CN114409784B

CN114409784B - OMgP antibodies and their use in spinal cord injury

Info

Publication number: CN114409784B
Application number: CN202210101578.0A
Authority: CN
Inventors: 牟春琳
Original assignee: Tianjin Changhe Biological Technology Co ltd
Current assignee: Tianjin Changhe Biological Technology Co ltd
Priority date: 2022-01-27
Filing date: 2022-01-27
Publication date: 2023-05-09
Anticipated expiration: 2042-01-27
Also published as: CN114409784A

Abstract

The invention relates to the biomedical field, in particular to an OMgP antibody and application thereof in spinal cord injury. The OMgP antibody prepared by the invention has high affinity and good specificity, and particularly, the antibody has the important advantages of activity and physical stability of binding and neutralizing OMgP, so the antibody can be preferably used as an antibody drug, and has excellent application prospect in the treatment of spinal cord injury.

Description

OMgP antibodies and their use in spinal cord injury

Technical Field

The invention relates to the biomedical field, in particular to an OMgP antibody and application thereof in spinal cord injury.

Background

The term "spinal cord injury" (Spinal Cord Injury) refers to damage to the spinal cord caused by trauma (e.g., a crash), disease, or degeneration (e.g., cancer). There is currently no reliable estimate of global prevalence, but most are caused by trauma, although the proportion of non-traumatic spinal cord injuries is on the rise. Symptoms of spinal cord injury depend on the severity of the injury and the location of the injured spinal cord. Symptoms may include a partial or complete loss of sensory or motor control function of the arm, leg and/or body. The most severe spinal cord injury affects the body system that regulates urinary control, respiration, heart rate, and blood pressure. Most spinal cord injured individuals experience chronic pain and spinal cord injury is at risk of developing secondary diseases such as deep vein thrombosis, urinary tract infections, muscle spasms, osteoporosis, decubitus ulcers, chronic pain and respiratory complications, which can lead to debilitation and even life threatening. Emergency care, rehabilitation services and continuous health maintenance are critical to the prevention and management of these diseases. The consequences are lifelong and devastating, not only causing great pain to the patient, but also placing a heavy burden on the home and society.

Currently, the adverse factors affecting regeneration after spinal cord injury are believed to be mainly myelin-associated inhibitory molecules and glial scars. Myelin associated glycoprotein-associated myelin glycoprotein (OMgP) is one of myelin associated inhibitory molecules, and the prior art shows that OMgP is a major inhibitor of spinal cord regeneration, and it has been reported in the prior art that siRNA and the like interfere with expression of OMgP, but siRNA is usually delivered by techniques such as exosomes, viruses, lipid nanoparticles, and polymer nanoparticles, and RNA molecules are unstable and are easily degraded.

In view of this, the present invention has been made.

Disclosure of Invention

The invention relates to an OMgP antibody or antigen binding fragment thereof, which comprises heavy chain complementarity determining regions CDR-VH1, CDR-VH2 and CDR-VH3 with amino acid sequences shown in SEQ ID NO. 1-3, and light chain complementarity determining regions CDR-VL1, CDR-VL2 and CDR-VL3 with amino acid sequences shown in SEQ ID NO. 4-6.

In the present invention, the term "antibody" is a protein that binds to a specific antigen, which refers broadly to all proteins and protein fragments, particularly full length antibodies, that contain CDR regions. The term "full length antibody" includes polyclonal antibodies as well as monoclonal antibodies, and the term "antigen binding fragment" is a substance comprising a portion or all of the CDRs of an antibody that lacks at least some of the amino acids present in the full-length chain but is still capable of specifically binding to an antigen. Such fragments are biologically active in that they bind to a target antigen and can compete with other antigen binding molecules (including intact antibodies) for binding to a given epitope. In some embodiments, the antibody functional fragment has the effect of specifically recognizing and binding OMgP. In one aspect, such fragments will comprise a single heavy chain and a single light chain, or portions thereof. The fragments may be produced by recombinant nucleic acid techniques, or may be produced by enzymatic or chemical cleavage of antigen binding molecules, including intact antibodies.

The term "complementarity determining regions" or "CDRs" refers to the highly variable regions of the heavy and light chains of immunoglobulins, as defined by Kabat et al (Kabat et al Sequences of proteins of immunological interest,5th Ed"US Department ofHealth and Human Services,NIH,1991, and later versions) are employed in the present invention. There are three heavy chain CDRs (HCDR) and three light chain CDRs (LCDR). Here, the terms "CDR" and "CDRs" are used to refer to regions comprising one or more or even all of the major amino acid residues that contribute to the binding affinity of an antibody to its recognized antigen or epitope, depending on the circumstances.

Alternatively, an OMgP antibody, or antigen binding fragment thereof, as described above, comprising a heavy chain variable region HCVR as set forth in SEQ ID NO. 7 and a light chain variable region LCVR as set forth in SEQ ID NO. 8.

Variants of antibodies or antigen-binding fragments thereof are also within the scope of the invention, the antibodies or antigen-binding fragments thereof of the invention comprise heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3, and HCVR and LCVR, wherein the sequences of the variants of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, and HCVR and LCVR, respectively, comprise a mutation of up to 3 amino acids (e.g., substitution, deletion or addition of 1, 2 or 3 amino acids, or any combination thereof) as compared to any of the sequences set forth in SEQ ID NOs 1-8; preferably a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity.

The term "antigen binding fragment" includes antigen compound binding fragments of such antibodies, including Fab, F (ab ') 2, fd, fv, scFv, the smallest recognition unit of an antibody, as well as single chain derivatives of such antibodies and fragments, e.g., scFv-Fc, and the like, preferably F (ab') ₂ 、Fab、scFv。

Preferably, an OMgP antibody, or antigen binding fragment thereof, as described above, has a constant region.

Further preferred, the heavy chain constant region sequence is selected from the constant region sequences of any one of IgG, igA, igM, igE, igD; wherein the IgG may be further divided into subclasses, e.g. selected from the group consisting of IgG1, igG2, igG3, igG4.

Further preferred, the light chain constant region is a kappa or lambda chain;

further preferably, the constant region is of a species source selected from bovine, equine, porcine, ovine, murine, canine, feline, rabbit, camel, donkey, deer, mink, chicken, duck, goose, or human.

Alternatively, an antibody or antigen binding fragment thereof as described above is a mouse antibody, a human-mouse chimeric antibody or a humanized antibody.

According to a further aspect of the invention, there is also provided an isolated nucleic acid encoding an OMgP antibody or antigen binding fragment thereof as defined above.

The invention also relates to a vector comprising a nucleic acid as described above. The term "vector" refers to a nucleic acid vehicle into which a polynucleotide may be inserted. When a vector enables expression of a protein encoded by an inserted polynucleotide, the vector is referred to as an expression vector. The vector may be introduced into a host cell by transformation, transduction or transfection such that the genetic material elements carried thereby are expressed in the host cell. Vectors are well known to those skilled in the art and include, but are not limited to: a plasmid; phagemid; a cosmid; artificial chromosomes, such as Yeast Artificial Chromosome (YAC), bacterial Artificial Chromosome (BAC), or P1-derived artificial chromosome (PAC); phages such as lambda phage or M13 phage, animal viruses, etc. Animal viruses that may be used as vectors include, but are not limited to, retrovirus (including lentivirus), adenovirus, adeno-associated virus, herpes virus (e.g., herpes simplex virus), poxvirus, baculovirus, papilloma virus, papilloma vacuolation virus (e.g., SV 40). In some embodiments, the vectors of the invention comprise regulatory elements commonly used in genetic engineering, such as enhancers, promoters, internal Ribosome Entry Sites (IRES) and other expression control elements (e.g., transcription termination signals, or polyadenylation signals, and poly U sequences, etc.).

The invention also relates to a host cell comprising a nucleic acid as described above or a vector as described above. The term "host cell" refers to a cell that can be used to introduce a vector, and includes, but is not limited to, a prokaryotic cell such as E.coli or Bacillus subtilis, a fungal cell such as a yeast cell or Aspergillus, an insect cell such as S2 Drosophila cell or Sf9, or an animal cell such as a fibroblast, CHO cell, COS cell, NSO cell, heLa cell, BHK cell, HEK 293 cell or human cell. The host cell is preferably a eukaryotic cell, more preferably a mammalian cell.

The invention also relates to a pharmaceutical composition comprising an OMgP antibody or antigen-binding fragment thereof as described above, and one or more of a pharmaceutically acceptable excipient, diluent or carrier.

The term "pharmaceutically acceptable excipient, diluent or carrier" refers to an excipient, diluent or carrier that is pharmacologically and/or physiologically compatible with the subject and active ingredient, and is well known in the art, including but not limited to: pH adjusters, surfactants, adjuvants, ionic strength enhancers. For example, pH modifiers include, but are not limited to, phosphate buffers; surfactants include, but are not limited to, cationic, anionic or nonionic surfactants, such as Tween-80; ionic strength enhancers include, but are not limited to, sodium chloride.

The invention also relates to the use of an OMgP antibody or antigen binding fragment thereof as described above in the manufacture of a medicament for the treatment of spinal cord injury.

The beneficial effects are that:

the OMgP antibody prepared by the invention has high affinity and good specificity, and particularly, the antibody has the important advantages of activity and physical stability of binding and neutralizing OMgP, so the antibody can be preferably used as an antibody drug, and has excellent application prospect in the treatment of spinal cord injury.

Detailed Description

Reference now will be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment can be used on another embodiment to yield still a further embodiment.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.

Embodiments of the present invention will be described in detail below with reference to examples.

Example 1 preparation of antibodies

1. Protein design and expression

The antigen and protein for detection of the present invention were obtained by designing the amino acid sequence of the antigen and protein for detection of the present invention using Oligldrocyte-associated myelin glycoprotein (human OMgP, uniprot: Q16653) as a template for OMgp of the present invention, fusing Flag-his tag on the basis of OMgP protein, cloning onto pTT5 vector (Biovector, cat #: 102762), and transiently expressing or stably expressing and purifying CHO-S in 293 cells.

2. Protein purification

The cell expression liquid is centrifuged at a high speed, the supernatant is collected, and the precipitate is discarded. HisTrap FF pre-packed columns were equilibrated with Phosphate Buffer (PBS) in 5-10 column volumes. Cell expression supernatants were loaded at a rate of 2 ml/min. Washing the pre-packed column with PBS until mAu reading is performed to obtain a baseline, eluting the target protein with 20mM, 50mM and 250mM imidazole with pH7.4 in sequence, collecting the target protein, transferring 300mM imidazole-eluted target protein solution into a concentration tube, centrifuging, changing the solution, and replacing the target protein into a PBS solution for storage for later experiments.

3. Antigen immunization and monoclonal preparation

Conjugates of human OMgP and mouse antibody Fc fragment (Fragment crystallizable) were intraperitoneally injected into BALB/c mice once a week, 100 μg/200 μl/each time, 3 weeks after immunization, mouse tail blood was taken weekly and the expression of OMgP antibodies in serum was detected; selecting mice with high OMgP antibody expression in serum (dot blot detection), and fusing spleen cells with SP2/0 myeloma cells to form a fusion seed.

Cell fusion method:

cell fusion was carried out using 50% peg with molecular weight 1450 as a fusion agent, and the cell fusion was carried out according to a conventional method, and the procedure was as follows:

taking 1×10 ⁷ The SP2/0 myeloma cells were mixed with the immunoregulatory cells, resuspended in basal medium, and the cells were washed three times for 5min at 2000 r/min. Taking out sterilized water absorbing paper in an ultra-clean workbench, and after the supernatant of a 50mL centrifuge tube filled with mixed cells of myeloma cells and immune cells is completely poured out, reversely buckling the supernatant on the water absorbing paper to control water drops. With small aluminium pots2/3 volume of water is filled, and the water is heated to 37 ℃ on an electric furnace and then is put into an ultra-clean workbench; from CO ₂ Taking out 50% PEG incubated to 37 ℃ in an incubator, sucking 0.8mL by a 1mL suction tube, holding a 50mL centrifuge tube filled with mixed cells, placing the centrifuge tube in a small aluminum pot in a 37 ℃ water bath, slowly adding PEG to the mixed cells while gently stirring for 2min, inserting the centrifuge tube into a centrifuge tube rack, removing the small aluminum pot, and removing CO from the centrifuge tube ₂ Taking out 50mL of basic culture solution incubated to 37 ℃, slowly adding 10mL of basic culture solution onto the fused cells by using a suction pipe, adding light stirring while stirring to disperse cell aggregates, adding 1mL, then adding 2mL, then adding 3mL, finally adding the rest 4mL, adding the first 10mL, then adding the rest 40mL along the pipe wall, screwing a cover after adding, repeatedly reversing for several times, and uniformly mixing the cells. 1500r/min, centrifugation for 5min, discarding the supernatant and resuspension of the fused cells with 72mL of complete medium with feeder cells resuspended. And (3) injection: the action is light, the cells are gently stirred by a suction tube, and the cells are not blown. Dripping the resuspended cells into 96-well cell culture plate, 2 drops/well, and placing CO ₂ Culturing in an incubator. Small colonies were observed on day 4 after fusion; 1 drop/well of complete broth was added on day 7; on about day 10, colonies grow to 1/4 of the size of the bottom of the wells, and the culture solution turns yellow, so that antibody detection can be performed.

Screening and cloning of hybridoma-positive clones:

10 th to 14 th days after fusion, the culture plate is observed under an inverted microscope, small points are marked on the upper side of the culture plate cover with the colony occurrence holes by using a marker pen, and the positions of the colonies are marked so as to facilitate sampling during detection and checking and seating of the original holes.

Selecting a fusion gene expressing OMgP antibody in culture supernatant for monoclonal; and (3) selecting a monoclonal hybridoma cell strain expressing the OMgP antibody for expansion culture, and collecting a cell culture solution after 7-10 days of culture and purifying to obtain the OMgP antibody.

Example 2 antibody assay

1) Determination of antibody Activity

1. The probe with the surface coupled Protein A Protein is soaked in 250 mu L buffer K (PBS+0.002% Tween 20+0.02% BSA) for 10 minutes;

2. the buffer K for the antibody is configured as a working solution with the concentration of 5 mug/mL;

3. preparing four working solutions with concentrations of 10 mug/mL, 5 mug/mL, 2.5 mug/mL and 0 mug/mL by using buffer K for recombinant human OMgP protein;

4. according to the Gator non-marking analyzer (Star child medical technology, CAT#: gator) indicated that reagent is added, the affinity data are shown in table 1, and the 9 clones with better primary screening effect are detected. The detection result shows that the OMgP E4-3 clone has the highest affinity level with human OMgP protein, wherein, the K of 7 antibodies in 9 antibodies _D In the low nanomolar range (10 ^-9 ) K belonging to high affinity antibody, 1 strain antibody _D At 10 ^-11 Within the scope of clone No. 6K _D In the picomolar range (10) ^-12 ) Belonging to antibodies with very high affinity.

TABLE 1

Clone numbering	koff(1/s)	kon(1/Ms)	K _D (M)
				OMgP A2-1	4.35E-04	1.70E+05	2.56E-09
OMgP B2-8	2.71E-04	2.45E+05	1.11E-09
				OMgP C3-1	9.13E-04	4.11E+05	2.22E-09
OMgP C5-1	4.61E-04	6.36E+04	7.25E-09
				OMgP B7-2	1.80E-04	1.56E+05	1.15E-09
OMgP E4-3	4.60E-06	6.11E+05	7.53E-12
				OMgP F4-1	2.36E-04	7.18E+04	3.29E-09
OMgP F10-1	3.31E-04	7.19E+04	4.60E-09
				OMgP H6-3	5.24E-05	1.57E+06	3.34E-11

2) Physical stability detection of antibodies

The thermostability of OMgP E4-3 and OMgP H6-3 antibodies was examined by DSC (Differential scanning calorimetry ). Differential thermal scanners (DSC) induce changes in macromolecules by increasing or decreasing temperature, thereby measuring thermodynamic changes in molecular interactions, and are the preferred technique for characterizing the thermal stability of molecules.

Both antibodies were diluted to the same concentration and the assays were performed according to the instructions of MicroCal VP-capery DSC (Malvern). Before detection, each sample and blank buffer are degassed by a vacuum degasser for 1 min-2 min. 500. Mu.l of sample or blank buffer (300. Mu.l of instrument loading) was added to each well of the sample plate. The final two pairs of well plates were filled with 14% Decon 90 and ddH, respectively ₂ O, in order to prepare for cleaning, after the sample plate is loaded, the plastic soft cover plate is sleeved. The scanning temperature starts from 25 ℃ to 100 ℃ and the scanning speed is 60 ℃/h. The specific results are shown in Table 2.

TABLE 2

Antibodies are relatively stable proteins, and have a Tm of substantially about 70 degrees. However, the better the thermal stability of the antibody protein used as a drug, the less susceptible the degradation during transportation/storage. From the experimental results, OMgP E4-3 showed better thermal stability than OMgP H6-3.

The purity of the sample is monitored by SEC-HPLC, the periodic stability under a certain concentration condition is examined, the concentration of the sample is controlled to be about 1mg/ml, and the stability condition of the antibody in a PBS system under repeated freezing and thawing for 3 times (the freezing temperature is-70 ℃ each time and the room temperature is naturally thawed) is detected. Antibody purity was checked using a Xbridge protein BEH SEC 200A (Waters) HPLC column. The results are shown in Table 3, and in PBS, the antibody OMgP E4-3 showed better stability than OMgP H6-3.

TABLE 3 Table 3

OMgP E4-3(△％)	OMgP H6-3(△％)
		2.7	4.9

Remarks: delta% refers to the rate of change in HPLC purity decrease

Sequencing of OMgP E4-3 antibody the heavy chain variable region amino acid sequence VH is shown in SEQ ID NO. 7, and the light chain variable region amino acid sequence VL is shown in SEQ ID NO. 8. The antibody type is IgG.

Heavy Chain variable region:(SEQ ID NO:7)

QVQLQKSDAEFVKPGASVKISCKASGYTASAAYWVKQNPEQQLEKIGYWSPGSSDLKSSVEFFKGKATLTADKSSSTEYVQLASLVSEDSAVYFCAMSINMAYWGWGQGTQVQQVSSQQ

Light Chain variable region:(SEQ ID NO:8)

SIVMTQTPKFLLVSAGDRVTITCKASQVQSFCNTWYKQKSKPGESPKDLVYVYSSRDSGVPDRFIGSGTAGSFTFTLTISSLQVEDLADYFCQQHASSPYMSTMAGGKLELK

Example 3 Tail intravenous antibody accelerates recovery from spinal cord injury

The experimental method is as follows:

1. experimental animal

The experimental animals were SD male rats of 250 g-280 g purchased from Beijing Vitre Lihua experimental animal technologies Co. The animals were kept in a constant temperature environment at 23deg.C with a humidity of 40%,12/12hr circadian rhythm. The rat diet and water were supplied in sufficient quantity.

2. And (6) establishing a rat spinal cord hit injury model.

Reference is made to the method of Wamil et al [ Wamil et al Proc Natl Acad Sci USA,1998;95 (22): 13188-13193) is modeled according to the principle of falling body injury. The device comprises a striking rod, a peripheral sleeve, a hammer, an external fixing frame and the like. The diameter of the head end of the striking rod is 2.3mm, the height is 10mm, the weight of the striking hammer is 10g, the falling height is 1.25cm, and the impact force of falling injury is 10 multiplied by 1.25 g.cm. Animals were weighed at room temperature at 23℃and anesthetized by intraperitoneal injection with 5% chloral hydrate (0.75 ml/100 g) and fixed on rat holders. The skin and subcutaneous tissue of the spinal cord chest and back are cut along the midline to be about 4cm long, the spinous process of the T11 vertebral body is positioned, muscles at two sides of the T11, 10 and 9 vertebral bodies are passively separated, and the spreader is spread and fixed to expose the three vertebral bodies for laminectomy. The head end of the striking rod is arranged in the T10 section spinal cord, the striking outer sleeve is fixed, the striking hammer freely falls down along the peripheral sleeve from the height of 1.25cm to strike the striking rod, the T10 section spinal cord contusion is caused, and the body can be seen to flutter forwards in operation, the tail is thrown, and the apnea indicates that the molding is successful. Gelatin sponge is used for stopping bleeding, muscle, subcutaneous tissue and skin are sewn layer by layer, water is freely fed after operation, and the gelatin sponge is fed in separate cages. The bladder urinates for 4-5 times daily, lasting for 1-2 w until the urination reflex is recovered.

3. Experimental grouping and antibody administration strategy

According to the reference document ("expression of OMgP protein in acute injury of rat and meaning thereof", yuan Puwei et al, chinese J Trad Med Traum & Orthop, jun 2008, vol16, no. 6), the expression level of OMgP protein is increased 1h after acute spinal cord injury, and the expression level reaches a peak at 1 week. The tail vein was selected for antibody injection three times after successful spinal cord injury model establishment for 24h, 3d and 7 d. The experiment was divided into groups of 8 animals each.

Control: blank control group, PBS+IgG was injected, antibody concentration 10. Mu.g/g;

group1, tail vein injection PBS+OMgPE4-3 antibody, antibody concentration 5 μg/g (by rat body weight);

group2, tail vein injection PBS+OMgPE4-3 antibody, antibody concentration 10 μg/g;

group3, tail vein injection PBS+OMgPE4-3 antibody, antibody concentration 15 μg/g;

4. efficacy assessment

4.1BBB scoring was performed by double blind experiments, assessing experimental rat hind limb function, including joint movement, walking ability, coordination and limb stability, respectively. BBB scoring was performed for each group at 30d after spinal cord injury.

Statistical analysis data processing employs SPSS15.0 software, results to

And (3) representing. BBB scoring and cell counting were performed using paired t-test or one-way analysis of variance (ANOVA). P is p<0.05 is statistically significant.

The rat hind limb BBB scores are referenced in table 4.

Table 4 BBB athletic functionality scoring table

The scoring of each group before operation is 21 points, and the scoring after injury is 0 point. After 30d rest, the Control group obtains preliminary recovery, and the scores of the other groups relative to the Control group are improved remarkably.

TABLE 5

Note that: * p < 0.05, vs Control.

From the results, the OMgP antibody prepared by the invention can effectively inhibit the activity of OMgP protein under the concentration of 10 mug/g or above, thereby accelerating the recovery of spinal cord injury and having good application prospect.

The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.

The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.

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Claims

OMgP antibody or antigen binding fragment thereof, characterized in that it comprises heavy chain complementarity determining regions CDR-VH1, CDR-VH2, CDR-VH3 with amino acid sequences shown in SEQ ID NO 1-3 in sequence, and light chain complementarity determining regions CDR-VL1, CDR-VL2, CDR-VL3 with amino acid sequences shown in SEQ ID NO 4-6 in sequence.
2. The OMgP antibody or antigen-binding fragment thereof according to claim 1, comprising a heavy chain variable region HCVR as set forth in SEQ ID No. 7 and a light chain variable region LCVR as set forth in SEQ ID No. 8.
3. The OMgP antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antigen-binding fragment is F (ab') ₂ Fab, scFv, and bispecific antibody.
4. The OMgP antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody has a constant region and the heavy chain constant region sequence is selected from the constant region sequences of any one of IgG, igA, igM, igE, igD; the light chain constant region is a kappa or lambda chain;

the constant region is derived from a species selected from the group consisting of bovine, equine, porcine, ovine, murine, canine, feline, rabbit, donkey, deer, mink, chicken, duck, goose, and human.
5. The antibody or antigen-binding fragment thereof according to claim 4, which is a mouse antibody, a human-mouse chimeric antibody or a humanized antibody.
6. An isolated nucleic acid encoding the omp antibody or antigen-binding fragment thereof of any one of claims 1-5.
7. A vector comprising the nucleic acid of claim 6.
8. A host cell comprising the nucleic acid of claim 6 or the vector of claim 7.
9. A pharmaceutical composition comprising an OMgP antibody or antigen-binding fragment thereof according to any one of claims 1 to 5 and one or more of a pharmaceutically acceptable excipient, diluent or carrier.
10. Use of an OMgP antibody or antigen-binding fragment thereof according to any one of claims 1 to 5 in the manufacture of a medicament for the treatment of spinal cord injury.