Antibody for specifically recognizing Nogo-A and application thereof

Abstract

Relates to an antibody or an antigen binding fragment capable of specifically recognizing Nogo-A, and a preparation method and application of the antibody or the antigen binding fragment.

Description

Antibodies specifically recognizing Nogo-A and their applications

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese patent application number 202211006418.4, application date 2022.08.22, and invention name “Antibodies specifically recognizing Nogo-A and their applications”, and the entire contents of that application are incorporated herein by reference.

[0003] Submit electronic sequence listing as XML file

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

[0005] The present invention relates to antibodies that specifically recognize NogoA, as well as preparation methods and uses thereof, including methods of using the antibodies to treat diseases and / or conditions caused by Nogo-A signaling pathway disorders, such as central nervous system and / or peripheral nervous system diseases or trauma. Background Art

[0006] After injury to the adult central nervous system (CNS), nerve regeneration is limited by the inhibitory myelin environment surrounding axons and the formation of scar tissue. Studies have shown that factors that inhibit nerve growth significantly affect the regenerative capacity of the adult CNS after injury. These factors play an important role in stabilizing the complex wiring of the adult higher vertebrate CNS and establishing neuronal pathways during nervous system development (Akbik FV et al. Exp Neurol. 2012; Schwab ME et al. Nat Rev Neurosci. 2010). Molecules such as Nogo-A, myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein (OMGP) have been described as potent neurite inhibitors.

[0007] One of the most studied inhibitory factors is Nogo-A, a member of the plasma membrane protein family. It is expressed in myelin and certain neurons, inhibiting axonal regeneration and plasticity after 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 a functional receptor for the Nogo-A Δ20 domain (Kempf A et al. PLoS Biol. 2014).

[0008] Nogo-A binds to the receptor NgR1 through its inhibitory Nogo-66 domain and forms a complex with the transmembrane protein LINGO1, p75 or TROY, thereby inhibiting neurite outgrowth. This binding leads to intracellular Ca 2+ Nogo-66 is a key regulator of growth and development, and it is associated with increased expression 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). RhoA signaling destabilizes the actin cytoskeleton, 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, with three distinct expression windows during development (Huber et al., Trends Cell Biol, 2007; Wang, X et al., J. Neurosci. 2002). First, during 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 phase of central and peripheral neurons, Nogo-A is expressed in a variety of neuronal types, particularly those with long axons. This expression decreases after birth to low levels that are generally undetectable. 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 types of neurons are characterized by a high degree of plasticity in their 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 types (Schwann cells) in the peripheral nervous system do not express Nogo-A (Huber et al., J. Neurosci, 2002). Outside the central nervous system, Nogo-A is expressed in developing skin, skeletal muscle during differentiation, and heart. Cardiac tissue in adult rats, mice, and humans, as well as certain immune cells in mice and humans, particularly macrophages, express Nogo-A and components of the Nogo receptor complex, such as NgR1.

[0010] In Nogo-A-deficient mice, spinal cord extracts have a reduced inhibitory effect on neurite outgrowth in the deficient 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 toward the lesion site compared to wild-type mice. This study shows that systemic deletion of the myelin-related growth inhibitor Nogo-A can improve regeneration and plasticity responses after spinal cord injury (M Simonen et al., Neuron, 2003). In addition, it has been shown that neutralizing Nogo-A can promote axonal growth and compensatory sprouting in the adult spinal cord and brain, and can improve functional recovery after central nervous system injury (Schwab ME et al. Curr Opin Neurobiol. 2004.; Kempf et al. Physiology. 2013.). Recent studies have revealed a novel and important role for Nogo-A signaling in inhibiting synaptic plasticity in mature neuronal networks, suggesting that Nogo-A's inhibitory potential extends far beyond its previously investigated role in limiting 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 effects on axonal regeneration in the adult central nervous system, researchers have also found that Nogo-A regulates the migration of neural precursors in the embryonic mouse cortex. Cortical neural precursor migration is enhanced in Nogo-A- / - mice and in wild-type neurons cultured in the presence of anti-Nogo-A, NgR1, or LINGO-1 antibodies, suggesting that cell-surface Nogo-A regulates neuronal migration in the early developing CNS through the NgR1-LINGO1 receptor complex (Mathis, C et al., Cereb Cortex, 2010).

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

[0012] Therefore, there is still a need in the art for therapeutic antibodies that 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 the like.

[0013] The disclosures of all publications, patents, patent applications, and published patent applications mentioned herein are incorporated 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 The heavy chain complementarity determining region (HC-CDR) 1 comprises DYGMH (SEQ ID NO: 1); HC-CDR2 comprises SISHTGKTVFYGESVKG (SEQ ID NO: 3); and HC-CDR3 comprises TELGGDNWFDV (SEQ ID NO: 5); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising TGSSSNIGGYDVY (SEQ ID NO: 7); a LC-CDR2 comprising DNNKRPS (SEQ ID NO: 9); and a LC-CDR3 comprising AAWDDSLYGYI (SEQ ID NO: 11).

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

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

[0018] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 13 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 18 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (ii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 14 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 15 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iv) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 16 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Contains 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 Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0020] In some embodiments, any of the isolated anti-Nogo-A antibodies described above comprises: V H , comprising an amino acid sequence as shown in any one of SEQ ID NOs: 13-16 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 13-16; and V L , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 18-19 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs: 18-19.

[0021] In some embodiments, an isolated anti-Nogo-A antibody is provided comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 13 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 13; and V L , comprising the amino acid sequence of SEQ ID NO: 18 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 18; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 14 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 14; and V L , comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19; (iii) V H, comprising the amino acid sequence of SEQ ID NO: 15 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 15; and V L , comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 16 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 16; and V L , comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19.

[0022] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 17 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 20 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0024] In some embodiments, any of the isolated anti-Nogo-A antibodies described above comprises: V H, comprising the amino acid sequence of SEQ ID NO: 17 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 17; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 20 or a variant thereof, wherein the variant has 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 The heavy chain complementarity determining region (HC-CDR) 1 comprises SYGMH (SEQ ID NO: 28); HC-CDR2 comprises VIWYHGSKKYYADSVKD (SEQ ID NO: 48); and HC-CDR3 comprises SIAETTDYGLDS (SEQ ID NO: 65); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLLYRGGKTFLY (SEQ ID NO: 85); a LC-CDR2 comprising ELSNRAS (SEQ ID NO: 100); and a LC-CDR3 comprising MQGIQLPWT (SEQ ID NO: 111).

[0026] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof, wherein the variant comprises at most about 3 amino acid substitutions; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 85 or a variant thereof, wherein the variant comprises 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, wherein the variant comprises 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, wherein the variant comprises 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 Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 127-128 H Contains HC-CDR1, HC-CDR2 and HC-CDR3, as well as V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 150-151 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0028] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 127 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 150 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (ii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 128 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 151 L Containing LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 128 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 150 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or the VH A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 100, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 111, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0030] In some embodiments, any of the isolated anti-Nogo-A antibodies described above comprises: V H , comprising an amino acid sequence as shown in any one of SEQ ID NOs: 127-128 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence as shown in any one of SEQ ID NOs: 127-128; and V L , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 150-151 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in any one of SEQ ID NOs: 150-151.

[0031] In some embodiments, an isolated anti-Nogo-A antibody is provided comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 127; and V L , comprising the amino acid sequence of SEQ ID NO: 150 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 150; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , comprising the amino acid sequence of SEQ ID NO: 151 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 151; (iii) V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L, comprising the amino acid sequence of SEQ ID NO: 150 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 150.

[0032] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 129 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 152 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 86, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 101, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 112, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0034] In some embodiments, any of the isolated anti-Nogo-A antibodies described above comprises: V H , comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 129; and V L , which comprises the amino acid sequence shown in SEQ ID NO: 152 or a variant thereof, wherein the variant has 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 H, which comprises V as shown in the amino acid sequence SEQ ID NO: 130 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 153 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 87, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0038] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 131 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 154 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0041] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 132 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 155 L Contains 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 Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 32, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0044] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 133 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 156 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 89, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 115, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0047] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 134 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 157 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0050] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 135 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 158 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 72, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 90, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 116, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0053] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 136 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 159 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0056] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 137H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 159 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0059] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 138 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 160 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 92, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 107, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 118, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0062] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 139 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 161 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 58, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, or the VH A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 93, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 119, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0065] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 162 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0068] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 141 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 163 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 94, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 121, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0071] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 164 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 60, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0074] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 143 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 165 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0077] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 144H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 166 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 122, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0080] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 145 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 167 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 96, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 110, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0083] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 146 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 168 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83, or the VH A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 97, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 124, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0086] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 147 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 169 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 98, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0089] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 148 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 170 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 125, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0092] In some embodiments, an isolated anti-Nogo-A antibody is provided, comprising: (i) V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 149 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 171 L Contains 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 comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0095] In some embodiments, the isolated anti-Nogo-A antibody binds to human Nogo-A with a Kd value of 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 above isolated anti-Nogo-A antibodies 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 above isolated anti-Nogo-A antibodies.

[0097] In some embodiments, any of the isolated anti-Nogo-A antibodies 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 the group consisting of 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, encoding any of the anti-Nogo-A antibodies described above. In some embodiments, a vector is provided, comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, 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 of producing an anti-Nogo-A antibody is provided, comprising: a) culturing any of the host cells described above under conditions effective to express the anti-Nogo-A antibody; and b) obtaining the expressed anti-Nogo-A antibody from the host cell.

[0099] In some embodiments, a method of treating a disease or condition in a subject in need thereof is provided, comprising administering to the subject an effective amount of any of the anti-Nogo-A antibodies described above. In some embodiments, use of any of the anti-Nogo-A antibodies described above in the preparation of a pharmaceutical composition for treating a disease or condition in a subject in need thereof is provided. In some embodiments, 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 associated with the Nogo-A signaling pathway, including a disease or injury or condition 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 diseases of the cranium, brain or spinal cord, stroke, demyelinating diseases such as multiple sclerosis, monophasic demyelination, encephalomyelitis, multifocal leukoencephalitis, panencephalitis, Marchiafava-Bignami disease, pontine myelmolysis, adrenoleukodystrophy, Pelitzowitz-Merzbacher disease, spongiform encephalopathy, subacute myelopathy, ... Alexandra disease, spongiform degeneration of the white matter, metachromatic leukodystrophy and Krabbe's disease, degenerative visual diseases such as general ischemic retinopathy, anterior ischemic optic neuropathy, optic neuritis, age-related macular degeneration, diabetic retinopathy, cystic macular edema (CME), retinitis pigmentosa, Šgurdsson disease, Best's vitelliform retinal degeneration, Leber's congenital amaurosis and other hereditary retinal degenerations, pathological myopia, retinopathy of prematurity and Leber's hereditary optic neuropathy, psychiatric diseases such as schizophrenia and depression.

[0100] Also provided are pharmaceutical compositions, kits, and manufactured products comprising any of the anti-Nogo-A antibodies described above. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0102] Figure 2 shows the inhibitory activity of anti-Nogo-A antibodies against the binding of hNiG to Nogo-A receptors on cell membranes as analyzed by ELISA. Figure 2A shows the inhibitory activity of exemplary antibodies L82, H-L82-1, H-L82-2, and H-L82-3 against the binding of hNiG to Nogo-A receptors on PC12 cell membranes as analyzed by ELISA. Figure 2B shows the inhibitory activity of exemplary antibodies L82, H-L82-1, H-L82-2, and H-L82-3 against the binding of hNiG to Nogo-A receptors on 3T3 cell membranes as analyzed by ELISA.

[0103] Figure 3 shows the cross-binding activity of anti-Nogo-A antibodies with Nogo-A from different species, including human, rhesus monkey, rat, and mouse, as analyzed by FACS. Figure 3A shows the binding activity of anti-Nogo-A antibodies mkNG-22, L82, H-L82-1, H-L82-2, and H-L82-3 with human Nogo-A as analyzed by FACS. Figure 3B 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 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. FIG3D 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 shows the blocking activities of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3 and mkNG-22 on Nogo-A inhibition of GAP-43 transcription levels as analyzed by relative fluorescence quantitative PCR.

[0105] Figure 5 shows the restorative effect of anti-Nogo-A antibodies on hNiG-inhibited neurite outgrowth in N1E-115 cells. Figure 5A shows the restorative effect of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3, and mkNG-22 on the morphology of hNiG-inhibited neurite outgrowth in N1E-115 cells, as observed by microscopy. Figure 5B shows the restorative effect of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3, and mkNG-22 on the ratio of hNiG-inhibited neurite outgrowth in N1E-115 cells, as analyzed by quantitative analysis. Figure 5C shows the restorative effect of anti-Nogo-A antibody mkNG-362 on the ratio of hNiG-inhibited neurite outgrowth in N1E-115 cells, as analyzed by quantitative analysis.

[0106] Figure 6 shows the restorative effect of anti-Nogo-A antibodies on the inhibition of neurite outgrowth in N1E-115 cells by monkey spinal cord extract. Figure 6A shows the restorative effect of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3, and mkNG-22 on the morphology of neurite outgrowth in N1E-115 cells inhibited by monkey spinal cord extract, as observed by microscopy. Figure 6B shows the restorative effect of anti-Nogo-A antibodies L82, H-L82-1, H-L82-2, H-L82-3, and mkNG-22 on the morphology of neurite outgrowth in N1E-115 cells inhibited by monkey spinal cord extract, as analyzed by quantitative analysis. Figure 6C shows the restorative effect of exemplary anti-Nogo-A antibodies mkNG-360 and mkNG-362 on the morphology of neurite outgrowth in PC12 cells inhibited by hNiG, as analyzed by quantitative analysis.

[0107] FIG. 7 shows that the exemplary anti-Nogo-A antibody H-L82-3 has the effect of treating spinal cord injury in a spinal cord injury mouse model.

[0108] Detailed description of this application

[0109] In one aspect, the present application provides anti-Nogo-A antibody molecules. 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, highly effective antibody molecules capable of binding to human Nogo-A and inhibiting the interaction of human Nogo-A with its receptor have been identified. The results presented herein demonstrate that the antibodies of the present application bind to Nogo-A more effectively than the known anti-Nogo-A antibodies ATI-355 or 11C7 (Novartis), and surprisingly, in various biological experiments, the antibodies of the present application have been shown to be even more potent than ATI-355.

[0110] The anti-Nogo-A antibodies provided herein 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, the present application provides an anti-Nogo-A antibody, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V HThe heavy chain complementarity determining region (HC-CDR) 1 comprises DYGMH (SEQ ID NO: 1); HC-CDR2 comprises SISHTGKTVFYGESVKG (SEQ ID NO: 3); and HC-CDR3 comprises TELGGDNWFDV (SEQ ID NO: 5); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising TGSSSNIGGYDVY (SEQ ID NO: 7); a LC-CDR2 comprising DNNKRPS (SEQ ID NO: 9); and a LC-CDR3 comprising AAWDDSLYGYI (SEQ ID NO: 11).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0127] On the other hand, the present application provides an anti-Nogo-A antibody, wherein the anti-Nogo-A antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SYYIQ (SEQ ID NO: 41); HC-CDR2 comprises RINPKTGGTNFAQKFQG (SEQ ID NO: 60); and HC-CDR3 comprises GVAAASY (SEQ ID NO: 79); and a light chain variable domain (V L ), the V L It comprises a light chain complementary determining region (LC-CDR) 1 comprising KSSQSLLYSSNNKNYLA (SEQ ID NO: 88); a LC-CDR2 comprising WASTRES (SEQ ID NO: 103); and a LC-CDR3 comprising QQYYSTPLT (SEQ ID NO: 114).

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

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

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

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

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

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

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

[0135] Also provided are nucleic acids encoding anti-Nogo-A antibodies, compositions comprising anti-Nogo-A antibodies, and methods of making and using anti-Nogo-A antibodies.

[0136] definition

[0137] As used herein, "treatment" or "treating" is a method of obtaining beneficial or desired results, including clinical results. For the purposes of this application, the beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, improving the disease state, alleviating the disease (partially or completely), reducing the dose of one or more other drugs required to treat the disease, delaying the progression of the disease, improving or enhancing the quality of life, increasing body weight, and / or prolonging survival. At the same time, "treatment" also includes a reduction in the pathological consequences of the disease (e.g., inhibition of neurite outgrowth in the case of neural damage). The methods of the present application contemplate any one or more aspects of these treatments.

[0138] The term "antibody" includes full-length antibodies and antigen-binding fragments thereof. Full-length antibodies include two heavy chains and two light chains. The variable regions of 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, and 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 by the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). The three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more highly conserved than the CDR regions and form a scaffold that supports the hypervariable loops. The constant regions of the heavy and light chains are not involved in antigen binding but exhibit various effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by having heavy chains of type α, δ, ε, γ, and μ, respectively. Several major antibody classes are divided into subclasses, 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 used herein, the term "antigen-binding fragment" includes antibody fragments, such as diabodies, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabodies (dsdiabodies), single-chain Fv (scFv), scFv dimers (divalent diabodies), multispecific antibodies composed of antibody fragments comprising one or more CDRs, single-domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragment that can bind to an antigen but does not contain a complete antibody structure. Antigen-binding fragments can bind to the same antigen as a parent antibody or parent antibody fragment (such as a parent scFv). Antigen-binding fragments also include fusion proteins comprising the above-mentioned antibody fragments. In some embodiments, an antigen-binding fragment may include one or more CDRs from a specific human antibody that are transplanted to a framework region from one or more different human antibodies.

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

[0141] As used herein, a first antibody "competes" for binding to a Nogo-A target with a second antibody when the first antibody, at equimolar concentrations, inhibits 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%), and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody "epitope binning" method based on cross-competition.

[0142] As used herein, the terms "specifically bind," "specifically recognize," or "specific for" refer to a measurable and reproducible interaction, e.g., binding of an antibody to a target that can confirm the presence of the target in a heterogeneous population of molecules, including biomolecules. For example, an antibody that specifically recognizes a target (which may be an epitope) means that the antibody binds to the target with greater affinity, avidity, more readily, and / or more persistently than it binds to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with an affinity that is at least 10 times greater than its binding affinity to other targets.

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

[0144] As used herein, the term "isolated nucleic acid" refers to a nucleic acid of genomic, cDNA, or synthetic origin, or a combination thereof. Depending on its origin, the "isolated nucleic acid" is (1) unrelated to all or part of the polynucleotide sequence found in nature, (2) operably linked to a polynucleotide sequence with which it is not naturally associated, or (3) not found in nature as part of a longer sequence.

[0145] As used herein, the term "CDR" or "complementarity determining region" refers to the non-contiguous antigen binding sites 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 are described in, for example, Desmond et al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlap or subsets of amino acid residues when compared to one another. However, any definition used to designate a CDR of an antibody, grafted antibody, or variant thereof is included within the scope of the term as defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the various references cited above for comparison. Algorithms and binding interfaces for CDR prediction are known in the art, including, for example, 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 contents of the references cited in this paragraph are incorporated herein by reference in their entirety for use in this application and in one or more claims that may be included in this article.

[0146] Table 1: CDR definitions

[0147] 1The amino acid residue numbers refer to the nomenclature of Kabat et al.

[0148] 2 The amino acid residue numbers refer to the nomenclature of Chothia et al.

[0149] 3 The amino acid residue numbers refer to the nomenclature of MacCallum et al.

[0150] 4 The amino acid residue numbers refer to the nomenclature of Lefranc et al.

[0151] 5 The amino acid residue numbers refer to the nomenclature of Honegger and Plückthun.

[0152] 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 class or subclass, while the remainder of the chain(s) is identical or homologous to the corresponding sequence in an antibody from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they have the biological activity described in the present application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)).

[0153] "Fv" is the smallest antibody fragment that contains 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 non-covalently linked. Six hypervariable loops (3 loops each in the light chain and heavy chain) are derived from the folding of these two domains. The hypervariable loops provide the antibody with amino acid residues for binding to the antigen and confer specificity for binding to the antibody. However, even a single variable domain (or half of an Fv fragment, which only contains 3 CDRs specific for the antigen) has the ability to recognize and bind to the antigen, although its affinity is lower than that of the complete binding site.

[0154] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a Fv that contains V molecules linked into a single polypeptide chain. H and V L In some embodiments, the scFv polypeptide further comprises a V H and V LThe linker polypeptide between the domains allows the 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).

[0155] The term "diabody" is used in V H and V L A small antibody fragment is prepared by constructing scFv fragments (see above) using short linkers (e.g., 5-10 residues) between the domains. This allows the variable domains to pair between chains rather than within the chain, resulting in a bivalent fragment, that is, a fragment with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" scFv fragments, in which the V domains of the two antibodies are H and V L The domains are located on different polypeptide chains. Diabodies are fully described in EP 404,097; WO 93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0156] The "humanized" form of a non-human (such as a rodent) antibody is a chimeric antibody that includes minimal sequences from a non-human antibody. In most cases, a humanized antibody is a human immunoglobulin (recipient antibody) in which the hypervariable region (HVR) residues of the recipient antibody are replaced by hypervariable region residues from a non-human species such as a mouse, rat, rabbit or non-human mammal with ideal antibody specificity, affinity and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. In addition, a humanized antibody may include residues that are not present in either the recipient antibody or the donor antibody. These modifications can further improve the performance of the antibody. Typically, a humanized antibody will comprise substantially all, at least one, and usually two variable domains, wherein 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. The human antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically a constant region of a human immunoglobulin. For details, see 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).

[0157] The "percent (%) amino acid sequence identity" or "homology" of the polypeptide and antibody sequences identified herein is defined as the percentage of identical amino acid residues in a candidate sequence and the polypeptide sequence being compared, when the sequences are aligned, considering conservative substitutions as part of the sequence identity. Percent amino acid sequence identity can be determined by various alignment methods within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm needed to maximize alignment over the full length of the sequences being compared. However, for the purposes of this article, percent amino acid sequence identity values ​​are 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).

[0158] The term "Fc receptor" or "FcR" is used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, the FcR described herein is an FcR that binds to an IgG antibody (a gamma receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in the cytoplasmic domain. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) (see M.in Annu. Rev. Immunol. 15:203-234 (1997). The term also includes allotypes, such as the 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). The term FcR in this application encompasses other types of FcRs, including those identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0159] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC) and consists 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 immunoglobulins (IgGs) from mother to newborn and in regulating serum IgG levels. As a salvage receptor, FcRn can bind and transport endocytosed IgGs in their intact form within and between cells, protecting them from the default degradation pathway.

[0160] The "CH1 domain" of a human IgG heavy chain constant region typically stretches from amino acid 118 to amino acid 215 (EU numbering system).

[0161] The "hinge region" is generally defined as stretching from Glu 216 to Pro 230 of human IgG1 (Burton, Molec. Immunol. 22: 161-206 (1985)). By placing the first and last cysteine ​​residues that form inter-heavy chain disulfide bonds in the same positions as in IgG1, the hinge regions of other IgG isotypes can be aligned with the IgG1 sequence.

[0162] The "CH2 domain" of the human IgG Fc region typically extends from amino acids 231 to 340. The CH2 domain is unique in that it does not closely pair with another domain. Instead, two N-terminally linked branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is hypothesized that carbohydrates may serve as a substitute for domain-to-domain pairing, helping to maintain CH2 domain stability. Burton, Molec. Immunol. 22:161-206 (1985).

[0163] The "CH3" domain includes the CH2 domain extending from the C-terminal residue within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, usually amino acid residue 446 or 447 in IgG).

[0164] A "functional Fc fragment" possesses the "effector functions" of a native Fc region sequence. Exemplary "effector functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (e.g., B cell receptor; BCR). Such effector functions generally require the Fc region to be bound to a binding domain (e.g., an antibody variable region) and can be assessed using a variety of experimental methods known in the art.

[0165] IgG Fc variant antibodies with "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and / or ADCC activity compared to the parent polypeptide or a polypeptide comprising a native Fc sequence. Fc variants that exhibit "enhanced binding" to FcRs have a higher binding affinity (e.g., lower apparent Kd or IC) to at least one FcR compared to the parent polypeptide or a polypeptide comprising a native IgG Fc sequence. 50In some embodiments, the binding capacity is enhanced by 3-fold, e.g., 5-, 10-, 25-, 50-, 60-, 100-, 150-, 200-, or even up to 500-fold, or the binding capacity is increased by 25% to 1000%, compared to the parent polypeptide. An Fc variant that exhibits "reduced binding" to an FcR has a lower affinity for at least one FcR (e.g., a higher apparent Kd or IC) than the parent polypeptide. 50 Compared with the parent polypeptide, its binding capacity is reduced by 40% or more.

[0166] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" is a form of cytotoxicity that refers to the binding of secreted Ig to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages), enabling these cytotoxic effector cells to specifically bind to target cells bearing antigen and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are required for this killing. Of the major cell types that mediate 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). To assess the ADCC activity of a target molecule, an in vitro ADCC assay can be performed, as described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, or in addition, the ADCC activity of the target molecule can also be assessed in vivo, for example, as described in the animal model disclosed in Clynes et al. PNAS (USA) 95: 652-656 (1998).

[0167] Polypeptides comprising Fc region variants exhibit "enhanced ADCC activity" or are capable of more effectively mediating ADCC in the presence of human effector cells, compared to polypeptides comprising wild-type IgG Fc polypeptides or parent polypeptides. When tested in substantially the same quantity as polypeptides comprising wild-type IgG Fc polypeptides (or parent polypeptides), such polypeptides comprising Fc region variants are capable of more effectively mediating ADCC, both in vitro and in vivo. Such variants are generally identified using any in vitro ADCC assay known in the art, such as assays or methods for identifying ADCC activity, such as in animal models. In some embodiments, such variants mediate ADCC 5- to 100-fold more efficiently, such as 25- to 50-fold more efficiently, than wild-type Fc (or parent polypeptide).

[0168] "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 (Clq) to an antibody (of the appropriate structural subclass) that binds to the cognate antigen. To assess complement activation, a CDC assay, such as that described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), can be performed. Polypeptide variants with altered Fc region amino acid sequences and increased or decreased Clq binding capacity are described in U.S. Patent No. 6,194,551 Bl 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).

[0169] Unless otherwise indicated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and encode the same amino acid sequence. A nucleotide sequence encoding a protein or RNA may also include introns, for example, a nucleotide sequence encoding a protein may contain introns in some forms.

[0170] The term "operably linked" refers to a functional connection between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling expression of the latter. For example, a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence. For example, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, if necessary, can link two protein coding regions in the same reading frame.

[0171] "Homologous" refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same base or amino acid monomer subunit is present at the same position in two compared sequences, for example, adenine is present at the same position in two DNA molecules, then the two DNA molecules are homologous at that position. The percentage homology between two sequences refers to the ratio of the number of matching or homologous positions shared by the two sequences to the total number of positions multiplied by 100. For example, if 6 out of 10 positions in two sequences are matched or homologous, then the homology between the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally speaking, when aligning two sequences, the comparison is performed with the goal of obtaining maximum homology.

[0172] An "effective amount" of an anti-Nogo-A antibody or composition disclosed herein is an amount sufficient to achieve a specific purpose. An "effective amount" can be determined empirically and by known methods relevant to the stated purpose.

[0173] The term "therapeutically effective amount" refers to an amount of the anti-Nogo-A antibody or composition thereof disclosed herein that is effective in treating a disease or symptom of an individual. For example, in the case of spinal cord injury, a therapeutically effective amount of an anti-Nogo-A antibody or composition thereof refers to an amount that can promote (i.e., restore to some extent) the sprouting and regeneration of the injured corticospinal tract (CST); promote (i.e., restore to some extent) the growth of growth cones; promote (i.e., restore to some extent) the regeneration of damaged neurites; reduce (i.e., relieve to some extent) the inhibition of neurite growth; reduce (i.e., relieve to some extent) the inhibition of growth cone growth; and / or alleviate to some extent one or more symptoms of the underlying disease associated with spinal cord injury. In some embodiments, a therapeutically effective amount refers to an amount that can prolong the patient's survival. In some embodiments, a therapeutically effective amount refers to an amount that can improve the patient's progression-free survival.

[0174] As used herein, "pharmaceutically acceptable" or "pharmacologically compatible" refers to a material that is free of biological activity or other undesirable properties, e.g., a material that can be added to a pharmaceutical composition administered to a patient without causing a significant adverse biological reaction, or that does not interact in a deleterious manner with any other component contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicology or manufacturing testing and / or are included in the inactive ingredient guide compiled by the U.S. Food and Drug Administration.

[0175]

[0066] The embodiments of the present application described herein should be understood to include "consisting of" and / or "consisting essentially of" embodiments.

[0176] Reference herein to "about" for a value or parameter includes (and describes) variations of the value or parameter itself. For example, a description involving "about X" includes a description of "X".

[0177] As used herein, reference to "not" a value or parameter generally indicates and describes "other than" a value or parameter. For example, "the method cannot be used to treat type X cancer" means that the method is generally used to treat other types of cancer besides type X cancer.

[0178] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0179] Anti-Nogo-A antibody

[0180] In one aspect, the present application provides anti-human and / or rhesus monkey Nogo-A antibodies 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. In one aspect, the present application provides isolated antibodies that bind to Nogo-A. Contemplated anti-Nogo-A antibodies include, for example, full-length anti-Nogo-A antibodies (e.g., full-length IgG1 or IgG4), anti-Nogo-A single-chain antibodies, anti-Nogo-A Fc fusion proteins, multispecific (e.g., 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 (e.g., full-length IgG1 or IgG4) or an antigen-binding fragment thereof 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, the antibody that specifically binds to Nogo-A refers to an antibody that binds to Nogo-A with an affinity that is at least 10 times greater than the affinity for binding to a non-target (including, for example, 10 ... 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 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 assay (RIA). Kd values ​​can be determined by methods known in the art, such as surface plasmon resonance (SPR) or biolayer interferometry (BLI).

[0181] Although anti-Nogo-A antibodies comprising human sequences (e.g., human heavy and light chain variable domains comprising human CDR sequences) are generally discussed herein, non-human anti-Nogo-A antibodies are also contemplated. In some embodiments, non-human anti-Nogo-A antibodies comprise human CDR sequences of anti-Nogo-A antibodies described herein and non-human framework region sequences. In some embodiments, non-human framework region sequences include 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, buffaloes), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., small apes, macaques), etc. In some embodiments, non-human anti-Nogo-A antibodies include anti-Nogo-A antibodies generated by grafting one or more human CDR sequences described herein into non-human framework regions (e.g., mouse or chicken framework region sequences).

[0182] An exemplary human Nogo-A exon 3-encoded NiG amino acid sequence comprises or consists of the amino acid sequence set forth in SEQ ID NO: 25. An exemplary rhesus monkey NiG amino acid sequence comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26. An exemplary rat NiG amino acid sequence comprises or consists of the amino acid sequence set forth in SEQ ID NO: 27.

[0183] In some embodiments, the anti-Nogo-A antibodies described herein specifically recognize an epitope in human Nogo-A. In some embodiments, the anti-Nogo-A antibodies cross-react with Nogo-A from species other than human. In some embodiments, the anti-Nogo-A antibodies are completely specific for human Nogo-A and do not cross-react with other non-human species.

[0184] 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 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (e.g., conservative substitutions) compared to the naturally occurring Nogo-A protein (or a fragment thereof). 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).

[0185] 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 in cynomolgus monkeys. In some embodiments, the anti-Nogo-A antibody does not cross-react with any interspecies variant of the Nogo-A protein.

[0186] In some embodiments, as described herein, any anti-Nogo-A antibody 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 heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-Nogo-A antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 21. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 22. In some embodiments, the anti-Nogo-A antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 23. In some embodiments, the anti-Nogo-A antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of 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.

[0187] In some embodiments, the anti-Nogo-A antibody comprises a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises DYGMH (SEQ ID NO: 1); HC-CDR2 comprises SISHTGKTVFYGESVKG (SEQ ID NO: 3); and HC-CDR3 comprises TELGGDNWFDV (SEQ ID NO: 5); and a light chain variable domain (V L ), the V LIt comprises: a light chain complementarity determining region (LC-CDR) 1 comprising TGSSSNIGGYDVY (SEQ ID NO: 7); a LC-CDR2 comprising DNNKRPS (SEQ ID NO: 9); and a LC-CDR3 comprising AAWDDSLYGYI (SEQ ID NO: 11).

[0188] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 3 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 5 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids.

[0189] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 3, and HC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 5.

[0190] In some embodiments, the anti-Nogo-A antibody comprises V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 7 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 9 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 11 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0191] In some embodiments, the anti-Nogo-A antibody comprises V L , the V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:7, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:9, and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:11.

[0192] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 7 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 9 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 11 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0193] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:7, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:9, and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:11.

[0194] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0196] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 13-16 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 18-19 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0197] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 13 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L, which comprises V as shown in the amino acid sequence SEQ ID NO: 18 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0198] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 14 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0199] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 15 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0200] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 16 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 19 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0201] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 13-16 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 to the amino acid sequence as set forth in any one of SEQ ID NOs: 13-16; and V L , the V Lcomprising an amino acid sequence as set forth in any one of SEQ ID NOs: 18-19 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 to the amino acid sequence as set forth in any one of SEQ ID NOs: 18-19. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 13-16, and V L , the V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 18-19.

[0202] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 13 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 13; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 18 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 18. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 13, and V L , the V L Comprising the amino acid sequence SEQ ID NO:18.

[0203] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 14 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 14; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 14, and V L , the V L Comprising the amino acid sequence SEQ ID NO:19.

[0204] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 15 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 15; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 15, and V L , the V L Comprising the amino acid sequence SEQ ID NO:19.

[0205] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 16 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 16; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 19. In some embodiments, the anti-Nogo-A antibody comprises V H , the VH Comprising the amino acid sequence SEQ ID NO: 16, and V L , the V L Comprising the amino acid sequence SEQ ID NO:19.

[0206] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0207] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12.

[0208] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 17 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 20 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0209] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 17 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 17; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 17, and V L , the V L Comprising the amino acid sequence SEQ ID NO:20.

[0210] In some embodiments, the anti-Nogo-A antibody comprises a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SYGMH (SEQ ID NO: 28); HC-CDR2 comprises VIWYHGSKKYYADSVKD (SEQ ID NO: 48); and HC-CDR3 comprises SIAETTDYGLDS (SEQ ID NO: 65); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RSSQSLLYRGGKTFLY (SEQ ID NO: 85); a LC-CDR2 comprising ELSNRAS (SEQ ID NO: 100); and a LC-CDR3 comprising MQGIQLPWT (SEQ ID NO: 111).

[0211] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids.

[0212] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:28, HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:48, and HC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:65.

[0213] In some embodiments, the anti-Nogo-A antibody comprises V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 85 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 100 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 111 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0214] In some embodiments, the anti-Nogo-A antibody comprises V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:85, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:100, and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:111.

[0215] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO: 85 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 100 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO: 111 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0216] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:85, LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:100, and LC-CDR3, which comprises the amino acid sequence shown in SEQ ID NO:111.

[0217] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 100, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 111, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

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

[0219] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 127-128 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 150-151 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0220] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 127 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 150 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0221] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 128 HHC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 151 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0222] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 128 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 150 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0223] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of any one of SEQ ID NOs: 127-128 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 to the amino acid sequence of any one of SEQ ID NOs: 127-128; and V L , the V L comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 150-151 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 to the amino acid sequence as set forth in any one of SEQ ID NOs: 150-151. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 127-128, and V L , the V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 150-151.

[0224] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 127; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 150. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 127, and V L , the V L Comprising the amino acid sequence SEQ ID NO:150.

[0225] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 151. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 128, and V L , the V L Comprising the amino acid sequence SEQ ID NO:151.

[0226] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , the VL comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 150. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 128, and V L , the V L Comprising the amino acid sequence SEQ ID NO:150.

[0227] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 86, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 101, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 112, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs

[0228] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:86, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:101, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:112.

[0229] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 129 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 152 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0230] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 129; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 152. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 129, and V L , the V L Comprising the amino acid sequence SEQ ID NO:152.

[0231] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 87, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 113, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0232] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:87, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:102, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:113.

[0233] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 130 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 153 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0234] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 130 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 130; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 153. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 130, and V L , the V L Comprising the amino acid sequence SEQ ID NO:153.

[0235] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0236] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114.

[0237] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 131 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 154 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0238] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 131 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 131; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 154. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 131, and V L , the V L Comprising the amino acid sequence SEQ ID NO:154.

[0239] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 32, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0240] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 32, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114.

[0241] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 132 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 155 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0242] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 132 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 132; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 155. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 132, and V L , the V L Comprising the amino acid sequence SEQ ID NO:155.

[0243] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 89, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 115, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0244] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:89, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:115.

[0245] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 133 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 156 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0246] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 133 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 133; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 156. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 133, and V L , the V L Comprising the amino acid sequence SEQ ID NO:156.

[0247] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0248] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114.

[0249] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 134 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 157 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0250] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 134 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 134; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 157. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 134, and V L , the V L Comprising the amino acid sequence SEQ ID NO:157.

[0251] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 72, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 90, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 116, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0252] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 72; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:90, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:105, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:116.

[0253] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 135 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 158 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0254] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 135 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 135; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 158 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 158. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 135, and V L , the V L Comprising the amino acid sequence SEQ ID NO:158.

[0255] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0256] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:117.

[0257] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 136 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 159 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0258] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 136 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 136; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 159. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 136, and V L , the V L Comprising the amino acid sequence SEQ ID NO:159.

[0259] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0260] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:91, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:106, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:117.

[0261] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 137 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 159 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0262] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 137 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 137; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 159. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 137, and V L , the V L Comprising the amino acid sequence SEQ ID NO:159.

[0263] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 92, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 107, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 118, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0264] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:92, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:107, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:118.

[0265] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 138 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 160 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0266] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 138 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 138; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 160. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 138, and V L , the V L Comprising the amino acid sequence SEQ ID NO:160.

[0267] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 58, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 93, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 119, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0268] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 58, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:93, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:108, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:119.

[0269] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 139 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 161 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0270] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 139 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 139; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 161. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 139, and V L , the V L Comprising the amino acid sequence SEQ ID NO:161.

[0271] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0272] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:120.

[0273] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 162 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0274] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 162. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 140, and V L , the V L Comprising the amino acid sequence SEQ ID NO:162.

[0275] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 94, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 121, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0276] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:94, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:121.

[0277] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 141 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 163 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0278] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 141; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 163. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 141, and V L , the V L Comprising the amino acid sequence SEQ ID NO:163.

[0279] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 60, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0280] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 41, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 60, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114.

[0281] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 164 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0282] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 164. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 142, and V L , the V L Comprising the amino acid sequence SEQ ID NO:164.

[0283] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0284] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:120.

[0285] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 143 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 165 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0286] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 143 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 143; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 165. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 143, and V L , the V L Comprising the amino acid sequence SEQ ID NO:165.

[0287] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 122, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0288] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:122.

[0289] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 144 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 166 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0290] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 144 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 144; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 166. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 144, and V L , the V L Comprising the amino acid sequence SEQ ID NO:166.

[0291] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 96, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 110, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0292] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:96, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:110, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:123.

[0293] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 145 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 167 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0294] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 145 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 145; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 167 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 167. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 145, and V L , the V L Comprising the amino acid sequence SEQ ID NO:167.

[0295] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 97, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 124, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0296] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:97, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:124.

[0297] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 146 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 168 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0298] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 146 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 146; and VL , the V L comprising the amino acid sequence of SEQ ID NO: 168 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 168. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 146, and V L , the V L Comprising the amino acid sequence SEQ ID NO:168.

[0299] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 98, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0300] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:98, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114.

[0301] In some embodiments, the anti-Nogo-A antibody comprises V H, which comprises V as shown in the amino acid sequence SEQ ID NO: 147 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 169 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0302] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 147 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 147; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 169 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 169. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 147, and V L , the V L Comprising the amino acid sequence SEQ ID NO:169.

[0303] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 125, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0304] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:99, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:125.

[0305] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 148 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 170 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0306] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 148 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 148; and V L , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 170. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 148, and V L , the V L Comprising the amino acid sequence SEQ ID NO:170.

[0307] In some embodiments, the anti-Nogo-A antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0308] In some embodiments, the anti-Nogo-A antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:95, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:109, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:126.

[0309] In some embodiments, the anti-Nogo-A antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 149 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 171 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0310] In some embodiments, the anti-Nogo-A antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 149 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 149; and VL , the V L comprising the amino acid sequence of 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 to the amino acid sequence of SEQ ID NO: 171. In some embodiments, the anti-Nogo-A antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 149, and V L , the V L Comprising the amino acid sequence SEQ ID NO:171.

[0311] In some embodiments, the above-mentioned amino acid substitutions are limited to the "exemplary substitutions" shown herein in Table 4. In some embodiments, the amino acid substitutions are limited to the "preferred substitutions" shown herein in Table 4.

[0312] In some embodiments, functional epitopes can be resolved by combinatorial alanine scanning. In this process, combinatorial alanine scanning can be used to identify amino acids in the Nogo-A protein that are essential for interaction with the anti-Nogo-A antibody. In some embodiments, the epitope is conformational and can be identified using a crystal structure of an anti-Nogo-A antibody bound to the Nogo-A protein.

[0313] In some embodiments, the present application provides antibodies that compete with any of the anti-Nogo-A antibodies described herein for binding to Nogo-A. In some embodiments, antibodies are provided that can compete with any of the anti-Nogo-A antibodies described herein for binding to an epitope on Nogo-A. In some embodiments, anti-Nogo-A antibodies are provided that are combined with a V H and V L The anti-Nogo-A antibody molecules bind to the same epitope, wherein the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 13-17, 127-149, and the V L In some embodiments, an anti-Nogo-A antibody is provided, which is combined with a V H and V L The anti-Nogo-A antibody competitively binds to Nogo-A, wherein the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 13-17, 127-149, and the V L It comprises the amino acid sequence shown in any one of SEQ ID NOs: 18-20, 150-171.

[0314] In some embodiments, competition assays can be used to identify monoclonal antibodies that compete with the anti-Nogo-A antibodies described herein for Nogo-A binding. Competition assays can determine whether two antibodies bind to the same epitope by recognizing the same or spatially overlapping epitopes or by competitively inhibiting antigen binding of one antibody to the other. In certain embodiments, such competing antibodies bind to the same epitope as the antibodies described herein. Some exemplary competition assays include, but are not limited to, conventional assays 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 epitopes bound by antibodies are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, each antibody is said to bind to the same epitope if it blocks 50% or more of the binding of the other antibody. In some embodiments, the antibody that competes with the anti-Nogo-A antibodies described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.

[0315] Exemplary anti-Nogo-A antibody sequences are shown in Tables 2 and 3, wherein CDR numbering is performed according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms for predicting the positions of CDRs and defining the variable regions of antibody light and heavy chains. H and / or V L Sequences, but based on prediction algorithms other than those exemplified in the table below, are also within the scope of this application.

[0316] Table 2 Exemplary anti-Nogo-A antibody CDR sequences

[0317] Table 2A Exemplary Anti-Nogo-A Antibody CDR Sequences

[0318] Table 3 Exemplary sequences

[0319] Table 3A Exemplary sequences

[0320] Nogo-A

[0321] The 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 carboxy-terminal reticular homeodomain (RTN). This RTN domain is highly similar to proteins encoded by the other three reticular genes, RTN1, RTN2, and RTN3 (Grand Pre et al., Nature, 2000; Oertle et al., Trends Cell Biol. 2003), and their functions in the nervous system and other organs are largely unknown. The RTN domain of the Nogo protein contains two long hydrophobic segments, each of which is long enough to span the cell membrane twice. They are linked together by a 66-amino acid fragment, which is called Nogo-66 (Grand Pre et al., Nature, 2000). The N-terminal structures of Nogo-A, Nogo-B, and Nogo-C differ significantly, with only Nogo-A being shown to exert potent inhibitory effects in the central nervous system (GrandPre et al., Nature, 2000; Huber et al., J Neurosci, 2002). This suggests that a key functional domain resides in a specific portion of the Nogo-A amino terminus. Screening a library of Nogo-A deletion constructs revealed a region that exhibits inhibitory activity against neurite outgrowth and fibroblast proliferation, designated Nogo-A-Δ20 (Oertle et al., J Neurosci, 2003; Kempf A et al., PLoS Biol., 2014). Furthermore, the carboxy-terminal Nogo-66 domain of Nogo-A has also been shown to possess potent neurite outgrowth inhibitory activity (Fournier et al., Nature, 2001). Although sufficient to exert their inhibitory function, Nogo-A-Δ20 and Nogo-66 were shown to be more active when part of a larger Nogo-A-derived 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).

[0322] Nogo-A receptor

[0323] Nogo-A exerts its inhibitory activity through two distinct extracellular domains, Nogo-A-Δ20 (mouse aa 544-725) and Nogo-66 (mouse aa 1026-1091) (Schwab ME et al., Nat Rev Neurosci. 2010; Oertle T et al., J Neurosci. 2003). The first Nogo receptor to be identified was the glycosylphosphatidylinositol (GPI)-linked leucine-rich repeat (LRR) protein Nogo receptor 1 (NgR1, also known as Nogo-66 receptor and plasmin 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 anchor. NgR1 is connected to the plasma membrane of external neurons through a GPI anchor structure. NgR1 is not expressed in rodents or chicks in the early stages of development, 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 initiates an intracellular signaling cascade by binding to NgR1 through its inhibitory Nogo-66 domain. Because NgR does not contain a transmembrane domain, signal transduction requires that the signal of the NgR / ligand interaction be transduced to the co-receptor p75 or TROY and LINGO1 to form a functional ternary complex, thereby inhibiting the growth of neurites. This binding leads to intracellular Ca 2+ through an unknown intermediate. 2+ Increased expression of NgR1 and activation of the Rho-Rho-related frizzled protein kinase (ROCK) pathway. Through RHOA signaling, the actin cytoskeleton is destabilized, leading to growth cone collapse. 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. NgR1 also binds to the growth-inhibiting myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (OMGP) (Domeniconi, M et al., Neuron, 2002; Wang, KC et al., Nature, 2002).

[0324] 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, either pharmacologically or genetically, blocked the Nogo-A-Δ20-mediated inhibitory effect. The study also demonstrated that Nogo-A-Δ20 binds to S1PR2 via extracellular receptor loops 2 and 3, distinct from the previously described S1P binding site (Hanson MA et al., Sci. 2012). Nogo-A-Δ20 signals through the G protein G13, the leukemia-associated Rho guanine exchange factor (RhoGEF) LARG, and RhoA. Knockout or blockade of S1PR2 abolished the Nogo-A-Δ20- and myelin-mediated inhibition of neuronal outgrowth and cell proliferation. Acute S1PR2 blockade increased long-term synaptic plasticity in the hippocampus and cortex, similar to the effects of Nogo-A neutralization. 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.).

[0325] Full-length anti-Nogo-A antibody

[0326] 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 comprises an IgG constant region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or variants thereof. In some embodiments, the full-length anti-Nogo-A antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti-Nogo-A antibody comprises a kappa 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 comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-Nogo-A antibody comprises 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).

[0327] Thus, for example, in some embodiments, a full-length anti-Nogo-A antibody comprising an IgG1 constant region is provided, wherein the anti-Nogo-A antibody specifically binds to Nogo-A. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0328] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG2 constant region is provided, wherein the anti-Nogo-A antibody specifically binds to Nogo-A. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0329] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG3 constant region is provided, wherein the anti-Nogo-A antibody specifically binds to Nogo-A. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0330] In some embodiments, a full-length anti-Nogo-A antibody comprising an IgG4 constant region is provided, wherein the anti-Nogo-A antibody specifically binds to Nogo-A. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0331] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-2, 28-47 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 3-4, 48-64 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 5-6, 65-84 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 7-8, 85-90 or a variant thereof. 99 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, an LC-CDR2 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 9-10, 100-110 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an LC-CDR3 comprising an amino acid sequence as set forth in any one of SEQ ID NOs: 11-12, 111-126 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24.

[0332] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-2, 28-47 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 3-4, 48-64 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 5-6, 65-84 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs: 7-8, 85-99 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 9-10, 100-110 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 11-12, 111-126 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG2 is a human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0333] 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 as shown in any one of SEQ ID NOs: 1-2, 28-47 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions, HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 3-4, 48-64 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 5-6, 65-84 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:7-8, 85-99 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2, comprising an amino acid sequence as shown in any one of SEQ ID NOs:9-10, 100-110 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3, comprising an amino acid sequence as shown in any one of SEQ ID NOs:11-12, 111-126 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG3 is a human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24.

[0334] 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: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-2, 28-47 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 3-4, 48-64 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 5-6, 65-84 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs: 7-8, 85-99 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, LC-CDR2, which comprises an amino acid sequence as shown in any one of SEQ ID NOs: 9-10, 100-110 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, and LC-CDR3, which comprises an amino acid sequence as shown in any one of SEQ ID NOs: 11-12, 111-126 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0335] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-2, 28-47, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 3-4, 48-64, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 5-6, 65-84, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 7-8, 85-99, an LC-CDR2 comprising the amino acid sequence of SEQ ID NOs: NOs: 9-10, 100-110, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 11-12, 111-126, or a variant of the light chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the LC-CDR sequence. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0336] 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: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-2, 28-47, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 3-4, 48-64, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 5-6, 65-84, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 7-8, 85-99, an LC-CDR2 comprising the amino acid sequence of SEQ ID NOs: 85-99, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NOs: 95-100. NOs: 9-10, 100-110, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 11-12, 111-126, or a variant of the light chain variable domain comprising a substitution of up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acids in the LC-CDR sequence. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0337] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-2, 28-47, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 3-4, 48-64, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 5-6, 65-84; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 7-8, 85-99, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-10, 100-110, and an LC-CDR3 comprising the amino acid sequence of any one of 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 consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0338] 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: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-2, 28-47, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 3-4, 48-64, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 5-6, 65-84; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 7-8, 85-99, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 9-10, 100-110, and an LC-CDR3 comprising the amino acid sequence of any one of 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 consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0339] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0340] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0341] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 100, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 111. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0342] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 86, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 101, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 112. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0343] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 87, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 113. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0344] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0345] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 32, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0346] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 89, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0347] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0348] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 72; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 90, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 116. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0349] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0350] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0351] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 92, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 107, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 118. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0352] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 58, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 93, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 119. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0353] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0354] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 94, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 121. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0355] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:41, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:60, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:79; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0356] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:42, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:120. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0357] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:42, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:120. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0358] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 122. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0359] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 96, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 110, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0360] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 97, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0361] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 98, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0362] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0363] 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) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0364] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 3, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 9, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0365] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0366] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 28, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 48, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 85, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 100, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 111. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0367] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 86, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 101, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 112. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0368] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 87, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 113. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0369] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 68; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0370] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 32, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 69; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0371] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 33, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 52, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 70; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 89, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 115. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0372] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 34, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 71; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0373] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 35, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 54, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 72; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 90, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 116. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0374] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0375] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0376] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 31, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 92, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 107, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 118. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 38, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 58, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 93, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 108, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 119. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 39, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0379] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 40, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 59, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 94, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 121. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO:41, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO:60, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO:79; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO:88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO:103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO:114. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0382] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 42, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 51, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 88, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 120. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 122. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0384] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 44, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 62, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 96, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 110, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0385] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 97, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 104, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 124. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 46, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 53, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 98, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 114. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0387] 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 47, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 64, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 99, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 103, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 125. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of 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: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 43, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 61, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 95, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 109, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0389] 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 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149 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 to the amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149; and a light chain variable domain (V L ), the V Lcomprising the amino acid sequence of any one 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 to the amino acid sequence of any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0390] 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 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149 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 to the amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149; and a light chain variable domain (V L ), the V L The invention also provides an IgG2 antibody comprising an amino acid sequence as set forth in any one 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 to the amino acid sequence as set forth in any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG2 antibody is a human IgG2 antibody. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0391] 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 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149 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 to the amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149; and a light chain variable domain (V L ), the V L The invention also provides an IgG3 antibody comprising an amino acid sequence as set forth in any one 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 to the amino acid sequence as set forth in any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG3 antibody is a human IgG3 antibody. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0392] 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 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149 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 to the amino acid sequence as shown in any one of SEQ ID NOs: 13-17, 127-149; and a light chain variable domain (V L ), the V Lcomprising the amino acid sequence of any one 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 to the amino acid sequence of any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0393] 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 comprising the amino acid sequence shown in any one of SEQ ID NOs: 13-17, 127-149, and a light chain variable domain (V L ), the V L comprising the amino acid sequence of any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of 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 heavy chain variable domain (V H ), the VH comprising the amino acid sequence shown in any one of SEQ ID NOs: 13-17, 127-149, and a light chain variable domain (V L ), the V L comprising the amino acid sequence of any one of SEQ ID NOs: 18-20, 150-171. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0395] 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 , comprising the amino acid sequence of SEQ ID NO: 13 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 13; and V L , which comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0396] 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, comprising the amino acid sequence of SEQ ID NO: 14 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 14; and V L , which comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0397] 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 , comprising the amino acid sequence of SEQ ID NO: 15 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 15; and V L , which comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0398] 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, comprising the amino acid sequence of SEQ ID NO: 16 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 16; and V L , which comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 19. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0399] 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 , comprising the amino acid sequence of SEQ ID NO: 17 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 17; and V L , which comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 20. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0400] 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, comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO: 127; and V L , which comprises the amino acid sequence set forth in SEQ ID NO: 150 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence set forth in SEQ ID NO: 150. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24.

[0401] 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 , comprising the amino acid sequence shown in SEQ ID NO: 128 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 128; and V L , which comprises the amino acid sequence set forth in SEQ ID NO: 151 or a variant thereof, said variant having at least about 80% sequence identity with the amino acid sequence set forth in SEQ ID NO: 151. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 24. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 23. In some embod...

Claims

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

11.

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

19.

3. An isolated anti-Nogo-A antibody, wherein the anti-Nogo-A antibody comprises: Heavy chain variable domain (V H ), the V H Include: a heavy chain complementarity determining region (HC-CDR) 1 comprising the amino acid sequence set forth in SEQ ID NO: 28; HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 48; and HC-CDR3 comprising the amino acid sequence shown in SEQ ID NO: 65; and Light chain variable domain (V L ), the V L Include: a light chain complementarity determining region (LC-CDR) 1 comprising the amino acid sequence set forth in SEQ ID NO: 85; LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 100; and LC-CDR3 comprises the amino acid sequence shown in SEQ ID NO:

111.

4. The isolated anti-Nogo-A antibody according to claim 3, comprising: (i)V H , comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 127; and V L , comprising the amino acid sequence of SEQ ID NO: 150 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 150; (ii)V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , comprising the amino acid sequence of SEQ ID NO: 151 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 151; or (iii)V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , comprising the amino acid sequence of SEQ ID NO: 150 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:

150.

5. An isolated anti-Nogo-A antibody comprising: (i)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 4, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 6; and V L , the V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12; (ii)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 29, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 49, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 66; and V L , the V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 86, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 101, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 112; (iii)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 30, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 50, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 67; and V L , the V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 87, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 102, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 113; (iv)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 36, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 55, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 73; and V L , the V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; (v)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 37, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 56, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74; and V L , the V L comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 91, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 106, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 117; or (vi)V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 45, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 63, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:97, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:104, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:

124.

6. The isolated anti-Nogo-A antibody according to claim 5, comprising: (i)V H , comprising the amino acid sequence of SEQ ID NO: 17 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 17; and V L , comprising the amino acid sequence of SEQ ID NO: 20 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 20; (ii)V H , comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 129; and V L , comprising the amino acid sequence of SEQ ID NO: 152 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 152; (iii)V H , comprising the amino acid sequence of SEQ ID NO: 130 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 130; and V L , comprising the amino acid sequence of SEQ ID NO: 153 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 153; (iv)V H , comprising the amino acid sequence of SEQ ID NO: 136 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 136; and V L , comprising the amino acid sequence of SEQ ID NO: 159 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 159; (v)V H , comprising the amino acid sequence of SEQ ID NO: 137 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 137; and V L , comprising the amino acid sequence of SEQ ID NO: 159 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 159; or (vi)V H , comprising the amino acid sequence of SEQ ID NO: 146 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 146; and V L , comprising the amino acid sequence of SEQ ID NO: 168 or a variant thereof, wherein the variant has at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:

168.

7. The isolated anti-Nogo-A antibody according to any one of claims 1 to 6, wherein the anti-Nogo-A antibody binds to human Nogo-A with a Kd value of about 0.1 pM to about 10 nM.

8. The isolated anti-Nogo-A antibody according to any one of claims 1 to 7, wherein the anti-Nogo-A antibody comprises an Fc fragment.

9. The isolated anti-Nogo-A antibody according to claim 8, wherein the anti-Nogo-A antibody is a full-length IgA, IgD, IgE, IgG or IgM antibody.

10. The isolated anti-Nogo-A antibody according to claim 9, wherein the anti-Nogo-A antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.

11. The isolated anti-Nogo-A antibody according to any one of claims 1 to 10, wherein the anti-Nogo-A antibody is a chimeric, human or humanized antibody.

12. The isolated anti-Nogo-A antibody according to any one of claims 1 to 7, wherein the anti-Nogo-A antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody and linear antibody.

13. An isolated nucleic acid molecule encoding the anti-Nogo-A antibody of any one of claims 1-12.

14. A vector comprising the nucleic acid molecule of claim 13.

15. An isolated host cell comprising the anti-Nogo-A antibody of any one of claims 1 to 12, the nucleic acid molecule of claim 13 or the vector of claim 14.

16. A method for preparing an anti-Nogo-A antibody, comprising: a) culturing the host cell according to claim 15 under conditions that effectively express the anti-Nogo-A antibody; and b) Obtaining the expressed anti-Nogo-A antibody from the host cells.

17. A pharmaceutical composition comprising the anti-Nogo-A antibody according to any one of claims 1 to 12, the nucleic acid molecule according to claim 13, the vector according to claim 14, the isolated host cell according to claim 15 or the antibody produced by the method according to claim 16, and a pharmaceutically acceptable carrier.

18. Use of the antibody of any one of claims 1 to 12, the nucleic acid molecule of claim 13, the vector of claim 14, the host cell of claim 15, the antibody produced by the method of claim 16, or the pharmaceutical composition of claim 17 in the preparation of a medicament for treating a disease or condition in an individual in need thereof.

19. The use according to claim 18, wherein the disease or disorder is a disease and / or disorder caused by dysregulation of the Nogo-A signaling pathway, such as a central nervous system and / or peripheral nervous system disease or trauma.

20. The use according to claim 19, wherein the disease or condition is selected from neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Lewy body-like disease, other common dementias, post-traumatic diseases of the cranium, brain or spinal cord, stroke, demyelinating diseases such as multiple sclerosis, monophasic demyelination, encephalomyelitis, multifocal leukoencephalitis, panencephalitis, Marchiafava-Bignami disease, pontine myelmolysis, adrenoleukodystrophy, Pelitzowitz-Merzbacher disease, spongiform encephalitis, myeloma, leukoencephalitis ... Encephalopathy, Alexander disease, spongiform degeneration of the white matter, metachromatic leukodystrophy and Krabbe's disease, degenerative visual diseases such as general ischemic retinopathy, anterior ischemic optic neuropathy, optic neuritis, age-related macular degeneration, diabetic retinopathy, cystic macular edema (CME), retinitis pigmentosa, Šgurdsson disease, Best's vitelliform retinal degeneration, Leber's congenital amaurosis and other hereditary retinal degenerations, pathological myopia, retinopathy of prematurity and Leber's hereditary optic neuropathy, psychiatric diseases such as schizophrenia, depression.

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