Antibodies specifically recognizing nogo-a and uses thereof

Abstract

Antibodies or antigen-binding fragments that specifically recognize Nogo-A, methods of making and uses thereof.

Description

[0001] Cross-reference of related applications

[0002] This application claims priority to Chinese Patent Application No. 202211006418.4, filed on August 22, 2022, entitled "Antibody that specifically recognizes Nogo-A and its application", the entire contents of which are incorporated herein by reference.

[0003] Submit the electronic sequence list as an XML file

[0004] The contents of the electronic sequence list are incorporated into this document by reference in their entirety: (NOGOA_WIPO_2023.08.17.xml; size: 153KB; and creation date: 2022.08.03). Technical Field

[0005] This invention relates to antibodies that specifically recognize NogoA, their preparation methods and uses, including methods for treating diseases and / or conditions caused by Nogo-A signaling pathway dysregulation, such as diseases or injuries of the central nervous system and / or peripheral nervous system. Background Technology

[0006] Following injury to the adult central nervous system (CNS), neurogenesis is limited due to the presence of an inhibitory myelin environment covering axons and the formation of scar tissue. Previous studies have shown that factors inhibiting neurogenesis significantly influence the regenerative capacity of the adult CNS after injury. These factors play crucial roles in stabilizing the complex wiring of the adult higher vertebrate CNS and in establishing neuronal pathways during nervous system development (Akbik FV et al. Exp Neurol. 2012.; Schwab ME et al. Nat Rev Neurosci. 2010.), including molecules such as Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte glycoprotein (OMGP), which have been described as effective inhibitors of neurite outgrowth.

[0007] One of the most studied inhibitory factors is Nogo-A, a member of the plasma membrane protein family. It occurs in myelin and certain neurons, inhibiting axonal regeneration and plasticity following central nervous system injury (Filbin et al. Nat Rev Neurosci. 2003; Yiu G et al. Nat Rev Neurosci. 2006). Nogo-A exerts its inhibitory activity through two distinct extracellular domains, Nogo-A-Δ20 (mouse aa544-725) and Nogo-66 (mouse aa1026-1091) (Schwab ME et al., Nat Rev Neurosci). Anissa Kempf et al. discovered that the G protein-coupled receptor (GPCR) sphingosine 1-phosphate receptor 2 (S1PR2) is the functional receptor for the Δ20 domain of Nogo-A (Kempf A et al. PLoS Biol. 2014.).

[0008] Nogo-A binds to the receptor NgR1 via its inhibitory Nogo-66 domain and forms a complex with transmembrane proteins LINGO1, p75, or TROY, thereby inhibiting neurite growth. This binding leads to intracellular calcium loss through an unknown intermediate. 2+ Increased levels of NgR1 and activation of the Rho-associated protein kinase (ROCK) signaling pathway (Nash M et al., Mol Neurobiol, 2009; Fournier AE et al., J. Neurosci. 2003). Through RhoA signaling, the actin cytoskeleton becomes unstable, leading to growth cone collapse (Hsieh et al., J. Neurosci, 2006; Montani, L et al., J. Biol. Chem. 2009). In addition to NgR1, Nogo-66 also interacts with accessory proteins and paired immunoglobulin-like receptor B (PIRB) (Atwal JK et al., Science. 2008), inducing growth inhibition.

[0009] Nogo-A is primarily expressed in the nervous system, exhibiting three distinct expression windows during development (Huber et al., Trends Cell Biol, 2007; Wang, X et al., J. Neurosci. 2002.). First, in early development, Nogo-A is expressed in migrating neuroblasts and immature neurons in the neural tube (Caltharp et al., BMC Dev Biol, 2007; Mathis et al., Cereb Cortex, 2010.). Second, during the major growth phases of central and peripheral neurons, Nogo-A is expressed in various neuronal types, particularly neurons with long axons. This expression declines to generally undetectable low levels after birth. However, some neuronal types retain high levels of Nogo-A expression, particularly in the olfactory bulb, pyramidal cells and interneurons of the hippocampus, spinal motor neurons, and dorsal root ganglion cells (Mingorance, A et al., Mol Cell Neurosci, 2004; Richard, M et al., Europ. J. Neurosci, 2005.). These neuronal types are characterized by highly plastic connections, suggesting that neuronal Nogo may play a role in synaptic plasticity. Finally, in the postnatal central nervous system, Nogo-A is primarily expressed in oligodendrocytes. However, cell-like types in the peripheral nervous system (Schwann cells) do not express Nogo-A (Huber et al., J. Neurosci, 2002). Outside the central nervous system, Nogo-A is expressed in developing skin, differentiating skeletal muscle, and the heart. Heart tissues from adult rats, mice, and humans, as well as certain immune cells, particularly macrophages, in mice and humans, express Nogo-A and components of the Nogo receptor complex such as NgR1.

[0010] In Nogo-A deficient mice, the inhibitory effect of spinal cord extracts on neurite growth was reduced in these mice. Two weeks after dorsal resection of the thoracic spinal cord in adult mice, Nogo-A KO mice showed more corticospinal tract (CST) fibers growing towards the lesion site compared to wild-type mice. This study demonstrates that systemic deficiency of the myelin-associated growth inhibitor Nogo-A can improve regenerative and plastic responses following spinal cord injury (M Simonen et al., Neuron, 2003). Furthermore, neutralization of Nogo-A has been shown to promote axonal growth and compensatory germination in the adult spinal cord and brain, and to improve functional recovery after central nervous system injury (Schwab ME et al. Curr Opin Neurobiol. 2004.; Kempf et al. Physiology. 2013.). Recent studies have shown that Nogo-A signaling plays a new and important role in inhibiting synaptic plasticity in mature neuronal networks, indicating that Nogo-A's inhibitory potential far exceeds its previously studied limitation on axonal growth (Kempf A et al. PLoS Biol. 2014.; Delekate et al. Proc Natl Acad Sci. 2011.; Tews B et al. Proc Natl Acad Sci. 2013.). In addition to its inhibitory effect on axonal regeneration in the adult central nervous system, researchers have also found that Nogo-A regulates the migration of neural progenitors in the mouse embryonic cortex. Enhanced migration of cortical neural progenitors was observed in Nogo-A- / - mice and in wild-type neurons cultured with anti-Nogo-A, NgR1, or LINGO-1 antibodies, suggesting that cell-surface Nogo-A regulates neuronal migration in the early developing CNS through NgR1-LINGO1 receptor complexes (Mathis, C et al., Cereb Cortex, 2010).

[0011] Patent application WO2004052932A2 discloses a monoclonal antibody or fragment thereof that binds to a human Nogo-A peptide, and the use of these antibodies to treat diseases related to nerve repair, etc. WO2009056509A1 discloses a monoclonal antibody or fragment thereof that binds to a human Nogo-A peptide, and the use of such binding molecules as pharmaceuticals, particularly in the treatment of peripheral and / or central nervous system diseases.

[0012] Therefore, there is still a need in the field for therapeutic antibodies that can effectively inhibit or otherwise antagonize Nogo-A, as well as related methods for treating Nogo-A-mediated diseases or conditions, such as central nervous system injury and / or repair, spinal cord injury, Alzheimer's disease, and other diseases.

[0013] All publications, patents, patent applications, and disclosed information in published patent applications mentioned herein are incorporated herein by reference in their entirety.

[0014] Application Overview

[0015] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising a heavy chain variable domain (V... H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYGMH (SEQ ID NO:1); HC-CDR2, which contains SISHTGKTVFYGESVKG (SEQ ID NO:3); and HC-CDR3, which contains TELGGDNWFDV (SEQ ID NO:5); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains TGSSSNIGGYDVY (SEQ ID NO:7); LC-CDR2, which contains DNNKRPS (SEQ ID NO:9); and LC-CDR3, which contains AAWDDSLYGYI (SEQ ID NO:11).

[0016] In some embodiments, an isolated anti-Nogo-A antibody is provided, which comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant containing substitutions of up to about 3 amino acids; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, the variant containing substitutions of up to about 3 amino acids; and HC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, the variant containing substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:7 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:11 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids.

[0017] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: V H The V HV containing any of the amino acid sequences shown in SEQ ID NOs:13-16 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:18-19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0018] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:13. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:18. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:14. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:15. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:16. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0019] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:3; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:5, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:7; LC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:11, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0020] In some embodiments, any isolated anti-Nogo-A antibody as described above comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:13-16 or variants thereof, wherein the variants have at least about 80% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-16; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:18-19 or variants thereof, wherein the variants have at least about 80% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:18-19.

[0021] In some embodiments, a separated anti-Nogo-A antibody comprises: (i) V H It comprises the amino acid sequence SEQ ID NO:13 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:13; and V L It contains the amino acid sequence SEQ ID NO:18 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:18; (ii) V H It comprises the amino acid sequence SEQ ID NO:14 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:14; and V L It contains the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19; (iii) V HIt comprises the amino acid sequence SEQ ID NO:15 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:15; and V L It contains the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19; (iv) V H It comprises the amino acid sequence SEQ ID NO:16 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:16; and V L It contains the amino acid sequence SEQ ID NO:19 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19.

[0022] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:17. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:20. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0023] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:4; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:6, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:8; LC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:12, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0024] In some embodiments, any isolated anti-Nogo-A antibody as described above comprises: V HIt comprises the amino acid sequence shown in SEQ ID NO:17 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:17; and V L It contains the amino acid sequence shown in SEQ ID NO:20 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:20.

[0025] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising a heavy chain variable domain (V... H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SYGMH (SEQ ID NO:28); HC-CDR2, which contains VIWYHGSKKYYADSVKD (SEQ ID NO:48); and HC-CDR3, which contains SIAETTDYGLDS (SEQ ID NO:65); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLYRGGKTFLY (SEQ ID NO:85); LC-CDR2, which includes ELSNRAS (SEQ ID NO:100); and LC-CDR3, which includes MQGIQLPWT (SEQ ID NO:111).

[0026] In some embodiments, an isolated anti-Nogo-A antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:28 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in SEQ ID NO:48 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in SEQ ID NO:65 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:85 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:100 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:111 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids.

[0027] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:127-128 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:150-151 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0028] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:127. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:150. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:128. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:151. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:128. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:150. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0029] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:28; HC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:65, or the VH Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:85; LC-CDR2, which contains the amino acid sequence SEQ ID NO:100; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:111, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0030] In some embodiments, any isolated anti-Nogo-A antibody as described above comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:127-128 or variants thereof, wherein the variants have at least about 80% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:127-128; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:150-151 or variants thereof, wherein the variants have at least about 80% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:150-151.

[0031] In some embodiments, a separated anti-Nogo-A antibody comprises: (i) V H It comprises the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:127; and V L It contains the amino acid sequence SEQ ID NO:150 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:150; (ii) V H It comprises the amino acid sequence SEQ ID NO:128 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:128; and V L It contains the amino acid sequence SEQ ID NO:151 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:151; (iii) V H It comprises the amino acid sequence SEQ ID NO:128 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:128; and V LIt contains the amino acid sequence SEQ ID NO:150 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:150.

[0032] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:129. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:152. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0033] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:29; HC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:66, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:86; LC-CDR2, which contains the amino acid sequence SEQ ID NO:101; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:112, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0034] In some embodiments, any isolated anti-Nogo-A antibody as described above comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:129 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:129; and V L It contains the amino acid sequence shown in SEQ ID NO:152 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:152.

[0035] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V HIt contains V as shown in the amino acid sequence SEQ ID NO:130. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:153. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0036] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:30; HC-CDR2, which contains the amino acid sequence SEQ ID NO:50; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:87; LC-CDR2, which contains the amino acid sequence SEQ ID NO:102; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:113, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0037] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:130 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:130; and V L It contains the amino acid sequence SEQ ID NO:153 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:153.

[0038] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:131. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:154. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0039] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:68, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0040] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:131 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:131; and V L It contains the amino acid sequence SEQ ID NO:154 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:154.

[0041] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:132. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:155. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0042] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:32; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:69, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0043] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:132 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:132; and V L It contains the amino acid sequence SEQ ID NO:155 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:155.

[0044] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:133. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:156. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0045] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:33; HC-CDR2, which contains the amino acid sequence SEQ ID NO:52; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:70, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:89; LC-CDR2, which contains the amino acid sequence SEQ ID NO:104; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:115, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0046] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:133 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:133; and V L It contains the amino acid sequence SEQ ID NO:156 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:156.

[0047] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:134. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:157. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0048] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:34; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:71, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0049] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:134 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:134; and V L It contains the amino acid sequence SEQ ID NO:157 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:157.

[0050] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:135. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:158. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0051] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:35; HC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:72, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:90; LC-CDR2, which contains the amino acid sequence SEQ ID NO:105; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:116, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0052] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:135 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:135; and V LIt contains the amino acid sequence SEQ ID NO:158 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:158.

[0053] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:136. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:159. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0054] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:36; HC-CDR2, which contains the amino acid sequence SEQ ID NO:55; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:73, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91; LC-CDR2, which contains the amino acid sequence SEQ ID NO:106; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0055] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:136 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:136; and V L It contains the amino acid sequence SEQ ID NO:159 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:159.

[0056] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:137.H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:159. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0057] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:37; HC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:74, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91; LC-CDR2, which contains the amino acid sequence SEQ ID NO:106; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0058] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:137 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:137; and V L It contains the amino acid sequence SEQ ID NO:159 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:159.

[0059] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:138. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:160. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0060] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:57; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:75, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:92; LC-CDR2, which contains the amino acid sequence SEQ ID NO:107; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:118, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0061] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:138 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:138; and V L It contains the amino acid sequence SEQ ID NO:160 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:160.

[0062] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:139. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:161. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0063] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:38; HC-CDR2, which contains the amino acid sequence SEQ ID NO:58; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:76, or the VH Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:93; LC-CDR2, which contains the amino acid sequence SEQ ID NO:108; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:119, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0064] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:139 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:139; and V L It contains the amino acid sequence SEQ ID NO:161 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:161.

[0065] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:140. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:162. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0066] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:39; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:77, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0067] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:140 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:140; and V L It contains the amino acid sequence SEQ ID NO:162 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:162.

[0068] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:141. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:163. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0069] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:40; HC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:78, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:94; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:121, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0070] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:141 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:141; and V L It contains the amino acid sequence SEQ ID NO:163 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:163.

[0071] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:142. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:164. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0072] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:41; HC-CDR2, which contains the amino acid sequence SEQ ID NO:60; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:79, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0073] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:142 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:142; and V LIt contains the amino acid sequence SEQ ID NO:164 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:164.

[0074] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:143. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:165. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0075] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:42; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0076] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:143 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:143; and V L It contains the amino acid sequence SEQ ID NO:165 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:165.

[0077] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:144.H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:166. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0078] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95; LC-CDR2, which contains the amino acid sequence SEQ ID NO:109; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:122, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0079] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:144; and V L It contains the amino acid sequence SEQ ID NO:166 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:166.

[0080] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:167. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0081] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:44; HC-CDR2, which contains the amino acid sequence SEQ ID NO:62; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:82, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:96; LC-CDR2, which contains the amino acid sequence SEQ ID NO:110; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:123, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0082] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:145; and V L It contains the amino acid sequence SEQ ID NO:167 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:167.

[0083] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:146. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:168. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0084] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:45; HC-CDR2, which contains the amino acid sequence SEQ ID NO:63; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:83, or the VH Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:97; LC-CDR2, which contains the amino acid sequence SEQ ID NO:104; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:124, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0085] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:146 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:146; and V L It contains the amino acid sequence SEQ ID NO:168 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:168.

[0086] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:147. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:169. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0087] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:46; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:98; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0088] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:147 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:147; and V L It contains the amino acid sequence SEQ ID NO:169 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:169.

[0089] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:148. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:170. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0090] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:47; HC-CDR2, which contains the amino acid sequence SEQ ID NO:64; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:84, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:99; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:125, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0091] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:148 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:148; and V L It contains the amino acid sequence SEQ ID NO:170 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:170.

[0092] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:149. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:171. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0093] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95; LC-CDR2, which contains the amino acid sequence SEQ ID NO:109; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:126, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0094] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H It comprises the amino acid sequence SEQ ID NO:149 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:149; and V LIt contains the amino acid sequence SEQ ID NO:171 or a variant thereof, the variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:171.

[0095] In some embodiments, the Kd value of the isolated anti-Nogo-A antibody binding to human Nogo-A is from 0.1 pM to about 10 nM.

[0096] In some embodiments, an isolated anti-Nogo-A antibody is provided that competes with any of the isolated anti-Nogo-A antibodies described above for specific binding to Nogo-A. In some embodiments, an isolated anti-Nogo-A antibody is provided that specifically binds to the same epitope as any of the isolated anti-Nogo-A antibodies described above.

[0097] In some embodiments, the isolated anti-Nogo-A antibody, as described above, comprises an Fc fragment. In some embodiments, the isolated anti-Nogo-A antibody is a full-length IgG antibody. In some embodiments, the isolated anti-Nogo-A antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-Nogo-A antibody is a chimeric, fully human, or humanized antibody. In some embodiments, the isolated anti-Nogo-A antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.

[0098] In some embodiments, an isolated nucleic acid molecule is provided, the nucleic acid molecule encoding any of the anti-Nogo-A antibodies described above. In some embodiments, a vector is provided, the vector comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, the host cell comprising any of the anti-Nogo-A antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for preparing an anti-Nogo-A antibody is provided, comprising: a) culturing any of the above-described host cells under conditions that enable efficient expression of anti-Nogo-A antibodies; and b) obtaining the expressed anti-Nogo-A antibody from the host cell.

[0099] In some embodiments, a method of treating a desired individual disease or condition is provided, comprising administering to the individual an effective amount of any of the anti-Nogo-A antibodies described above. In some embodiments, the use of any of the anti-Nogo-A antibodies described above in the preparation of a pharmaceutical composition for treating a desired individual disease or condition is provided. In some embodiments, the use of any of the anti-Nogo-A antibodies described above or a pharmaceutical composition comprising an anti-Nogo-A antibody in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is related to the Nogo-A signaling pathway, including diseases or injuries or conditions of the central nervous system and / or peripheral nervous system. In some embodiments, the disease or condition is selected from, for example, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Lewy body-like disease, other common dementias, post-traumatic brain, brain, or spinal cord injury, stroke, demyelinating diseases such as multiple sclerosis, monophasic demyelinating disease, encephalomyelitis, multifocal leukoencephalitis, panencephalitis, Marchiafava-Bignami disease, pontine myelmolysis, adrenocortical leukodystrophy, Perizoise-Metzbach disease, spongiform encephalopathy, and subacute encephalopathy. Alexander's disease, leukodermal spongiform degeneration, metachromatic leukodystrophy, and Crawford's disease; degenerative visual disorders such as general ischemic retinopathy, anterior ischemic optic neuropathy, optic neuritis, age-related macular degeneration, diabetic retinopathy, cystic macular edema (CME), retinitis pigmentosa, Skoda's disease, Best's yolk sac degeneration, Leber's congenital amaurosis and other hereditary retinal degenerations, pathological myopia, precocious retinopathy, and Leber's hereditary optic neuropathy; and mental illnesses such as schizophrenia and depression.

[0100] It also provides pharmaceutical compositions, kits, and manufactured products containing any of the anti-Nogo-A antibodies described above. Attached Figure Description

[0101] Figure 1 shows the binding affinity of anti-Nogo-A antibody to hNiG as analyzed by ELISA. Figure 1A The figure shows the binding affinity of the exemplary antibody mkNG-22 to hNiG as analyzed by ELISA. Figure 1B The binding affinity of exemplary antibodies L82, H-L82-1, H-L82-2, and H-L82-3 to hNiG, as analyzed by ELISA, is shown.

[0102] Figure 2 shows the inhibitory activity of anti-Nogo-A antibody against hNiG and the binding of Nogo-A receptor on the cell membrane surface, as analyzed by ELISA. Figure 2AThe images show the inhibitory activity of exemplary antibodies L82, H-L82-1, H-L82-2, and H-L82-3 on the binding of Nogo-A receptors on the cell membranes of hNiG and PC12 cells, as analyzed by ELISA. Figure 2B The images show the inhibitory activity of exemplary antibodies L82, H-L82-1, H-L82-2, and H-L82-3 on the binding of Nogo-A receptors on the cell membranes of hNiG and 3T3 cells, as analyzed by ELISA.

[0103] Figure 3 shows the cross-binding activity of anti-Nogo-A antibodies with Nogo-A from different species, including humans, rhesus monkeys, rats, and mice, as analyzed by FACS. Figure 3A The figure shows the binding activity of anti-Nogo-A antibodies mkNG-22, L82, H-L82-1, H-L82-2 and H-L82-3 to human Nogo-A as analyzed by FACS. Figure 3B The figure shows the cross-binding activity of anti-Nogo-A antibodies mkNG-22, L82, H-L82-1, H-L82-2 and H-L82-3 with rhesus monkey Nogo-A as analyzed by FACS. Figure 3C The figure shows the cross-binding activity of anti-Nogo-A antibodies mkNG-22, L82, H-L82-1, H-L82-2 and H-L82-3 with rat Nogo-A as analyzed by FACS. Figure 3D The figure shows the cross-binding activity of anti-Nogo-A antibodies mkNG-22, L82, H-L82-1, H-L82-2 and H-L82-3 with mouse Nogo-A as analyzed by FACS.

[0104] Figure 4 The image shows the blocking activity of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3 and mkNG-22 against the transcriptional inhibition of GAP-43 by Nogo-A, as analyzed by relative quantitative real-time PCR.

[0105] Figure 5 shows the restorative effect of anti-Nogo-A antibody on the inhibition of neurite growth in N1E-115 cells by hNiG. Figure 5A The image shows the microscopic observation of the effects of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3 and mkNG-22 on the restoration of neurite growth morphology in N1E-115 cells inhibited by hNiG. Figure 5B The figure shows the quantitative analysis of the effects of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3 and mkNG-22 on the restoration of the proportion of neurite growth in N1E-115 cells inhibited by hNiG. Figure 5CThe figure shows the quantitative analysis of the effect of anti-Nogo-A antibody mkNG-362 on the restoration of the proportion of neurite growth in N1E-115 cells inhibited by hNiG.

[0106] Figure 6 shows the restorative effect of anti-Nogo-A antibody on the inhibition of neurite growth in N1E-115 cells by monkey spinal cord extract. Figure 6A The image shows the microscopic observation of the effects of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3, and mkNG-22 on the inhibition of neurite growth morphology restoration in monkey spinal cord extract. Figure 6B The figure shows the quantitative analysis of the effects of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3 and mkNG-22 on the restoration of the morphological ratio of N1E-115 cells inhibited by monkey spinal cord extract. Figure 6C The figure shows the exemplary effect of quantitative analysis of anti-Nogo-A antibodies mkNG-360 and mkNG-362 on the restoration of the proportion of PC12 cells inhibited by hNiG neurite growth.

[0107] Figure 7 The example shown illustrates the therapeutic effect of anti-Nogo-A antibody H-L82-3 on spinal cord injury in a mouse model of spinal cord injury.

[0108] Detailed description of this application

[0109] This application provides an anti-Nogo-A antibody molecule. Through a combination of scFv antibody yeast library screening, scFv phage library screening, CHO-IgG antibody display library screening, humanization, affinity maturation, and appropriately designed biochemical and biological experiments, a highly efficient antibody molecule capable of binding to human Nogo-A and inhibiting the interaction between human Nogo-A and its receptor has been identified. The results presented herein demonstrate that the antibody in this application binds to Nogo-A more effectively than known anti-Nogo-A antibodies ATI-355 or 11C7 (Novartis), and surprisingly, various biological experiments have shown that the antibody in this application is even more effective than ATI-355.

[0110] The anti-Nogo-A antibodies provided in this application include, for example, full-length anti-Nogo-A antibodies, anti-Nogo-A single-chain antibodies (scFvs), anti-Nogo-A Fc fusion proteins, multispecific (e.g., bispecific) anti-Nogo-A antibodies, anti-Nogo-A immunoconjugates, and the like.

[0111] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V HIt includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYGMH (SEQ ID NO:1); HC-CDR2, which contains SISHTGKTVFYGESVKG (SEQ ID NO:3); and HC-CDR3, which contains TELGGDNWFDV (SEQ ID NO:5); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains TGSSSNIGGYDVY (SEQ ID NO:7); LC-CDR2, which contains DNNKRPS (SEQ ID NO:9); and LC-CDR3, which contains AAWDDSLYGYI (SEQ ID NO:11).

[0112] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SHGMN (SEQ ID NO:2); HC-CDR2, which contains YISNGGDSTYYADSVKG (SEQ ID NO:4); and HC-CDR3, which contains TFSH (SEQ ID NO:6); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLHSNGNTYLH (SEQ ID NO:8); LC-CDR2, which includes GGSNRAS (SEQ ID NO:10); and LC-CDR3, which includes VQAIAFPYS (SEQ ID NO:12).

[0113] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SYGMH (SEQ ID NO:28); HC-CDR2, which contains VIWYHGSKKYYADSVKD (SEQ ID NO:48); and HC-CDR3, which contains SIAETTDYGLDS (SEQ ID NO:65); and light chain variable domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLYRGGKTFLY (SEQ ID NO:85); LC-CDR2, which includes ELSNRAS (SEQ ID NO:100); and LC-CDR3, which includes MQGIQLPWT (SEQ ID NO:111).

[0114] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DHYMD (SEQ ID NO:29); HC-CDR2, which contains FIRNKAKGGTTEYAASVKG (SEQ ID NO:49); and HC-CDR3, which contains LYGAYY (SEQ ID NO:66); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSISGWLA (SEQ ID NO: 86); LC-CDR2, which includes KASSLQS (SEQ ID NO: 101); and LC-CDR3, which includes QQYNSAPPT (SEQ ID NO: 112).

[0115] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYAMS (SEQ ID NO:30); HC-CDR2, which contains YIRTKSHNSAAEYAASVKG (SEQ ID NO:50); and HC-CDR3, which contains VGGY (SEQ ID NO:67); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLHSNGNTYLS (SEQ ID NO:87); LC-CDR2, which includes QVSNRYS (SEQ ID NO:102); and LC-CDR3, which includes GQGAHFPFT (SEQ ID NO:113).

[0116] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V HIt includes: heavy chain complementarity determination region (HC-CDR)1, which contains DYYMQ (SEQ ID NO:31); HC-CDR2, which contains RINPKTGGTNYAQKFQG (SEQ ID NO:51); and HC-CDR3, which contains GSAAVRD (SEQ ID NO:68); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR2, which contains WASTRES (SEQ ID NO:103); and LC-CDR3, which contains QQYYSTPLT (SEQ ID NO:114).

[0117] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains NYYIQ (SEQ ID NO:32); HC-CDR2, which contains RINPKTGGTNYAQKFQG (SEQ ID NO:51); and HC-CDR3, which contains GAAAAY (SEQ ID NO:69); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR2, which contains WASTRES (SEQ ID NO:103); and LC-CDR3, which contains QQYYSTPLT (SEQ ID NO:114).

[0118] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains NYDIH (SEQ ID NO:33); HC-CDR2, which contains LVRNKANTYTTEYAAAVKG (SEQ ID NO:52); and HC-CDR3, which contains PGTYSGSLDV (SEQ ID NO:70); and light chain variable domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGIINYLA (SEQ ID NO:89); LC-CDR2, which includes KASTLQS (SEQ ID NO:104); and LC-CDR3, which includes QQHNSYPLT (SEQ ID NO:115).

[0119] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYYIQ (SEQ ID NO:34); HC-CDR2, which contains RINPRTGGTNYAQKFQG (SEQ ID NO:53); and HC-CDR3, which contains GAAAVSY (SEQ ID NO:71); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR2, which contains WASTRES (SEQ ID NO:103); and LC-CDR3, which contains QQYYSTPLT (SEQ ID NO:114).

[0120] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains GSAMH (SEQ ID NO:35); HC-CDR2, which contains RIRSKSNNYATEYAASVKG (SEQ ID NO:54); and HC-CDR3, which contains GKIGTTPKFGSY (SEQ ID NO:72); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASESVSVFGINLIY (SEQ ID NO:90); LC-CDR2, which includes QASNKDT (SEQ ID NO:105); and LC-CDR3, which includes LQSKNSPLT (SEQ ID NO:116).

[0121] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V HIt includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SHGMN (SEQ ID NO:36); HC-CDR2, which contains YISNGGDSTYYADSVKG (SEQ ID NO:55); and HC-CDR3, which contains TFSH (SEQ ID NO:73); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLHSNGNTYLH (SEQ ID NO:91); LC-CDR2, which includes GGSNRAS (SEQ ID NO:106); and LC-CDR3, which includes VQAIAFPRT (SEQ ID NO:117).

[0122] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SYTMH (SEQ ID NO:37); HC-CDR2, which contains TIHSGGDTTYYTDSVKG (SEQ ID NO:56); and HC-CDR3, which contains SDV (SEQ ID NO:74); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLHSNGNTYLH (SEQ ID NO:91); LC-CDR2, which includes GGSNRAS (SEQ ID NO:106); and LC-CDR3, which includes VQAIAFPRT (SEQ ID NO:117).

[0123] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity determination region (HC-CDR)1, which contains DYYMQ (SEQ ID NO:31); HC-CDR2, which contains FIRNKPNGGTAEYAASVKG (SEQ ID NO:57); and HC-CDR3, which contains ADYYGSGLLFNY (SEQ ID NO:75); and light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLDSEDGNTYLE (SEQ ID NO:92); LC-CDR2, which includes EVSNRAS (SEQ ID NO:107); and LC-CDR3, which includes LQSLEYPFT (SEQ ID NO:118).

[0124] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYAMT (SEQ ID NO:38); HC-CDR2, which contains YIRSKSNNYATVYAASVKG (SEQ ID NO:58); and HC-CDR3, which contains GLTATN (SEQ ID NO:76); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which contains KSSQSLLYNSNNKNYLA (SEQ ID NO:93); LC-CDR2, which contains WASTRGS (SEQ ID NO:108); and LC-CDR3, which contains QQYYGPPLT (SEQ ID NO:119).

[0125] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains HYYIQ (SEQ ID NO:39); HC-CDR2, which contains RINPKTGGTNYAQKFQG (SEQ ID NO:51); and HC-CDR3, which contains GPAAISD (SEQ ID NO:77); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR2, which includes WASTRES (SEQ ID NO:103); and LC-CDR3, which includes HQYYSTPLT (SEQ ID NO:120).

[0126] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V HIt includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYYVQ (SEQ ID NO:40); HC-CDR2, which contains RINPRTGGTNYAQKFRG (SEQ ID NO:59); and HC-CDR3, which contains GPAAVAY (SEQ ID NO:78); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes KSSQNLLYSSNNKNYLA (SEQ ID NO:94); LC-CDR2, which includes WASTRES (SEQ ID NO:103); and LC-CDR3, which includes QQFYSTPLT (SEQ ID NO:121).

[0127] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes a heavy chain complementarity-determining region (HC-CDR) 1, which contains SYYIQ (SEQ ID NO:41); HC-CDR 2, which contains RINPKTGGTNFAQKFQG (SEQ ID NO:60); and HC-CDR 3, which contains GVAAASY (SEQ ID NO:79); and a light chain variable domain (V L ), the V L It includes a light chain complementarity determination region (LC-CDR) 1, which contains KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR 2, which contains WASTRES (SEQ ID NO:103); and LC-CDR 3, which contains QQYYSTPLT (SEQ ID NO:114).

[0128] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains AYYIQ (SEQ ID NO:42); HC-CDR2, which contains RINPKTGGTNYAQKFQG (SEQ ID NO:51); and HC-CDR3, which contains GAAAVNY (SEQ ID NO:80); and light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes KSSQSLLYSSNNKNYLA (SEQ ID NO:88); LC-CDR2, which includes WASTRES (SEQ ID NO:103); and LC-CDR3, which includes HQYYSTPLT (SEQ ID NO:120).

[0129] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYYLQ (SEQ ID NO:43); HC-CDR2, which contains RINPKTGATNYTQKFQG (SEQ ID NO:61); and HC-CDR3, which contains VVY (SEQ ID NO:81); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGITNDLL (SEQ ID NO:95); LC-CDR2, which includes EASSLQG (SEQ ID NO:109); and LC-CDR3, which includes QQYKGAPYS (SEQ ID NO:122).

[0130] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity determination region (HC-CDR)1, which contains TYWWG (SEQ ID NO:44); HC-CDR2, which contains EINTNSGSTSYNPSLKS (SEQ ID NO:62); and HC-CDR3, which contains AAAYYYALDS (SEQ ID NO:82); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQNVSSWLA (SEQ ID NO: 96); LC-CDR2, which includes KTSSLRS (SEQ ID NO: 110); and LC-CDR3, which includes QQYNCAPLT (SEQ ID NO: 123).

[0131] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V HIt includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DSYMH (SEQ ID NO:45); HC-CDR2, which contains LVRNKDKSYTTEYAAAVKG (SEQ ID NO:63); and HC-CDR3, which contains FNH (SEQ ID NO:83); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQDISIWLA (SEQ ID NO: 97); LC-CDR2, which includes KASTLQS (SEQ ID NO: 104); and LC-CDR3, which includes QQYKSAPYN (SEQ ID NO: 124).

[0132] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains NFYIQ (SEQ ID NO:46); HC-CDR2, which contains RINPRTGGTNYAQKFQG (SEQ ID NO:53); and HC-CDR3, which contains GAAAVNY (SEQ ID NO:80); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes KSSQSLFYSSNNKTYLA (SEQ ID NO:98); LC-CDR2, which includes WASTRES (SEQ ID NO:103); and LC-CDR3, which includes QQYYSTPLT (SEQ ID NO:114).

[0133] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity determination region (HC-CDR)1, which contains SYSMQ (SEQ ID NO:47); HC-CDR2, which contains AINSGGGTTYYADSVKG (SEQ ID NO:64); and HC-CDR3, which contains GGGNHDAIDF (SEQ ID NO:84); and light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which includes KSGQSLLYRSNNKNYLA (SEQ ID NO:99); LC-CDR2, which includes WASTRES (SEQ ID NO:103); and LC-CDR3, which includes QHYYSIPWT (SEQ ID NO:125).

[0134] On the other hand, this application provides an anti-Nogo-A antibody, which comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYYLQ (SEQ ID NO:43); HC-CDR2, which contains RINPKTGATNYTQKFQG (SEQ ID NO:61); and HC-CDR3, which contains VVY (SEQ ID NO:81); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGITNDLL (SEQ ID NO:95); LC-CDR2, which includes EASSLQG (SEQ ID NO:109); and LC-CDR3, which includes QHYYTTPFT (SEQ ID NO:126).

[0135] It also provides nucleic acids encoding anti-Nogo-A antibodies, compositions containing anti-Nogo-A antibodies, and methods for preparing and using anti-Nogo-A antibodies.

[0136] definition

[0137] As described herein, “treatment” or “treating” is a method of obtaining a beneficial or desired outcome, including clinical outcomes. For the purposes of this application, the beneficial or desired clinical outcome includes, but is not limited to, one or more of the following: relief of one or more symptoms caused by a disease, reduction of disease severity, stabilization of the disease (e.g., prevention or delay of disease exacerbation), prevention or delay of disease spread (e.g., metastasis), prevention or delay of disease recurrence, delay or slowing of disease progression, improvement of disease status, relief of the disease (partial or complete), reduction of the dosage of one or more other medications required to treat the disease, delay of disease progression, improvement or enhancement of quality of life, weight gain, and / or prolonged survival. Simultaneously, “treatment” also includes a reduction in disease pathological outcomes (e.g., inhibition of neurite growth in the case of nerve damage). The methods of this application consider any one or more aspects of these treatments.

[0138] The term "antibody" includes both full-length antibodies and their antigen-binding fragments. Full-length antibodies consist of two heavy chains and two light chains. Variable regions in both the light and heavy chains are responsible for antigen binding. The variable regions in both chains typically include three hypervariable loops, known as complementarity-determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3; heavy chain (HC) CDRs include HC-CDR1, HC-CDR2, and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified according to the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). Three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold supporting the hypervariable loop. The constant regions of the heavy and light chains do not participate in antigen binding but exhibit a variety of effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five main classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, characterized by having α, δ, ε, γ, and μ-type heavy chains, respectively. Several major antibody classes are subclassed, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain), or IgA2 (α2 heavy chain).

[0139] As described herein, the term "antigen-binding fragment" includes antibody fragments, such as diabody, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabody (ds-diabody), single-chain Fv (scFv), scFv dimers (bivalent diabody), multispecific antibodies, single-domain antibodies, nanobodies, domain antibodies, divalent domain antibodies, or any other antibody fragment capable of binding to an antigen but not containing a complete antibody structure. The antigen-binding fragment is capable of binding the same antigen to a parent antibody or a parent antibody fragment (such as a parental scFv). The antigen-binding fragment also includes fusion proteins comprising the antibody fragments described above. In some embodiments, the antigen-binding fragment may include one or more CDRs from a specific human antibody that have been grafted into a frame region from one or more different human antibodies.

[0140] As described herein, the term "epitope" refers to a specific set of atoms or amino acids on an antigen that an antibody or antibody portion binds to. If two antibodies or antibody portions exhibit competitive binding to an antigen, they may bind to the same epitope on the antigen.

[0141] As used herein, when the first antibody inhibits the binding of the second antibody to the Nogo-A target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at an equimolar concentration, the first antibody “competitively” binds to the Nogo-A target with the second antibody, and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody “epitope classification” method based on cross-competition.

[0142] As described herein, the terms "specifically bind," "specifically recognize," or "specific to" refer to measurable and reproducible interactions, such as antibody binding to a target that confirms the presence of that target in a heterogeneous group of molecules, including biomolecules. For example, an antibody's ability to specifically recognize a target (which may be an epitope) means that the antibody binds to that target with higher affinity, stronger binding, and / or more persistent binding compared to binding to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity at least 10 times greater than its binding affinity to other targets.

[0143] As described herein, an “isolated” anti-Nogo-A antibody is an anti-Nogo-A antibody that (1) is not related to naturally occurring proteins, (2) does not contain other proteins of the same origin, (3) is expressed by cells of a different species, or (4) does not exist in nature.

[0144] As described herein, the term “isolated nucleic acid” refers to a nucleic acid or combination thereof of genomic, cDNA, or synthetic origin. Depending on its origin, “isolated nucleic acid” means that it is (1) unrelated to all or part of the polynucleotides in “isolated nucleic acids” found in nature, (2) operablely ligable to polynucleotides not naturally associated with it, or (3) not present in nature as part of a longer sequence.

[0145] As used herein, the term “CDR” or “complementarity-determining region” refers to a discontinuous antigen-binding site found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat et al., USDept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al., J. Mol. Biol. 196: 901-917 (1987); Al-Lazikani B. et al. al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol. Biol. 262: 732-745 (1996); Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Lefranc MPet These specific regions have been described in al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlaps or subsets of amino acid residues when compared with each other. However, any definition used to indicate a CDR of an antibody or transplanted antibody or its variants is included within the scope of the terminology defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the aforementioned references for comparison. Algorithms and interfaces for CDR prediction are known in the art, including, for example, those described in Abhinandan and Martin, Mol. Immunol., 45:3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38:D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015). The entire contents of the references cited in this paragraph are incorporated herein by reference for the purposes of this application and one or more claims that may be included herein.

[0146] Table 1: CDR Definition

[0147]

[0148]

[0149] 1 The amino acid residue numbering follows the nomenclature method described in Kabat et al. above.

[0150] 2 The amino acid residue numbering follows the nomenclature method described in Chothia et al. above.

[0151] 3 The amino acid residue numbering follows the nomenclature method described in MacCallum et al. above.

[0152] 4 The amino acid residue numbering follows the nomenclature method described in Lefranc et al. above.

[0153] 5 The amino acid residue numbering follows the nomenclature method described in Honegger and Plückthun.

[0154] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody species or subclass, while the remainder of the chain is identical or homologous to the corresponding sequence in an antibody from another genus or belonging to another antibody species or subclass, as well as fragments of such antibodies, provided they possess the biological activity described in this application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).

[0155] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly and non-covalently linked. The folding of these two domains derives six hypervariable rings (three in the light chain and three in the heavy chain), which provide the antibody with amino acid residues for binding to the antigen and confer the antibody's specificity for antigen binding. However, even a single variable domain (or half of the Fv fragment, containing only three antigen-specific CDRs) can recognize and bind to antigens, although its affinity is lower than that of the complete binding site.

[0156] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a type of Fv containing V molecules linked together to form a single polypeptide chain. H and V L Antibody fragments of antibody domains. In some embodiments, the scFv polypeptide further includes V H and V LThe linker polypeptide between the domains allows scFv to form an ideal structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0157] The term "diabody" is used in V H and V L Small antibody fragments are prepared by constructing scFv fragments (see above) using short linkers (e.g., 5–10 residues) between domains. This allows the variable domains to pair between chains rather than within chains, resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. Bispecific double-chain antibodies are heterodimers of two “crossed” scFv fragments, where the V0 of the two antibodies... H and V L The domains are located on different polypeptide chains. Double-chain antibodies are fully described in EP404,097; WO 93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0158] The “humanized” form of non-human (e.g., rodent) antibodies is a chimeric antibody, which includes a minimal sequence derived from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (receptor antibodies), where the hypervariable region (HVR) residues of the receptor antibody are replaced by hypervariable region residues from non-human species such as mice, rats, rabbits, or non-human mammals that possess desirable antibody specificity, affinity, and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. Additionally, humanized antibodies may include residues not present in either the receptor or donor antibody. These modifications can further improve antibody performance. Typically, humanized antibodies contain substantially all, at least one, and usually two variable domains, where all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. Humanized antibodies may also optionally include at least a portion of the immunoglobulin constant region (Fc), typically the constant region of a human immunoglobulin. For details, please refer to Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

[0159] The "percentage of amino acid sequence identity (%)" or "homology" of the peptide and antibody sequences identified in this paper is defined as the percentage of identical amino acid residues in a candidate sequence compared to a peptide sequence, assuming that conserved substitutions are part of sequence identity. The percentage of amino acid sequence identity can be determined using various alignment methods within the scope of the art, such as publicly available computer software like BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine suitable parameters for measuring alignment, including any algorithm required to maximize alignment across the full length of the compared sequences. However, for the purposes of this paper, the percentage of amino acid sequence identity values ​​were generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).

[0160] The term "Fc receptor" or "FcR" is used to describe receptors that bind to the Fc region of antibodies. In some embodiments, the FcR described in this application is an FcR that binds to IgG antibodies (a type of γ receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternative splicing forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in their cytoplasmic domains. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine inhibitory motif (ITIM) (see M.in.). Annu.Rev.Immunol.15:203-234 (1997)). The term also includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and / or FcγRIIA-H131. FcRs are described in Ravetch and Kinet, Annu.Rev.Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J.Lab.Clin.Med.126:330-41 (1995). In this application, the term FcR covers other types of FcRs, including those to be identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for transferring maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0161] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC), consisting of an α-chain non-covalently bound to β2-microglobulin. The various functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from the mother to the newborn and in regulating serum IgG levels. As a rescue receptor, FcRn can bind and transport endocytotic IgG in its intact form both intracellularly and intercellularly, protecting it from the default degradation pathway.

[0162] The "CH1 domain" of the constant region of the human IgG heavy chain typically extends from amino acid 118 to amino acid 215 (EU numbering system).

[0163] The "hinge region" is typically defined as extending from Glu at position 216 to Pro at position 230 of human IgG1 (Burton, Molec. Immunol. 22:161-206 (1985)). By placing the first and last cysteine ​​residues that form the inter-heavy chain disulfide bond at the same positions as IgG1, it is possible to align the hinge regions of other IgG isotypes with the IgG1 sequence.

[0164] The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The unique feature of the CH2 domain is that it does not pair tightly with another region; instead, two N-terminal branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is speculated that the sugars may act as a substitute for domain-to-domain pairing, helping to maintain the stability of the CH2 domain. (Burton, Molec. Immunol. 22:161-206 (1985)).

[0165] The “CH3” domain includes the extension from the C-terminal residue to the CH2 domain within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, typically amino acid 446 or 447 of IgG).

[0166] "Functional Fc fragments" possess the "effective functions" inherent in the natural Fc region sequence. Exemplary "effective functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (such as B cell receptors; BCR). These effector functions typically require the Fc region to bind to a binding domain (such as the antibody variable region) and can be evaluated using a variety of experimental methods known in the art.

[0167] Antibodies with IgG Fc variants exhibiting "altered" FcR binding affinity or ADCC activity show enhanced or weakened FcR binding and / or ADCC activity compared to the parent peptide or peptides containing the native Fc sequence. Fc variants exhibiting "enhanced binding" to FcRs have higher binding affinity (e.g., lower apparent Kd or IC50) to at least one FcR compared to the parent peptide or peptides containing the native IgG Fc sequence. 50(Value). In some embodiments, the binding affinity is enhanced by 3 times compared to the parent peptide, for example, 5, 10, 25, 50, 60, 100, 150, 200, or even up to 500 times, or the binding affinity is increased by 25% to 1000%. Fc variants exhibit “reduced binding” to FcRs, having a lower affinity for at least one FcR compared to the parent peptide (e.g., higher apparent Kd or IC). 50 (Value). Compared with the parent peptide, its binding ability is reduced by 40% or more.

[0168] Antibody-dependent cell-mediated cytotoxicity (ADCC) is a form of cytotoxicity in which secreted Ig binds to Fc receptors (FcRs) present on certain cytotoxic cells, such as natural killer (NK) cells, neutrophils, and macrophages. This allows these cytotoxic effector cells to specifically bind to target cells carrying antigens and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are essential for this killing. Among the main cell types mediating ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). The ADCC activity of target molecules can be assessed by in vitro ADCC experiments, described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMCs) and natural killer cells (NK cells). Alternatively, or additionally, the ADCC activity of the target molecule can also be assessed in vivo, as described, for example, in animal models disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).

[0169] Peptides containing Fc region variants exhibit "enhanced ADCC activity" or are more effective at mediating ADCC effects in the presence of human effector cells compared to peptides containing wild-type IgG Fc or parental peptides. These peptides, when experimentally present in substantially the same quantity as those containing wild-type IgG Fc (or parental peptides), mediate ADCC more effectively both in vitro and in vivo. Such variants are typically identified using any in vitro ADCC assay known in the art, such as experiments or methods for identifying ADCC activity, for example in animal models. In some embodiments, such variants mediate ADCC with a 5 to 100-fold, for example, 25 to 50-fold, efficiency improvement compared to wild-type Fc (or parental peptide).

[0170] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (a subclass with a suitable structure) that binds to a homologous antigen. To assess complement activation, CDC assays can be performed, as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Peptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capacity are described in U.S. Patent Nos. 6,194,551B1 and WO99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al., J. Immunol. 164:4178-4184 (2000).

[0171] Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate forms of each other and encode the same amino acid sequence. Nucleotide sequences encoding proteins or RNA may also include introns; for example, nucleotide sequences encoding proteins may contain introns in certain forms.

[0172] The term "operationally ligated" refers to a functional link between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling the latter to be expressed. For example, the first and second nucleotide sequences are operably ligated when they are in a functional relationship. Similarly, if a promoter affects the transcription or expression of a coding sequence, the promoter and coding sequence are operably ligated. Typically, operably ligated DNA sequences are contiguous, and, if necessary, two protein-coding regions can be ligated within the same reading frame.

[0173] "Homology" refers to the sequence similarity or identity between two polypeptides or two nucleic acid molecules. If the same position in two compared sequences is the same base or amino acid monomer subunit, for example, if both DNA molecules have adenine at the same position, then the two DNA molecules are homologous at that position. The percentage of homology between two sequences is a function calculated by multiplying the number of matching or homologous positions in the two sequences to the total number of positions, and then multiplying by 100. For example, if 6 out of 10 positions in two sequences are matching or homologous, then the two sequences are 60% homologous. For instance, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally, when comparing two sequences, the goal is to obtain the maximum homology.

[0174] The “effective amount” of the anti-Nogo-A antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose. The “effective amount” can be determined empirically and by known methods associated with said purpose.

[0175] The term "therapeutic effective dose" refers to the dosage of the anti-Nogo-A antibody or its composition disclosed herein that is effective in treating an individual's disease or symptoms. For example, in the case of spinal cord injury, a therapeutic effective dose of the anti-Nogo-A antibody or its composition refers to the dosage that promotes (i.e., to some extent restores) the sprouting and regeneration of the damaged corticospinal tract (CST); promotes (i.e., to some extent restores) the growth of the growth cone; promotes (i.e., to some extent restores) the regeneration of damaged neurites; reduces (i.e., to some extent relieves) the inhibition of neurite growth; reduces (i.e., to some extent relieves) the inhibition of growth cone growth; and / or alleviates to some extent one or more symptoms of the underlying disease associated with spinal cord injury. In some embodiments, a therapeutic effective dose refers to the dosage that prolongs the patient's survival. In some embodiments, a therapeutic effective dose refers to the dosage that improves the patient's progression-free survival.

[0176] As used herein, "pharmaceuticalally acceptable" or "pharmacologically compatible" means a material that has no biological activity or other undesirable properties, such as the ability to be incorporated into a pharmaceutical composition given to a patient without causing significant adverse biological reactions, or that does not interact harmfully with any other components contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicological or manufacturing testing and / or are included in the inactive ingredient guidelines prepared by the U.S. Food and Drug Administration.

[0177] The embodiments of this application described herein should be understood to include embodiments that are “composed of” and / or “substantially composed of”.

[0178] In this article, “about” is used to refer to a numerical value or parameter, including (and descriptions) variations for that value or parameter itself. For example, a description involving “about X” includes a description of “X”.

[0179] As used in this article, mentioning "not" a value or parameter usually means and describes something other than a certain value or parameter. For example, "This method cannot be used to treat type X cancer" means that this method is generally used to treat other types of cancer besides type X cancer.

[0180] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein and in the claims include plural objects.

[0181] Anti-Nogo-A antibody

[0182] On one hand, this application provides anti-Nogo-A antibodies against humans and / or rhesus monkeys that specifically bind to Nogo-A. The anti-Nogo-A antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the other hand, this application provides isolated antibodies that bind to Nogo-A. Anticipated anti-Nogo-A antibodies include, for example, full-length anti-Nogo-A antibodies (such as full-length IgG1 or IgG4), anti-Nogo-A single-chain antibodies, anti-Nogo-AFc fusion proteins, multispecific (such as bispecific) anti-Nogo-A antibodies, anti-Nogo-A immunoconjugates, and the like. In some embodiments, the anti-Nogo-A antibody is a full-length antibody (such as full-length IgG1 or IgG4) or its antigen-binding fragment that specifically binds to Nogo-A. In some embodiments, the anti-Nogo-A antibody is Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, or linear antibody. In some embodiments, an antibody that specifically binds to Nogo-A means that the antibody's affinity for Nogo-A is at least 10 times greater than its affinity for binding to non-target antibodies (including, for example, 10, 10). 2 10 3 10 4 10 5 10 6 , or 10 7 (Multiple times). In some embodiments, non-target refers to an antigen that is not Nogo-A. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence-activated cell sorting (FACS) analysis, or radioimmunoprecipitation (RIA). Kd value can be determined by methods known in the art, such as surface plasmon resonance (SPR) technology or biolayer interference (BLI) technology.

[0183] While this document discusses anti-Nogo-A antibodies containing human sequences (e.g., human heavy and light chain variable domains containing human CDR sequences), non-human anti-Nogo-A antibodies are also considered. In some embodiments, non-human anti-Nogo-A antibodies comprise the human CDR sequence and non-human frame region sequence of the anti-Nogo-A antibodies described herein. In some embodiments, the non-human frame region sequence comprises any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., cows, bulls, buffalo), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., apes, macaques), etc. In some embodiments, non-human anti-Nogo-A antibodies comprise anti-Nogo-A antibodies generated by transplanting one or more human CDR sequences as described herein into a non-human frame region (e.g., a mouse or chicken frame region sequence).

[0184] The exemplary human Nogo-A exon 3 encoding NiG amino acid sequence comprises or consists of the amino acid sequence shown in SEQ ID NO: 25. The exemplary rhesus monkey NiG amino acid sequence comprises or consists of the amino acid sequence shown in SEQ ID NO: 26. The exemplary rat NiG amino acid sequence comprises or consists of the amino acid sequence shown in SEQ ID NO: 27.

[0185] In some embodiments, the anti-Nogo-A antibody described herein specifically recognizes an epitope in human Nogo-A. In some embodiments, the anti-Nogo-A antibody cross-reacts with Nogo-A in species other than humans. In some embodiments, the anti-Nogo-A antibody is completely specific to human Nogo-A and does not cross-react with other non-human species.

[0186] In some embodiments, the anti-Nogo-A antibody cross-reacts with at least one allelic variant of the Nogo-A protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) compared to the naturally occurring Nogo-A protein (or a fragment thereof) (e.g., conserved substitutions). In some embodiments, the anti-Nogo-A antibody does not cross-react with any allelic variant of the Nogo-A protein (or a fragment thereof).

[0187] In some embodiments, the anti-Nogo-A antibody cross-reacts with at least one interspecies variant of the Nogo-A protein. In some embodiments, for example, the Nogo-A protein (or a fragment thereof) is human Nogo-A, and the interspecies variant of the Nogo-A protein (or a fragment thereof) is a variant found in cynomolgus monkeys. In some embodiments, the anti-Nogo-A antibody does not cross-react with any interspecies variant of the Nogo-A protein.

[0188] In some embodiments, any of the anti-Nogo-A antibodies described herein comprises an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG1 type heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG2 type heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG3 type heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG4 type heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:21. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:22. In some embodiments, the anti-Nogo-A antibody comprises a κ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:23. In some embodiments, the anti-Nogo-A antibody comprises a λ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:24. In some embodiments, the anti-Nogo-A antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.

[0189] In some embodiments, the anti-Nogo-A antibody includes a heavy chain variable domain (V... H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains DYGMH (SEQ ID NO:1); HC-CDR2, which contains SISHTGKTVFYGESVKG (SEQ ID NO:3); and HC-CDR3, which contains TELGGDNWFDV (SEQ ID NO:5); and light chain variable structural domain (V L ), the V LIt includes: light chain complementarity determination region (LC-CDR)1, which contains TGSSSNIGGYDVY (SEQ ID NO:7); LC-CDR2, which contains DNNKRPS (SEQ ID NO:9); and LC-CDR3, which contains AAWDDSLYGYI (SEQ ID NO:11).

[0190] In some embodiments, the anti-Nogo-A antibody contains V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and HC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0191] In some embodiments, the anti-Nogo-A antibody contains V H The V H It comprises: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:3; and HC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:5.

[0192] In some embodiments, the anti-Nogo-A antibody contains V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:7 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:11 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0193] In some embodiments, the anti-Nogo-A antibody contains V L The V LIt includes: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:7; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:9; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:11.

[0194] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in SEQ ID NO:3 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising the amino acid sequence shown in SEQ ID NO:5 or a variant thereof, said variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:7 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:11 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0195] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:3; and HC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:5; and V L The V L It comprises: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:7; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:9; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:11.

[0196] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:3; HC-CDR3, which contains the amino acid sequence SEQ ID NO:5; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:7; LC-CDR2, which contains the amino acid sequence SEQ ID NO:9; LC-CDR3, which contains the amino acid sequence SEQ ID NO:11; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0197] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:3; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:5; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:7; LC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:11.

[0198] In some embodiments, the anti-Nogo-A antibody contains V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:13-16 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:18-19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0199] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:13. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V LIt contains V as shown in the amino acid sequence SEQ ID NO:18. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0200] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:14. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0201] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:15. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0202] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:16. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:19 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0203] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-16 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-16; and V L The V LThe antibody comprises any of the amino acid sequences shown in SEQ ID NOs:18-19 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:18-19. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-16, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:18-19.

[0204] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:13 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:13; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:18 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:18. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:13, and V L The V L It contains the amino acid sequence SEQ ID NO:18.

[0205] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:14 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:14; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:14, and V L The V L It contains the amino acid sequence SEQ ID NO:19.

[0206] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:15 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:15; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:15, and V L The V L It contains the amino acid sequence SEQ ID NO:19.

[0207] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:16 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:16; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the anti-Nogo-A antibody comprises V H The VH Contains the amino acid sequence SEQ ID NO:16, and V L The V L It contains the amino acid sequence SEQ ID NO:19.

[0208] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:4; HC-CDR3, which contains the amino acid sequence SEQ ID NO:6; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:8; LC-CDR2, which contains the amino acid sequence SEQ ID NO:10; LC-CDR3, which contains the amino acid sequence SEQ ID NO:12; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0209] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:4; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:6; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:8; LC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:12.

[0210] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:17. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:20. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0211] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:17 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:17; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:20 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:20. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:17, and V L The V L It contains the amino acid sequence SEQ ID NO:20.

[0212] In some embodiments, the anti-Nogo-A antibody includes a heavy chain variable domain (V... H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SYGMH (SEQ ID NO:28); HC-CDR2, which contains VIWYHGSKKYYADSVKD (SEQ ID NO:48); and HC-CDR3, which contains SIAETTDYGLDS (SEQ ID NO:65); and light chain variable domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RSSQSLLYRGGKTFLY (SEQ ID NO:85); LC-CDR2, which includes ELSNRAS (SEQ ID NO:100); and LC-CDR3, which includes MQGIQLPWT (SEQ ID NO:111).

[0213] In some embodiments, the anti-Nogo-A antibody contains V H The V HIt comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:28 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:48 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and HC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:65 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0214] In some embodiments, the anti-Nogo-A antibody contains V H The V H It includes: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:28; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:48; and HC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:65.

[0215] In some embodiments, the anti-Nogo-A antibody contains V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:85 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:100 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:111 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0216] In some embodiments, the anti-Nogo-A antibody contains V L The V L It includes: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:85; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:100; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:111.

[0217] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:28 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in SEQ ID NO:48 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising the amino acid sequence shown in SEQ ID NO:65 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:85 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:100 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:111 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0218] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:28; HC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:48; and HC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:65; and V L The V L It comprises: LC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:85; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:100; and LC-CDR3, which contains the amino acid sequence shown in SEQ ID NO:111.

[0219] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:28; HC-CDR2, which contains the amino acid sequence SEQ ID NO:48; HC-CDR3, which contains the amino acid sequence SEQ ID NO:65; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:85; LC-CDR2, which contains the amino acid sequence SEQ ID NO:100; LC-CDR3, which contains the amino acid sequence SEQ ID NO:111; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0220] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:28; HC-CDR2, which contains the amino acid sequence SEQ ID NO:48; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:65; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:85, LC-CDR2, which contains the amino acid sequence SEQ ID NO:100, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:111.

[0221] In some embodiments, the anti-Nogo-A antibody contains V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:127-128 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:150-151 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0222] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:127. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:150. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0223] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:128. HIncludes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:151. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0224] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:128. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:150. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0225] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:127-128 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:127-128; and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:150-151 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:150-151. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:127-128, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:150-151.

[0226] In some embodiments, the anti-Nogo-A antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:127; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:150 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:150. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:127, and V L The V L It contains the amino acid sequence SEQ ID NO:150.

[0227] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:128 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:128; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:151 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:151. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:128, and V L The V L It contains the amino acid sequence SEQ ID NO:151.

[0228] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:128 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:128; and V L The VL The antibody comprises the amino acid sequence SEQ ID NO:150 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:150. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:128, and V L The V L It contains the amino acid sequence SEQ ID NO:150.

[0229] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:29; HC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:66, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:86; LC-CDR2, which contains the amino acid sequence SEQ ID NO:101; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:112, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids.

[0230] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:29; HC-CDR2, which contains the amino acid sequence SEQ ID NO:49; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:66; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:86; LC-CDR2, which contains the amino acid sequence SEQ ID NO:101; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:112.

[0231] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:129. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:152. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0232] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:129 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:129; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:152 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:152. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:129, and V L The V L It contains the amino acid sequence SEQ ID NO:152.

[0233] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:30; HC-CDR2, which contains the amino acid sequence SEQ ID NO:50; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:67, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:87; LC-CDR2, which contains the amino acid sequence SEQ ID NO:102; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:113, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0234] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:30; HC-CDR2, which contains the amino acid sequence SEQ ID NO:50; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:67; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:87, LC-CDR2, which contains the amino acid sequence SEQ ID NO:102, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:113.

[0235] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:130. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:153. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0236] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:130 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:130; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:153 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:153. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:130, and V L The V L It contains the amino acid sequence SEQ ID NO:153.

[0237] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:68, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0238] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:68; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114.

[0239] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:131. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:154. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0240] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:131 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:131; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:154 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:154. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:131, and V L The V L It contains the amino acid sequence SEQ ID NO:154.

[0241] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:32; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:69, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0242] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:32; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:69; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114.

[0243] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:132. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:155. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0244] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:132 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:132; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:155 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:155. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:132, and V L The V L It contains the amino acid sequence SEQ ID NO:155.

[0245] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:33; HC-CDR2, which contains the amino acid sequence SEQ ID NO:52; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:70, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:89; LC-CDR2, which contains the amino acid sequence SEQ ID NO:104; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:115, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0246] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:33; HC-CDR2, which contains the amino acid sequence SEQ ID NO:52; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:70; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:89, LC-CDR2, which contains the amino acid sequence SEQ ID NO:104, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:115.

[0247] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:133. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:156. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0248] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:133 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:133; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:156 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:156. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:133, and V L The V L It contains the amino acid sequence SEQ ID NO:156.

[0249] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:34; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:71, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0250] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:34; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:71; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114.

[0251] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:134. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:157. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0252] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:134 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:134; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:157 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:157. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:134, and V L The V L It contains the amino acid sequence SEQ ID NO:157.

[0253] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:35; HC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:72, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:90; LC-CDR2, which contains the amino acid sequence SEQ ID NO:105; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:116, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0254] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:35; HC-CDR2, which contains the amino acid sequence SEQ ID NO:54; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:72; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:90, LC-CDR2, which contains the amino acid sequence SEQ ID NO:105, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:116.

[0255] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:135. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:158. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0256] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:135 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:135; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:158 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:158. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:135, and V L The V L It contains the amino acid sequence SEQ ID NO:158.

[0257] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:36; HC-CDR2, which contains the amino acid sequence SEQ ID NO:55; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:73, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91; LC-CDR2, which contains the amino acid sequence SEQ ID NO:106; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0258] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:36; HC-CDR2, which contains the amino acid sequence SEQ ID NO:55; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:73; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91, LC-CDR2, which contains the amino acid sequence SEQ ID NO:106, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117.

[0259] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:136. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:159. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0260] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:136 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:136; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:159 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:159. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:136, and V L The V L It contains the amino acid sequence SEQ ID NO:159.

[0261] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:37; HC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:74, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91; LC-CDR2, which contains the amino acid sequence SEQ ID NO:106; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0262] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:37; HC-CDR2, which contains the amino acid sequence SEQ ID NO:56; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:74; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:91, LC-CDR2, which contains the amino acid sequence SEQ ID NO:106, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:117.

[0263] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:137. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:159. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0264] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:137 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:137; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:159 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:159. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:137, and V L The V L It contains the amino acid sequence SEQ ID NO:159.

[0265] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:57; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:75, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:92; LC-CDR2, which contains the amino acid sequence SEQ ID NO:107; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:118, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0266] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:31; HC-CDR2, which contains the amino acid sequence SEQ ID NO:57; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:75; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:92, LC-CDR2, which contains the amino acid sequence SEQ ID NO:107, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:118.

[0267] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:138. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:160. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0268] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:138 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:138; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:160 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:160. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:138, and V L The V L It contains the amino acid sequence SEQ ID NO:160.

[0269] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:38; HC-CDR2, which contains the amino acid sequence SEQ ID NO:58; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:76, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:93; LC-CDR2, which contains the amino acid sequence SEQ ID NO:108; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:119, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0270] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:38; HC-CDR2, which contains the amino acid sequence SEQ ID NO:58; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:76; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:93, LC-CDR2, which contains the amino acid sequence SEQ ID NO:108, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:119.

[0271] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:139. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:161. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0272] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:139 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:139; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:161 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:161. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:139, and V L The V L It contains the amino acid sequence SEQ ID NO:161.

[0273] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:39; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:77, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0274] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:39; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:77; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120.

[0275] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:140. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:162. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0276] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:140 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:140; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:162 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:162. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:140, and V L The V L It contains the amino acid sequence SEQ ID NO:162.

[0277] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:40; HC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:78, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:94; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:121, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0278] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:40; HC-CDR2, which contains the amino acid sequence SEQ ID NO:59; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:78; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:94, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:121.

[0279] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:141. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:163. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0280] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:141 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:141; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:163 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:163. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:141, and V L The V L It contains the amino acid sequence SEQ ID NO:163.

[0281] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:41; HC-CDR2, which contains the amino acid sequence SEQ ID NO:60; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:79, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0282] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:41; HC-CDR2, which contains the amino acid sequence SEQ ID NO:60; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:79; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114.

[0283] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:142. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:164. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0284] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:142 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:142; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:164 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:164. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:142, and V L The V L It contains the amino acid sequence SEQ ID NO:164.

[0285] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:42; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0286] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:42; HC-CDR2, which contains the amino acid sequence SEQ ID NO:51; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:88, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:120.

[0287] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:143. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:165. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0288] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:143 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:143; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:165 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:165. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:143, and V L The V L It contains the amino acid sequence SEQ ID NO:165.

[0289] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95; LC-CDR2, which contains the amino acid sequence SEQ ID NO:109; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:122, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0290] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95, LC-CDR2, which contains the amino acid sequence SEQ ID NO:109, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:122.

[0291] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:166. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0292] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:144; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:166 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:166. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:144, and V L The V L It contains the amino acid sequence SEQ ID NO:166.

[0293] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:44; HC-CDR2, which contains the amino acid sequence SEQ ID NO:62; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:82, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:96; LC-CDR2, which contains the amino acid sequence SEQ ID NO:110; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:123, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0294] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:44; HC-CDR2, which contains the amino acid sequence SEQ ID NO:62; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:82; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:96, LC-CDR2, which contains the amino acid sequence SEQ ID NO:110, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:123.

[0295] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:167. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0296] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:145; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:167 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:167. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:145, and V L The V L It contains the amino acid sequence SEQ ID NO:167.

[0297] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:45; HC-CDR2, which contains the amino acid sequence SEQ ID NO:63; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:83, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:97; LC-CDR2, which contains the amino acid sequence SEQ ID NO:104; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:124, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0298] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:45; HC-CDR2, which contains the amino acid sequence SEQ ID NO:63; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:83; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:97, LC-CDR2, which contains the amino acid sequence SEQ ID NO:104, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:124.

[0299] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:146. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:168. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0300] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:146 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:146; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:168 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:168. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:146, and V L The V L It contains the amino acid sequence SEQ ID NO:168.

[0301] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:46; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:98; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0302] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:46; HC-CDR2, which contains the amino acid sequence SEQ ID NO:53; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:80; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:98, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:114.

[0303] In some embodiments, the anti-Nogo-A antibody contains V HIt contains V as shown in the amino acid sequence SEQ ID NO:147. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:169. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0304] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:147 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:147; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:169 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:169. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:147, and V L The V L It contains the amino acid sequence SEQ ID NO:169.

[0305] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:47; HC-CDR2, which contains the amino acid sequence SEQ ID NO:64; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:84, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:99; LC-CDR2, which contains the amino acid sequence SEQ ID NO:103; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:125, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0306] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:47; HC-CDR2, which contains the amino acid sequence SEQ ID NO:64; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:84; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:99, LC-CDR2, which contains the amino acid sequence SEQ ID NO:103, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:125.

[0307] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:148. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:170. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0308] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:148 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:148; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:170 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:170. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:148, and V L The V L It contains the amino acid sequence SEQ ID NO:170.

[0309] In some embodiments, the anti-Nogo-A antibody contains V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95; LC-CDR2, which contains the amino acid sequence SEQ ID NO:109; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:126, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0310] In some embodiments, the anti-Nogo-A antibody contains V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:43; HC-CDR2, which contains the amino acid sequence SEQ ID NO:61; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:81; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:95, LC-CDR2, which contains the amino acid sequence SEQ ID NO:109, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:126.

[0311] In some embodiments, the anti-Nogo-A antibody contains V H It contains V as shown in the amino acid sequence SEQ ID NO:149. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:171. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0312] In some embodiments, the anti-Nogo-A antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:149 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:149; and VL The V L The antibody comprises the amino acid sequence SEQ ID NO:171 or a variant thereof, said variant having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:171. In some embodiments, the anti-Nogo-A antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:149, and V L The V L It contains the amino acid sequence SEQ ID NO:171.

[0313] In some embodiments, the amino acid substitutions described above are limited to the “Exemplary Substitutions” shown in Table 4 herein. In some embodiments, the amino acid substitutions are limited to the “Preferred Substitutions” shown in Table 4 herein.

[0314] In some embodiments, the functional epitope can be resolved using a combined alanine scanning method. In this process, the combined alanine scanning technique can be used to identify the amino acids in the Nogo-A protein essential for interaction with anti-Nogo-A antibodies. In some embodiments, the epitope is conformational, and the epitope can also be identified using the crystal structure of an anti-Nogo-A antibody that binds to the Nogo-A protein.

[0315] In some embodiments, this application provides an antibody that competitively binds to Nogo-A, in conjunction with any of the anti-Nogo-A antibodies described herein. In some embodiments, an antibody is provided that is capable of competitively binding to an epitope on Nogo-A, in conjunction with any of the anti-Nogo-A antibodies described herein. In some embodiments, an anti-Nogo-A antibody is provided that contains V H and V L The anti-Nogo-A antibody molecule binds to the same epitope, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149, and the V L Contains the amino acid sequence shown in any of SEQ ID NOs:18-20, 150-171. In some embodiments, an anti-Nogo-A antibody is provided, which, together with V H and V L The anti-Nogo-A antibody competitively binds to Nogo-A, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149, and the V L It contains any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171.

[0316] In some embodiments, a competition assay can be used to identify monoclonal antibodies that competitively bind to Nogo-A with the anti-Nogo-A antibody described herein. A competition assay can determine whether two antibodies bind to the same epitope by identifying identical or spatially overlapping epitopes or by one antibody competitively inhibiting the binding of another antibody to the antigen. In some embodiments, such a competitive antibody binds to the same epitope as the antibody described herein. Some exemplary competition assays include, but are not limited to, conventional assays as described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving antibody-bound epitopes are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, if each antibody blocks 50% or more of the binding of another antibody, they are said to bind to the same epitope. In some embodiments, the antibody competing with the anti-Nogo-A antibody described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.

[0317] Exemplary anti-Nogo-A antibody sequences are shown in Tables 2 and 3, where CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that various known algorithms exist for predicting CDR locations and defining the variable regions of the antibody's light and heavy chains. CDRs containing antibodies as described herein, V H and / or V L Sequences, but antibodies based on prediction algorithms rather than those exemplified in the table below are also within the scope of this application.

[0318] Table 2. Exemplary anti-Nogo-A antibody CDR sequences

[0319]

[0320] Table 2A Exemplary CDR Sequences of Anti-Nogo-A Antibodies

[0321]

[0322]

[0323]

[0324]

[0325] Table 3 Exemplary Sequences

[0326]

[0327]

[0328]

[0329] Table 3A Example Sequences

[0330]

[0331]

[0332]

[0333] Nogo-A

[0334] Nogo-A protein is a member of the plasma membrane protein family. Nogo-A, Nogo-B, and Nogo-C are three protein products encoded by the plasma membrane protein 4 (RTN4, also known as NOGO) gene. These three isoforms share the same C-terminal reticulum homology domain (RTN). This RTN domain is highly similar to proteins encoded by the other three reticulum genes RTN1, RTN2, and RTN3 (GrandPre et al., Nature, 2000; Oertle et al., Trends Cell Biol. 2003), whose functions in the nervous system and other organs are largely unknown. The RTN domain of the Nogo protein contains two long hydrophobic segments, each long enough to span the cell membrane twice. They are linked together by a 66-amino acid segment called Nogo-66 (GrandPre et al., Nature, 2000). The N-terminal structures of Nogo-A, Nogo-B, and Nogo-C differ considerably, with only Nogo-A demonstrating a strong inhibitory effect in the central nervous system (GrandPre et al., Nature, 2000; Huber et al., J Neurosci, 2002). This indicates that an important functional domain is located in a specific region of the N-terminus of Nogo-A. By screening Nogo-A deletion construct libraries, a region with inhibitory activity against neurite growth and fibroblast proliferation was discovered, named Nogo-A-Δ20 (Oertle et al., J Neurosci, 2003; Kempf A et al., PLoSBiol. 2014). However, the Nogo-66 domain at the C-terminus of Nogo-A is also considered to have strong inhibitory activity against neurite growth (Fournier et al., Nature, 2001). While sufficient to exert their inhibitory function, Nogo-A-Δ20 and Nogo-66 have been shown to have stronger activity when they are part of a larger Nogo-A derivative fragment, such as Nogo-A-ext (also known as NiR-G, mouse aa 1-979) or Nogo-22 (mouse aa 966-1163) (Huebner et al., J Biol Chem, 2011; Oertle et al., J Neurosci, 2003).

[0335] Nogo-A receptor

[0336] Nogo-A exerts its inhibitory activity through two distinct extracellular domains, Nogo-A-Δ20 (mouse aa544-725) and Nogo-66 (mouse aa1026-1091) (Schwab ME et al., Nat Rev Neurosci. 2010; Oertle T et al., J Neurosci. 2003). The first Nogo receptor identified was the glycosylphosphatidylinositol (GPI)-linked leucine-rich repeat (LRR) protein Nogo receptor 1 (NgR1, also known as the Nogo-66 receptor and plasma membrane protein 4 receptor) (Fournier AE et al., Nature, 2001). NgR1 consists of 473 amino acids and includes an N-terminal signal sequence, eight leucine-rich repeats (LRRs) LRR1-LRR8, a leucine-rich repeat C-terminal domain (LRRCT) (these three regions together form the extracellular domain), and a GPI anchoring domain. NgR1 connects to the external neuronal plasma membrane via GPI anchoring structures. NgR1 is not expressed in early development in rodents or chicks, but shows high expression levels in adult animals; NgR1 is expressed in most CNS regions, including the spinal cord (Hunt et al., J Neurocytol. 2002a,b). Nogo-A binds to NgR1 through its inhibitory Nogo-66 domain, initiating an intracellular signaling cascade. Because NgR does not contain a transmembrane domain, signal transduction requires the transduction of the NgR / ligand interaction signal to the co-receptor p75 or TROY and LINGO1, forming a functional ternary complex that inhibits neurite growth. This binding leads to intracellular Ca2+ via an unknown intermediate. 2+ Increased levels of NgR1 and activation of the Rho-Rho-related coiled protein kinase (ROCK) pathway. Through RHOA signaling, the actin cytoskeleton becomes unstable, leading to growth cone collapse. In addition to NgR1, Nogo-66 also induces growth inhibition through interactions with accessory proteins and paired immunoglobulin-like receptor B (PIRB) (Atwal JK et al., Science. 2008). NgR1 also binds to growth-inhibiting myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (OMGP) (Domeniconi, M et al., Neuron, 2002; Wang, KC et al., Nature, 2002).

[0337] Anissa Kempf et al. discovered that the G protein-coupled receptor (GPCR) sphingosine 1-phosphate receptor 2 (S1PR2) is a functional receptor for the Δ20 domain of Nogo-A (Kempf A et al., PLoS Biol. 2014.). Interference with S1PR2 activity via pharmacological or genetic pathways can block Nogo-A-Δ20-mediated inhibition. This study also demonstrated that Nogo-A-Δ20 binds to S1PR2 via extracellular receptor loops 2 and 3, which differs from the previously described S1P binding site (Hanson MA et al., Science. 2012.). Nogo-A-Δ20 signals via G protein G13, leukemia-associated Rho guanine exchange factor (RhoGEF) LARG, and RhoA. Knockout or blockade of S1PR2 counteracts the Nogo-A-Δ20 and myelin-mediated inhibition of neuronal extracellular growth and cell proliferation. Acute S1PR2 blockade increases long-term synaptic plasticity in the hippocampus and cortex, similar to the neutralizing effect of Nogo-A. These results reinforce the recently proposed physiological role of Nogo-A in limiting synaptic plasticity to stabilize neuronal circuits (Mironova YA et al., Trends Neurosci. 2013.).

[0338] Full-length anti-Nogo-A antibody

[0339] In some embodiments, the anti-Nogo-A antibody is a full-length anti-Nogo-A antibody. In some embodiments, the full-length anti-Nogo-A antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-Nogo-A antibody includes a constant IgG region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the full-length anti-Nogo-A antibody includes a λ light chain constant region. In some embodiments, the full-length anti-Nogo-A antibody includes a κ light chain constant region. In some embodiments, the full-length anti-Nogo-A antibody is a full-length human anti-Nogo-A antibody. In some embodiments, the full-length anti-Nogo-A antibody includes a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-Nogo-A antibody includes an altered or otherwise modified Fc sequence such that it has enhanced effector functions of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

[0340] Therefore, for example, in some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, the anti-Nogo-A antibody specifically binding to Nogo-A. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0341] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG2 constant region is provided, the anti-Nogo-A antibody specifically binding to Nogo-A. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0342] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG3 constant region is provided, the anti-Nogo-A antibody specifically binding to Nogo-A. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0343] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, the anti-Nogo-A antibody specifically binding to Nogo-A. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0344] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 3-4, 48-64, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 5-6, 65-84, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a constant region of IgG1; and b) a light chain variable domain comprising: LC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a constant region of IgG1; and b) a light chain variable domain comprising: HC ... The amino acid sequences or variants thereof shown in SEQ ID NOs: 7-8, 85-99, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 9-10, 100-110, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 11-12, 111-126, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0345] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG2 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 3-4, 48-64, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 5-6, 65-84, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a constant region of IgG2 ... variable region comprising: a constant region of IgG2; and b) a variable region comprising: a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; and c) a constant region of IgG2; The amino acid sequences or variants thereof shown in SEQ ID NOs: 7-8, 85-99, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 9-10, 100-110, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 11-12, 111-126, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 24.

[0346] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG3 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 3-4, 48-64, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 5-6, 65-84, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising an amino acid sequence or a variant thereof shown in SEQ ID NOs: 1-2, 28-47 ... The amino acid sequences or variants thereof shown in SEQ ID NOs: 7-8, 85-99, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 9-10, 100-110, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences or variants thereof shown in SEQ ID NOs: 11-12, 111-126, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO: 24.

[0347] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 1-2, 28-47, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 3-4, 48-64, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising an amino acid sequence or a variant thereof shown in any of SEQ ID NOs: 5-6, 65-84, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising an amino acid sequence or a variant thereof shown in SEQ ID NOs: 1-2, 28-47 ... The amino acid sequences or variants thereof shown in SEQ ID NOs:7-8, 85-99, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains amino acid sequences or variants thereof shown in SEQ ID NOs:9-10, 100-110, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains amino acid sequences or variants thereof shown in SEQ ID NOs:11-12, 111-126, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0348] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-6, 65-84; or a variant of the heavy chain variable domain comprising a substitution of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-6, 65-84; or a variant of the heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 1 The amino acid sequences shown in NOs:9-10 and 100-110, and LC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:11-12 and 111-126, or a variant of the light chain variable domain, wherein the LC-CDR sequence comprises substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5). In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0349] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-6, 65-84; or a variant of the heavy chain variable domain comprising a substitution of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-6, 65-84; or a variant of the heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 7-8, 85-99; and HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-6, 65-84; or a variant of the heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in The amino acid sequences shown in NOs:9-10 and 100-110, and LC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:11-12 and 111-126, or a variant of the light chain variable domain, wherein the LC-CDR sequence comprises substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5). In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0350] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:5-6, 65-84; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:7-8, 85-99; LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:9-10, 100-110; and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:11-12, 111-126. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0351] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-2, 28-47; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:3-4, 48-64; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:5-6, 65-84; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:7-8, 85-99; LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:9-10, 100-110; and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:11-12, 111-126. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0352] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising amino acid sequence SEQ ID NO:5; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:7, LC-CDR2 comprising amino acid sequence SEQ ID NO:9, and LC-CDR3 comprising amino acid sequence SEQ ID NO:11. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0353] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing amino acid sequence SEQ ID NO:2, HC-CDR2 containing amino acid sequence SEQ ID NO:4, and HC-CDR3 containing amino acid sequence SEQ ID NO:6; and b) a light chain variable domain comprising: LC-CDR1 containing amino acid sequence SEQ ID NO:8, LC-CDR2 containing amino acid sequence SEQ ID NO:10, and LC-CDR3 containing amino acid sequence SEQ ID NO:12. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0354] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing the amino acid sequence SEQ ID NO:28, HC-CDR2 containing the amino acid sequence SEQ ID NO:48, and HC-CDR3 containing the amino acid sequence SEQ ID NO:65; and b) a light chain variable domain comprising: LC-CDR1 containing the amino acid sequence SEQ ID NO:85, LC-CDR2 containing the amino acid sequence SEQ ID NO:100, and LC-CDR3 containing the amino acid sequence SEQ ID NO:111. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0355] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing the amino acid sequence SEQ ID NO:29, HC-CDR2 containing the amino acid sequence SEQ ID NO:49, and HC-CDR3 containing the amino acid sequence SEQ ID NO:66; and b) a light chain variable domain comprising: LC-CDR1 containing the amino acid sequence SEQ ID NO:86, LC-CDR2 containing the amino acid sequence SEQ ID NO:101, and LC-CDR3 containing the amino acid sequence SEQ ID NO:112. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0356] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:30, HC-CDR2 comprising the amino acid sequence SEQ ID NO:50, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:67; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:87, LC-CDR2 comprising the amino acid sequence SEQ ID NO:102, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:113. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0357] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:31, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:68; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0358] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:32, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:69; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0359] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:33, HC-CDR2 comprising the amino acid sequence SEQ ID NO:52, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:70; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:89, LC-CDR2 comprising the amino acid sequence SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:115. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0360] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:34, HC-CDR2 comprising the amino acid sequence SEQ ID NO:53, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:71; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0361] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:35, HC-CDR2 comprising the amino acid sequence SEQ ID NO:54, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:72; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:90, LC-CDR2 comprising the amino acid sequence SEQ ID NO:105, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:116. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0362] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:36, HC-CDR2 comprising the amino acid sequence SEQ ID NO:55, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:73; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:117. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0363] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:37, HC-CDR2 comprising the amino acid sequence SEQ ID NO:56, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:74; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:117. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0364] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:31, HC-CDR2 comprising the amino acid sequence SEQ ID NO:57, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:75; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:92, LC-CDR2 comprising the amino acid sequence SEQ ID NO:107, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:118. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0365] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:38, HC-CDR2 comprising the amino acid sequence SEQ ID NO:58, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:76; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:93, LC-CDR2 comprising the amino acid sequence SEQ ID NO:108, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:119. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0366] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing the amino acid sequence SEQ ID NO:39, HC-CDR2 containing the amino acid sequence SEQ ID NO:51, and HC-CDR3 containing the amino acid sequence SEQ ID NO:77; and b) a light chain variable domain comprising: LC-CDR1 containing the amino acid sequence SEQ ID NO:88, LC-CDR2 containing the amino acid sequence SEQ ID NO:103, and LC-CDR3 containing the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0367] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:40, HC-CDR2 comprising the amino acid sequence SEQ ID NO:59, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:78; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:94, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:121. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0368] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:41, HC-CDR2 comprising the amino acid sequence SEQ ID NO:60, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:79; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0369] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:42, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0370] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:42, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0371] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:43, HC-CDR2 comprising the amino acid sequence SEQ ID NO:61, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:81; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:122. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0372] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:44, HC-CDR2 comprising the amino acid sequence SEQ ID NO:62, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:82; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:96, LC-CDR2 comprising the amino acid sequence SEQ ID NO:110, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:123. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0373] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing the amino acid sequence SEQ ID NO:45, HC-CDR2 containing the amino acid sequence SEQ ID NO:63, and HC-CDR3 containing the amino acid sequence SEQ ID NO:83; and b) a light chain variable domain comprising: LC-CDR1 containing the amino acid sequence SEQ ID NO:97, LC-CDR2 containing the amino acid sequence SEQ ID NO:104, and LC-CDR3 containing the amino acid sequence SEQ ID NO:124. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0374] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 containing the amino acid sequence SEQ ID NO:46, HC-CDR2 containing the amino acid sequence SEQ ID NO:53, and HC-CDR3 containing the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 containing the amino acid sequence SEQ ID NO:98, LC-CDR2 containing the amino acid sequence SEQ ID NO:103, and LC-CDR3 containing the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0375] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:47, HC-CDR2 comprising the amino acid sequence SEQ ID NO:64, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:84; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:99, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:125. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0376] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG1 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:43, HC-CDR2 comprising the amino acid sequence SEQ ID NO:61, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:81; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:126. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21, and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0377] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:3, and HC-CDR3 comprising amino acid sequence SEQ ID NO:5; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:7, LC-CDR2 comprising amino acid sequence SEQ ID NO:9, and LC-CDR3 comprising amino acid sequence SEQ ID NO:11. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0378] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:4, and HC-CDR3 comprising amino acid sequence SEQ ID NO:6; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:8, LC-CDR2 comprising amino acid sequence SEQ ID NO:10, and LC-CDR3 comprising amino acid sequence SEQ ID NO:12. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0379] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:28, HC-CDR2 comprising the amino acid sequence SEQ ID NO:48, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:65; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:85, LC-CDR2 comprising the amino acid sequence SEQ ID NO:100, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:111. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0380] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:29, HC-CDR2 comprising the amino acid sequence SEQ ID NO:49, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:66; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:86, LC-CDR2 comprising the amino acid sequence SEQ ID NO:101, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:112. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0381] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:30, HC-CDR2 comprising the amino acid sequence SEQ ID NO:50, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:67; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:87, LC-CDR2 comprising the amino acid sequence SEQ ID NO:102, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:113. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0382] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:31, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:68; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0383] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:32, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:69; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0384] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:33, HC-CDR2 comprising the amino acid sequence SEQ ID NO:52, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:70; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:89, LC-CDR2 comprising the amino acid sequence SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:115. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0385] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:34, HC-CDR2 comprising the amino acid sequence SEQ ID NO:53, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:71; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0386] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:35, HC-CDR2 comprising the amino acid sequence SEQ ID NO:54, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:72; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:90, LC-CDR2 comprising the amino acid sequence SEQ ID NO:105, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:116. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0387] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:36, HC-CDR2 comprising the amino acid sequence SEQ ID NO:55, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:73; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:117. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0388] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:37, HC-CDR2 comprising the amino acid sequence SEQ ID NO:56, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:74; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:117. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0389] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:31, HC-CDR2 comprising the amino acid sequence SEQ ID NO:57, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:75; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:92, LC-CDR2 comprising the amino acid sequence SEQ ID NO:107, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:118. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0390] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:38, HC-CDR2 comprising the amino acid sequence SEQ ID NO:58, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:76; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:93, LC-CDR2 comprising the amino acid sequence SEQ ID NO:108, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:119. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0391] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:39, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:77; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0392] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:40, HC-CDR2 comprising the amino acid sequence SEQ ID NO:59, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:78; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:94, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:121. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0393] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:41, HC-CDR2 comprising the amino acid sequence SEQ ID NO:60, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:79; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0394] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:42, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0395] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:42, HC-CDR2 comprising the amino acid sequence SEQ ID NO:51, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:120. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0396] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:43, HC-CDR2 comprising the amino acid sequence SEQ ID NO:61, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:81; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:122. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0397] In some embodiments, a full-length anti-Nogo-A antibody comprising a constant region of IgG4 is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:44, HC-CDR2 comprising the amino acid sequence SEQ ID NO:62, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:82; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:96, LC-CDR2 comprising the amino acid sequence SEQ ID NO:110, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:123. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0398] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:45, HC-CDR2 comprising the amino acid sequence SEQ ID NO:63, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:83; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:97, LC-CDR2 comprising the amino acid sequence SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:124. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0399] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:46, HC-CDR2 comprising the amino acid sequence SEQ ID NO:53, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:80; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:98, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:114. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0400] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:47, HC-CDR2 comprising the amino acid sequence SEQ ID NO:64, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:84; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:99, LC-CDR2 comprising the amino acid sequence SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:125. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0401] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:43, HC-CDR2 comprising the amino acid sequence SEQ ID NO:61, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:81; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:126. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0402] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149; and a light chain variable domain (V L ), the V LThe IgG1 comprises the amino acid sequence shown in any of SEQ ID NOs:18-20, 150-171, or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence shown in any of SEQ ID NOs:18-20, 150-171. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0403] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG2 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149; and a light chain variable domain (V L ), the V L The IgG2 comprises any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171, or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0404] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG3 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (VH ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149; and a light chain variable domain (V L ), the V L The IgG3 comprises any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171, or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0405] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149 or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:13-17, 127-149; and a light chain variable domain (V L ), the V LThe IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171, or variants thereof, wherein the variants have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:18-20, 150-171. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0406] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:13-17 and 127-149, and a light chain variable domain (V L ), the V L The IgG1 comprises any of the amino acid sequences shown in SEQ ID NOs:18-20 and 150-171. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0407] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the VH Contains any of the amino acid sequences shown in SEQ ID NOs:13-17 and 127-149, and a light chain variable domain (V L ), the V L The IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:18-20 and 150-171. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:22 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0408] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V H It comprises the amino acid sequence SEQ ID NO:13 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:13; and V L It comprises the amino acid sequence SEQ ID NO:18 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:18. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0409] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V HIt comprises the amino acid sequence SEQ ID NO:14 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:14; and V L It comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0410] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V H It comprises the amino acid sequence SEQ ID NO:15 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:15; and V L It comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0411] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V HIt comprises the amino acid sequence SEQ ID NO:16 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:16; and V L It comprises the amino acid sequence SEQ ID NO:19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:19. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0412] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V H It comprises the amino acid sequence SEQ ID NO:17 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:17; and V L It comprises the amino acid sequence SEQ ID NO:20 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence SEQ ID NO:20. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0413] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V HIt comprises the amino acid sequence shown in SEQ ID NO:127 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:127; and V L It comprises the amino acid sequence shown in SEQ ID NO:150 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:150. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0414] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:128 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:128; and V L It comprises the amino acid sequence shown in SEQ ID NO:151 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:151. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24.

[0415] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:128 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:128; and V L It comprises the amino acid sequence shown in SEQ ID NO:150 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO:150. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:21. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:23. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or is composed of th...

Claims

1. An isolated anti-Nogo-A antibody, wherein the anti-Nogo-A antibody comprises: Heavy chain variable structural domain (V H ), the V H Include: Heavy chain complementarity-determining region (HC-CDR) 1, whose amino acid sequence is SEQ ID NO: 1; HC-CDR2, whose amino acid sequence is SEQ ID NO: 3; and HC-CDR3, whose amino acid sequence is SEQ ID NO: 5; and Light chain variable structural domain (V L ), the V L Include: The light chain complementarity-determining region (LC-CDR) 1 has the amino acid sequence SEQ ID NO: 7; LC-CDR2, whose amino acid sequence is SEQ ID NO: 9; and LC-CDR3, whose amino acid sequence is SEQ ID NO:

11.

2. The isolated anti-Nogo-A antibody according to claim 1, comprising: (i) V H Its amino acid sequence is SEQ ID NO: 13 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO: 13; and V L Its amino acid sequence is SEQ ID NO: 18 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence SEQ ID NO: 18; (ii) V H Its amino acid sequence is SEQ ID NO: 14 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO: 14; and V L The amino acid sequence SEQ ID NO: 19 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence SEQ ID NO: 19; (iii) V H Its amino acid sequence is SEQ ID NO: 15 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO: 15; and V L Its amino acid sequence is SEQ ID NO: 19 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO: 19; or (iv) V H Its amino acid sequence is SEQ ID NO: 16 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO: 16; and V L The amino acid sequence is SEQ ID NO: 19 or a variant thereof, the variant having at least 80% sequence identity with the amino acid sequence SEQ ID NO:

19.

3. The isolated anti-Nogo-A antibody according to any one of claims 1-2, wherein the Kd value of the anti-Nogo-A antibody binding to human Nogo-A is 0.1 pM to 10 nM.

4. The isolated anti-Nogo-A antibody according to any one of claims 1-2, wherein the anti-Nogo-A antibody comprises an Fc fragment.

5. The isolated anti-Nogo-A antibody according to claim 4, wherein the anti-Nogo-A antibody is a full-length IgA, IgD, IgE, IgG or IgM antibody.

6. The isolated anti-Nogo-A antibody according to claim 5, wherein the anti-Nogo-A antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.

7. The isolated anti-Nogo-A antibody according to any one of claims 1-2, wherein the anti-Nogo-A antibody is a humanized antibody.

8. The isolated anti-Nogo-A antibody according to any one of claims 1-2, wherein the anti-Nogo-A antibody is a chimeric antibody.

9. The isolated anti-Nogo-A antibody according to any one of claims 1-2, wherein the anti-Nogo-A antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, single-chain Fv (scFv), Fv fragment, double-chain antibody (diabody), and linear antibody.

10. An isolated nucleic acid molecule encoding the anti-Nogo-A antibody according to any one of claims 1-9.

11. A carrier comprising the nucleic acid molecule of claim 10.

12. An isolated host cell comprising the nucleic acid molecule of claim 10 or the vector of claim 11.

13. A method for preparing anti-Nogo-A antibody, comprising: a) Culture host cells containing the vector of claim 11 under conditions that enable efficient expression of anti-Nogo-A antibody; and b) Obtain expressed anti-Nogo-A antibodies from host cells.

14. A pharmaceutical composition comprising an anti-Nogo-A antibody according to any one of claims 1-9, a nucleic acid molecule according to claim 10, a carrier according to claim 11, an isolated host cell according to claim 12 or an antibody prepared by the method according to claim 13, and a pharmaceutically acceptable carrier.

15. Use of the antibody of any one of claims 1-9, the nucleic acid molecule of claim 10, the vector of claim 11, the host cell of claim 12, the antibody prepared by the method of claim 13, or the pharmaceutical composition of claim 14 in the preparation of a medicament for treating spinal cord injury.

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