.1 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.0 × 1013vg / kg, or 1.1 × 1012vg / kg to 8.9 × 1013vg / kg, or 1.2 × 1012vg / kg to 8.8 × 1013vg / kg, or 1.3 × 1012vg / kg to 8.7 × 1013vg / kg, or 1.4 × 1012vg / kg to 8.6 × 1013vg / kg, or 1.5 × 1012vg / kg to 8.5 × 1013vg / kg.

3. The method for treating according to claim 2, wherein the dose is 1.0 × 1012vg / kg to 2.0 × 1012vg / kg, or 2.0 × 1012vg / kg to 3.0 × 1012vg / kg, or 2.3 × 1012vg / kg to 2.8 × 1012vg / kg, or 2.4 × 1012vg / kg to 2.6 × 1012vg / kg, or 3.0 × 1012vg / kg to 4.0 × 1012vg / kg, or 4.0 × 1012vg / kg to 5.0 × 1012vg / kg, or 4.5 × 1012vg / kg to 5.5 × 1012vg / kg, or 4.8 × 1012vg / kg to 5.3 × 1012vg / kg, or 4.9 × 1012vg / kg to 5.1 × 1012vg / kg, or 5.0 × 1012vg / kg to 6.0 × 1012vg / kg, or 6.0 × 1012vg / kg to 7.0 × 1012vg / kg, or 7.0 × 1012vg / kg to 8.0 × 1012vg / kg, or 8.0 × 1012vg / kg to 9.0 × 1012vg / kg, or 9.0 × 1012vg / kg to 1.0 × 1013vg / kg, or 1.0 × 1013vg / kg to 2.0 × 1013vg / kg, or 1.5 × 1013vg / kg to 2.5 × 1013vg / kg, or 1.8 × 1013vg / kg to 2.3 × 1013vg / kg, or 1.9 × 1013vg / kg to 2.1 × 1013vg / kg, or 2.0 × 1013vg / kg to 3.0 × 1013vg / kg, or 3.0 × 1013vg / kg to 4.0 × 1013vg / kg, or 4.0 × 1013vg / kg to 5.0 × 1013vg / kg, or 4.5 × 1013vg / kg to 5.5 × 1013vg / kg, or 4.8 × 1013vg / kg to 5.3 × 1013vg / kg, 1013vg / kg, or 4.9 × 1013vg / kg to 5.1 × 1013vg / kg, or 5.0 × 1013vg / kg to 6.0 × 1013vg / kg, or 6.0 × 1013vg / kg to 7.0 × 1013vg / kg, or 7.0 × 1013vg / kg to 8.0 × 1013vg / kg, or 8.0 × 1013vg / kg to 9.0 × 1013vg / kg, or 9.0 × 1013vg / kg to 1.0 × 1014vg / kg.

4. The method for treating according to claim 3, wherein the dose is 1.0 × 1012vg / kg, or 1.1 × 1012vg / kg, or 1.2 × 1012vg / kg, or 1.3 × 1012vg / kg, or 1.4 × 1012vg / kg, or 1.5 × 1012vg / kg, or 1.6 × 1012vg / kg, or 1.7 × 1012vg / kg, or 1.8 × 1012vg / kg, or 1.9 × 1012vg / kg, or 2.0 × 1012vg / kg, or 2.1 × 1012vg / kg, or 2.2 × 1012vg / kg, or 2.3 × 1012vg / kg, or 2.4 × 1012vg / kg, or 2.5 × 1012vg / kg, or 2.6 × 1012vg / kg, or 2.7 × 1012vg / kg, or 2.8 × 1012vg / kg, or 2.9 × 1012vg / kg, or 3.0 × 1012vg / kg, or 3.1 × 1012vg / kg, or 3.2 × 1012vg / kg, or 3.3 × 1012vg / kg, or 3.4 × 1012vg / kg, or 3.5 × 1012vg / kg, or 3.6 × 1012vg / kg, or 3.7 × 1012vg / kg, or 3.8 × 1012vg / kg, or 3.9 × 1012vg / kg, or 4.0 × 1012vg / kg, or 4.1 × 1012vg / kg, or 4.2 × 1012vg / kg, or 4.3 × 1012vg / kg, or 4.4 × 1012vg / kg, or 4.5 × 1012vg / kg, or 4.6 × 1012vg / kg, or 4.7 × 1012vg / kg, or 4.8 × 1012vg / kg, or 4.9 × 1012vg / kg, or 5.0 × 1012vg / kg, or 5.1 × 1012vg / kg, or 5.2 × 1012vg / kg, or 5.3 × 1012vg / kg, or 5.4 × 1012vg / kg, or 5.5 × 1012vg / kg, or 5.6 × 1012vg / kg, or 5.7 × 1012vg / kg, or 5.8 × 1012vg / kg, or 5.9 × 1012vg / kg, or 6.0 × 1012vg / kg, or 6.1 × 1012vg / kg, or 6.2 × 1012vg / kg, or 6.3 × 1012vg / kg, or 6.4 × 1012vg / kg, or 6.5 × 1012vg / kg, or 6.6 × 1012vg / kg, or 6.7 × 1012vg / kg, or 6.8 × 1012vg / kg, or 6.9 × 1012vg / kg, or 7.0 × 1012vg / kg, or 7.1 × 1012vg / kg, or 7.2 × 1012vg / kg, or 7.3 × 1012vg / kg, or 7.4 × 1012vg / kg, or 7.5 × 1012vg / kg, or 7.6 × 1012vg / kg, or 7.7 × 1012vg / kg, or 7.8 × 1012vg / kg, or 7.9 × 1012vg / kg, or 8.0 × 1012vg / kg, or 8.1 × 1012vg / kg, or 8.2 × 1012vg / kg, or 8.3 × 1012vg / kg, or 8.4 × 1012vg / kg, or 8.5 × 1012vg / kg, or 8.6 × 1012vg / kg, or 8.7 × 1012vg / kg, or 8.8 × 1012vg / kg, or 8.9 × 1012vg / kg, or 9.0 × 1012vg / kg, or 9.1 × 1012vg / kg, or 9.2 × 1012vg / kg, or 9.3 × 1012vg / kg, or 9.4 × 1012vg / kg, or 9.5 × 1012vg / kg, or 9.6 × 1012vg / kg, or 9.7 × 1012vg / kg, or 9.8 × 1012vg / kg, or 9.9 × 1012vg / kg, or 1.0 × 1013vg / kg, or 1.1 × 1013vg / kg, or 1.2 × 1013vg / kg, or 1.3 × 1013vg / kg, or 1.4 × 1013vg / kg, or 1.5 × 1013vg / kg, or 1.6 × 1013vg / kg, or 1.7 × 1013vg / kg, or 1.8 × 1013vg / kg, or 1.9 × 1013vg / kg, or 2.0 × 1013vg / kg, or 2.1 × 1013vg / kg, or 2.2 × 1013vg / kg, or 2.3 × 1013vg / kg, or 2.4 × 1013vg / kg, or 2.5 × 1013vg / kg, or 2.6 × 1013vg / kg, or 2.7 × 1013vg / kg, or 2.8 × 1013vg / kg, or 2.9 × 1013vg / kg, or 3.0 × 1013vg / kg, or 3.1 × 1013vg / kg, or 3.2 × 1013vg / kg, or 3.3 × 1013vg / kg, or 3.4 × 1013vg / kg, or 3.5 × 1013vg / kg, or 3.6 × 1013vg / kg, or 3.7 × 1013vg / kg, or 3.8 × 1013vg / kg, or 3.9 × 1013vg / kg, or 4.0 × 1013vg / kg, or 4.1 × 1013vg / kg, or 4.2 × 1013vg / kg, or 4.3 × 1013vg / kg, or 4.4 × 1013vg / kg, or 4.5 × 1013vg / kg, or 4.6 × 1013vg / kg, or 4.7 × 1013vg / kg, or 4.8 × 1013vg / kg, or 4.9 × 1013vg / kg, or 5.0 × 1013vg / kg, or 5.1 × 1013vg / kg, or 5.2 × 1013vg / kg, or 5.3 × 1013vg / kg, or 5.4 × 1013vg / kg, or 5.5 × 1013vg / kg, or 5.6 × 1013vg / kg, or 5.7 × 1013vg / kg, or 5.8 × 1013vg / kg, or 5.9 × 1013vg / kg, or 6.0 × 1013vg / kg, or 6.1 × 1013vg / kg, or 6.2 × 1013vg / kg, or 6.3 × 1013vg / kg, or 6.4 × 1013vg / kg, or 6.5 × 1013vg / kg, or 6.6 × 1013vg / kg, or 6.7 × 1013vg / kg, or 6.8 × 1013vg / kg, or 6.9 × 1013vg / kg, or 7.0 × 1013vg / kg, or 7.1 × 1013vg / kg, or 7.2 × 1013vg / kg, or 7.3 × 1013vg / kg, or 7.4 × 1013vg / kg, or 7.5 × 1013vg / kg, or 7.6 × 1013vg / kg, or 7.7 × 1013vg / kg, or 7.8 × 1013vg / kg, or 7.9 × 1013vg / kg, or 8.0 × 1013vg / kg, or 8.1 × 1013vg / kg, or 8.2 × 1013vg / kg, or 8.3 × 1013vg / kg, or 8.4 × 1013vg / kg, or 8.5 × 1013vg / kg, or 8.6 × 1013vg / kg, or 8.7 × 1013vg / kg, or 8.8 × 1013vg / kg, or 8.9 × 1013vg / kg, or 9.0 × 1013vg / kg, or 9.1 × 1013vg / kg, or 9.2 × 1013vg / kg, or 9.3 × 1013vg / kg, or 9.4 × 1013vg / kg, or 9.5 × 1013vg / kg, or 9.6 × 1013vg / kg, or 9.7 × 1013vg / kg, or 9.8 × 1013vg / kg, or 9.9 × 1013vg / kg, or 1.0 × 1014vg / kg.

5. The method for treating according to claim 1, wherein the recombinant viral vector AAV5- FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248-0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15- 0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml.

6. The method for treating according to claim 5, wherein the recombinant viral vector AAV5- FIX is administered in the form of a pharmaceutical composition comprising recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml.

7. The method for treating according to claim 1, wherein hemophilia B is mild hemophilia B, or moderate hemophilia B, or severe hemophilia B.

8. The method for treating according to claim 7, wherein hemophilia B is: (i) severe hemophilia B with FIX activity < 1 %; (ii) severe hemophilia B with FIX activity <1 IU / dl; (iii) moderate hemophilia B with FIX activity of 1-5 %; (iv) moderate hemophilia B with FIX activity of 1-5 IU / dl; (v) mild hemophilia B with FIX activity > 5%; (vi) mild hemophilia B with FIX activity of 5-40 IU / dl; (vii) hemophilia B without FIX inhibitor (inhibitor titer <0.6 BU); (viii) hemophilia B with FIX inhibitor (inhibitor titer ≥0.6 BU); (ix) hemophilia B with antibodies to AAV5; (x) hemophilia B with antibodies to AAV5 (antibody to AAV5 titer > 1:5); (xi) hemophilia B without antibodies to AAV5; or (xii) hemophilia B without antibodies to AAV5 (antibody to AAV5 titer < 1:5);9. The method for treating according to claim 1, wherein the recombinant viral vector AAV5- FIX comprises: 1) a nucleic acid that includes a nucleic acid with the nucleotide sequence of SEQ ID NO: 1 encoding the FIX (blood coagulation factor IX) protein; and 2) a capsid of the recombinant adeno-associated virus serotype 5.

10. The method for treating according to claim 9, wherein the nucleic acid includes the following elements in the 5'-end to 3'-end direction: a left-hand (first) ITR (inverted terminal repeats); TTR promoter (transthyretin promoter); an intron of the hBG1 gene (an intron-bearing fragment of the human β-globin gene); a nucleic acid encoding the FIX (blood coagulation factor IX) protein with the nucleotide sequence of SEQ ID NO: 1; an hGH1 polyadenylation signal (human growth hormone gene polyadenylation signal); a right-hand (second) ITR.

11. The method for treating according to claims 9-10, wherein the nucleic acid is represented by the nucleotide sequence of SEQ ID NO:

2.

12. The method for treating according to claim 9, wherein the capsid of the recombinant adeno- associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO:

5.

13. The method for treating according to claim 1, wherein the recombinant viral vector AAV5- FIX comprises: 1) a nucleic acid represented by the nucleotide sequence of SEQ ID NO: 2; 2) the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO:

5.

14. The method for treating according to claim 1, carried out by way of a single intravenous administration.

15. The method for treating according to claim 1, further comprising premedication, postmedication and / or concomitant therapy.

16. The method for treating according to claim 15, wherein the premedication, postmedication and / or concomitant therapy is the administration of an immunosuppressive agent and / or a human coagulation factor IX product.

17. The method for treating according to claim 16, wherein the immunosuppressive agent is selected from a glucocorticoid, a cytostatic, a calcineurin inhibitor, an mTOR inhibitor, a monoclonal antibody, or other immunosuppressant.

18. The method for treating according to claim 15, wherein premedication, postmedication and / or concomitant therapy is administered (i) daily prior to administration of the recombinant viral vector AAV5-FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX.

19. The use of recombinant viral vector AAV5-FIX at a dose of 1.0 × 1012vg / kg to 1.0 × 1014vg / kg for treating hemophilia B.

20. The use according to claim 19, wherein the dose is 1.0 × 1012vg / kg to 1.0 × 1014vg / kg, or 1.0 × 1012vg / kg to 9.9 × 1013vg / kg, 1.0 × 1012vg / kg to 9.8 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.7 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.6 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.5 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.4 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.3 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.2 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.1 × 1013vg / kg, or 1.0 × 1012vg / kg to 9.0 × 1013vg / kg, or 1.1 × 1012vg / kg to 8.9 × 1013vg / kg, or 1.2 × 1012vg / kg to 8.8 × 1013vg / kg, or 1.3 × 1012vg / kg to 8.7 × 1013vg / kg, or 1.4 × 1012vg / kg to 8.6 × 1013vg / kg, or 1.5 × 1012vg / kg to 8.5 × 1013vg / kg.

21. The use according to claim 20, wherein the dose is 1.0 × 1012vg / kg to 2.0 × 1012vg / kg, or 2.0 × 1012vg / kg to 3.0 × 1012vg / kg, or 2.3 × 1012vg / kg to 2.8 × 1012vg / kg, or 2.4 × 1012vg / kg to 2.6 × 1012vg / kg, or 3.0 × 1012vg / kg to 4.0 × 1012vg / kg, or 4.0 × 1012vg / kg to 5.0 × 1012vg / kg, or 4.5 × 1012vg / kg to 5.5 × 1012vg / kg, or 4.8 × 1012vg / kg to 5.3 × 1012vg / kg, or 4.9 × 1012vg / kg to 5.1 × 1012vg / kg, or 5.0 × 1012vg / kg to 6.0 × 1012vg / kg, or 6.0 × 1012vg / kg to 7.0 × 1012vg / kg, or 7.0 × 1012vg / kg to 8.0 × 1012vg / kg, or 8.0 × 1012vg / kg to 9.0 × 1012vg / kg, or 9.0 × 1012vg / kg to 1.0 × 1013vg / kg, or 1.0 × 1013vg / kg to 2.0 × 1013vg / kg, or 1.5 × 1013vg / kg to 2.5 × 1013vg / kg, or 1.8 × 1013vg / kg to 2.3 × 1013vg / kg, or 1.9 × 1013vg / kg to 2.1 × 1013vg / kg, or 2.0 × 1013vg / kg to 3.0 × 1013vg / kg, or 3.0 × 1013vg / kg to 4.0 × 1013vg / kg, or 4.0 × 1013vg / kg to 5.0 × 1013vg / kg, or 4.5 × 1013vg / kg to 5.5 × 1013vg / kg, or 4.8 × 1013vg / kg to 5.3 × 1013vg / kg, 1013vg / kg, or 4.9 × 1013vg / kg to 5.1 × 1013vg / kg, or 5.0 × 1013vg / kg to 6.0 × 1013vg / kg, or 6.0 × 1013vg / kg to 7.0 × 1013vg / kg, or 7.0 × 1013vg / kg to 8.0 × 1013vg / kg, or 8.0 × 1013vg / kg to 9.0 × 1013vg / kg, or 9.0 × 1013vg / kg to 1.0 × 1014vg / kg.

22. The use according to claim 21, wherein the dose is 1.0 × 1012vg / kg, or 1.1 × 1012vg / kg, or 1.2 × 1012vg / kg, or 1.3 × 1012vg / kg, or 1.4 × 1012vg / kg, or 1.5 × 1012vg / kg, or 1.6 × 1012vg / kg, or 1.7 × 1012vg / kg, or 1.8 × 1012vg / kg, or 1.9 × 1012vg / kg, or 2.0 × 1012vg / kg, or 2.1 × 1012vg / kg, or 2.2 × 1012vg / kg, or 2.3 × 1012vg / kg, or 2.4 × 1012vg / kg, or 2.5 × 1012vg / kg, or 2.6 × 1012vg / kg, or 2.7 × 1012vg / kg, or 2.8 × 1012vg / kg, or 2.9 × 1012vg / kg, or 3.0 × 1012vg / kg, or 3.1 × 1012vg / kg, or 3.2 × 1012vg / kg, or 3.3 × 1012vg / kg, or 3.4 × 1012vg / kg, or 3.5 × 1012vg / kg, or 3.6 × 1012vg / kg, or 3.7 × 1012vg / kg, or 3.8 × 1012vg / kg, or 3.9 × 1012vg / kg, or 4.0 × 1012vg / kg, or 4.1 × 1012vg / kg, or 4.2 × 1012vg / kg, or 4.3 × 1012vg / kg, or 4.4 × 1012vg / kg, or 4.5 × 1012vg / kg, or 4.6 × 1012vg / kg, or 4.7 × 1012vg / kg, or 4.8 × 1012vg / kg, or 4.9 × 1012vg / kg, or 5.0 × 1012vg / kg, or 5.1 × 1012vg / kg, or 5.2 × 1012vg / kg, or 5.3 × 1012vg / kg, or 5.4 × 1012vg / kg, or 5.5 × 1012vg / kg, or 5.6 × 1012vg / kg, or 5.7 × 1012vg / kg, or 5.8 × 1012vg / kg, or 5.9 × 1012vg / kg, or 6.0 × 1012vg / kg, or 6.1 × 1012vg / kg, or 6.2 × 1012vg / kg, or 6.3 × 1012vg / kg, or 6.4 × 1012vg / kg, or 6.5 × 1012vg / kg, or 6.6 × 1012vg / kg, or 6.7 × 1012vg / kg, or 6.8 × 1012vg / kg, or 6.9 × 1012vg / kg, or 7.0 × 1012vg / kg, or 7.1 × 1012vg / kg, or 7.2 × 1012vg / kg, or 7.3 × 1012vg / kg, or 7.4 × 1012vg / kg, or 7.5 × 1012vg / kg, or 7.6 × 1012vg / kg, or 7.7 × 1012vg / kg, or 7.8 × 1012vg / kg, or 7.9 × 1012vg / kg, or 8.0 × 1012vg / kg, or 8.1 × 1012vg / kg, or 8.2 × 1012vg / kg, or 8.3 × 1012vg / kg, or 8.4 × 1012vg / kg, or 8.5 × 1012vg / kg, or 8.6 × 1012vg / kg, or 8.7 × 1012vg / kg, or 8.8 × 1012vg / kg, or 8.9 × 1012vg / kg, or 9.0 × 1012vg / kg, or 9.1 × 1012vg / kg, or 9.2 × 1012vg / kg, or 9.3 × 1012vg / kg, or 9.4 × 1012vg / kg, or 9.5 × 1012vg / kg, or 9.6 × 1012vg / kg, or 9.7 × 1012vg / kg, or 9.8 × 1012vg / kg, or 9.9 × 1012vg / kg, or 1.0 × 1013vg / kg, or 1.1 × 1013vg / kg, or 1.2 × 1013vg / kg, or 1.3 × 1013vg / kg, or 1.4 × 1013vg / kg, or 1.5 × 1013vg / kg, or 1.6 × 1013vg / kg, or 1.7 × 1013vg / kg, or 1.8 × 1013vg / kg, or 1.9 × 1013vg / kg, or 2.0 × 1013vg / kg, or 2.1 × 1013vg / kg, or 2.2 × 1013vg / kg, or 2.3 × 1013vg / kg, or 2.4 × 1013vg / kg, or 2.5 × 1013vg / kg, or 2.6 × 1013vg / kg, or 2.7 × 1013vg / kg, or 2.8 × 1013vg / kg, or 2.9 × 1013vg / kg, or 3.0 × 1013vg / kg, or 3.1 × 1013vg / kg, or 3.2 × 1013vg / kg, or 3.3 × 1013vg / kg, or 3.4 × 1013vg / kg, or 3.5 × 1013vg / kg, or 3.6 × 1013vg / kg, or 3.7 × 1013vg / kg, or 3.8 × 1013vg / kg, or 3.9 × 1013vg / kg, or 4.0 × 1013vg / kg, or 4.1 × 1013vg / kg, or 4.2 × 1013vg / kg, or 4.3 × 1013vg / kg, or 4.4 × 1013vg / kg, or 4.5 × 1013vg / kg, or 4.6 × 1013vg / kg, or4.7 × 1013vg / kg, or 4.8 × 1013vg / kg, or 4.9 × 1013vg / kg, or 5.0 × 1013vg / kg, or 5.1 × 1013vg / kg, or 5.2 × 1013vg / kg, or 5.3 × 1013vg / kg, or 5.4 × 1013vg / kg, or 5.5 × 1013vg / kg, or 5.6 × 1013vg / kg, or 5.7 × 1013vg / kg, or 5.8 × 1013vg / kg, or 5.9 × 1013vg / kg, or 6.0 × 1013vg / kg, or 6.1 × 1013vg / kg, or 6.2 × 1013vg / kg, or 6.3 × 1013vg / kg, or 6.4 × 1013vg / kg, or 6.5 × 1013vg / kg, or 6.6 × 1013vg / kg, or 6.7 × 1013vg / kg, or 6.8 × 1013vg / kg, or 6.9 × 1013vg / kg, or 7.0 × 1013vg / kg, or 7.1 × 1013vg / kg, or 7.2 × 1013vg / kg, or 7.3 × 1013vg / kg, or 7.4 × 1013vg / kg, or 7.5 × 1013vg / kg, or 7.6 × 1013vg / kg, or 7.7 × 1013vg / kg, or 7.8 × 1013vg / kg, or 7.9 × 1013vg / kg, or 8.0 × 1013vg / kg, or 8.1 × 1013vg / kg, or 8.2 × 1013vg / kg, or 8.3 × 1013vg / kg, or 8.4 × 1013vg / kg, or 8.5 × 1013vg / kg, or 8.6 × 1013vg / kg, or 8.7 × 1013vg / kg, or 8.8 × 1013vg / kg, or 8.9 × 1013vg / kg, or 9.0 × 1013vg / kg, or 9.1 × 1013vg / kg, or 9.2 × 1013vg / kg, or 9.3 × 1013vg / kg, or 9.4 × 1013vg / kg, or 9.5 × 1013vg / kg, or 9.6 × 1013vg / kg, or 9.7 × 1013vg / kg, or 9.8 × 1013vg / kg, or 9.9 × 1013vg / kg, or 1.0 × 1014vg / kg.

23. The use according to claim 19, wherein the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising the recombinant viral vector AAV5-FIX, histidine in an amount of 2.0-3.58 mg, arginine in an amount of 0.248-0.448 mg, sodium chloride in an amount of 8.0-15.0 mg, magnesium chloride hexahydrate in an amount of 0.15-0.50 mg, Poloxamer 188 in an amount of 0.01-1.0 mg and water for injections ad 1 ml.

24. The use according to claim 23, wherein the recombinant viral vector AAV5-FIX is administered in the form of a pharmaceutical composition comprising recombinant viral vector AAV5-FIX – 5 x 1012vg; arginine – 0.35 mg, histidine – 2.79 mg, sodium chloride – 11.7 mg, Poloxamer 188 – 0.05 mg, magnesium chloride hexahydrate – 0.20 mg, water for injections – ad 1.0 ml.

25. The use according to claim 19, wherein hemophilia B is mild hemophilia B, or moderate hemophilia B, or severe hemophilia B.

26. The use according to claim 25, wherein hemophilia B is: (i) severe hemophilia B with FIX activity < 1 %; (ii) severe hemophilia B with FIX activity <1 IU / dl; (iii) moderate hemophilia B with FIX activity of 1-5 %; (iv) moderate hemophilia B with FIX activity of 1-5 IU / dl; (v) mild hemophilia B with FIX activity > 5%; (vi) mild hemophilia B with FIX activity of 5-40 IU / dl; (vii) hemophilia B without FIX inhibitor (inhibitor titer <0.6 BU); (viii) hemophilia B with FIX inhibitor (inhibitor titer ≥0.6 BU); (ix) hemophilia B with antibodies to AAV5; (x) hemophilia B with antibodies to AAV5 (antibody to AAV5 titer > 1:5); (xi) hemophilia B without antibodies to AAV5; or (xii) hemophilia B without antibodies to AAV5 (antibody to AAV5 titer < 1:5); 27. The use according to claim 19, wherein the recombinant viral vector AAV5-FIX comprises: 1) a nucleic acid that includes a nucleic acid with the nucleotide sequence of SEQ ID NO: 1 encoding the FIX (blood coagulation factor IX) protein; and 2) a capsid of the recombinant adeno-associated virus serotype 5.

28. The use according to claim 27, wherein the nucleic acid includes the following elements in the 5'-end to 3'-end direction: a left-hand (first) ITR (inverted terminal repeats); TTR promoter (transthyretin promoter);an intron of the hBG1 gene (an intron-bearing fragment of the human β-globin gene); a nucleic acid encoding the FIX (blood coagulation factor IX) protein with the nucleotide sequence of SEQ ID NO: 1; an hGH1 polyadenylation signal (human growth hormone gene polyadenylation signal); a right-hand (second) ITR.

29. The use according to claims 27-28, wherein the nucleic acid is represented by the nucleotide sequence of SEQ ID NO:

2.

30. The use according to claim 27, wherein the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO:

5.

31. The use according to claim 19, wherein the recombinant viral vector AAV5-FIX comprises: 1) a nucleic acid represented by the nucleotide sequence of SEQ ID NO: 2; 2) the capsid of the recombinant adeno-associated virus serotype 5 comprises the AAV5 protein VP1 with the amino acid sequence of SEQ ID NO: 3, the AAV5 protein VP2 with the amino acid sequence of SEQ ID NO: 4, and the AAV5 protein VP3 with the amino acid sequence of SEQ ID NO:

5.

32. The use according to claim 19, carried out by way of a single intravenous administration.

33. The use according to claim 19, further comprising premedication, postmedication and / or concomitant therapy.

34. The use according to claim 33, wherein the premedication, postmedication and / or concomitant therapy is the administration of an immunosuppressive agent and / or a human coagulation factor IX product.

35. The use according to claim 34, wherein the immunosuppressive agent is selected from a glucocorticoid, an antimetabolite, a calcineurin inhibitor, an mTOR inhibitor, a monoclonal antibody, or other immunosuppressant.

36. The use according to claim 19, wherein premedication, postmedication and / or concomitant therapy is administered (i) daily prior to administration of the recombinant viral vector AAV5-FIX, and / or (ii) on the day of administration of the recombinant viral vector AAV5-FIX, and / or (iii) daily post administration of the recombinant viral vector AAV5-FIX.

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