FORM 2 THE PATENTS ACT, 1970 (39 OF 1970) AND THE PATENT RULES, 2003 PROVISIONAL SPECIFICATION (See section 10; rule 13) Title of the Invention: 93 "Anti-RhD Monoclonal Antibodies Applicant(s): (a) Name BHARAT SERUMS AND VACCINES LTD. (b) Nationality An Indian company Incorporated under the Companies Act 195S, (c) Address- 16th and 17th Floor, Hoechst House, Nariman Point Mumbai - 400 021. Maharashtra, India. The present invention relates to the production and use of anti-Rhesus D mononclonal antibodies and antigen binding fragments thereof. Background and prior art 5 Rhesus D antigen (also referred to in the art as RhD antigen, Rhesus factor, and/or Rh factor) is an antigen which may be present on the surface of human red blood cells. Those individuals whose red blood cells have this antigen are usually referred to as "RhD-positive", while those individuals whose 10 red blood cells do not have this antigen are referred to as "RhD-negative". A person who is RhD-negative and has never been exposed to the RhD antigen will not produce anti-RhD antibodies (antibdoies against the RhD antigen). However, transfer of RhD-positive blood to a RhD-negative individual 15 will lead to sensitisation (immunization) of the RhD-negative individual against the RhD antigen. This can lead to a number of complications. In particular, where a RhD-negative woman gives birth to a RhD-positive infant there is a risk of small amounts of the infant's blood entering the maternal circulation, causing the the mother to produce anti-RhD antibodies. Whilst this will not normally harm 20 the first baby, should the now immunized mother fall pregnant with another RhD positive child then maternal anti-RhD antibodies may cross the placenta and attack the infant's blood cells, leading to a condition known as haemolytic disease of the newborn (HDN). 25 Anti-RhD antibodies are therefore routinely administered to RhD- negative patients where there is a risk of exposure to RhD-positive blood, in order to prevent the patient from becoming immunized against the RhD-positive blood. For example, a RhD-negative patient may be given anti-RhD antibodies: prior to and/or shortly after giving birth to or having an abortion of an RhD-positve 30 baby; after any incident during pregnancy which may have lead to bleeding across the placenta; as a routine preventative measure during pregnancy; or prior to or soon after any transfusion of blood components containing RhD-positive red blood cells. Traditionally, the anti-RhD antibodies used have been polyclonal antibodies obtained from the blood plasma of RhD negative volunteers who have been repeatedly immunized against RhD-positive red blood cells. However, the use of polyclonal antibodies has a number of recognised drawbacks, not least of 5 which are the continuing need for a number of volunteer donors sufficient to meet the demand for antibody, and the risk of contamination of the antibody preparation with any viruses or other pathogens that may be present in the donor's blood. 10 Whereas polyclonal antibodies constitute antibodies secreted by a number of different plasma cells, and thus constitute a mixture of immunoglobulin molecules secreted against a specific antigen and potentially recognising a variety of epitopes, monoclonal antibodies are produced from cells that are all clones of a single parent cell, and thus constitute a homogeneous population of 15 antibodies, as is well known in the art. The cell lines from which monoclonal antibodies are produced are developed and cultured in-vitro, and this means monoclonal antibodies have the potential to be produced as and when required both in large amounts and at high levels of purity. Accordingly, monoclonal anti-RhD antibodies have a number of potential advantages over the polyclonal anti- 20 RhD antibody preparations that have traditionally been used. A number of techniques for producing human monoclonal antibodies in general, and human monoclonal anti-RhD antibodies in particular, have been described. For example, EP-A2-0251440 discloses an anti-RhD monoclonal 25 antibody producing heterohybridoma formed by fusion of non-lg secreting mouse myfenoma cells with an anti-RhD Ig producing population of Epstein Barr virus (EBV) transformed human lymphocytes. US 5,665,356 describes the production of human monoclonal anti-RhD 30 antibodies having certain defined characteristics, produced by culturing selected EBV-transformed human B-lymphocytes. US 6,312,690 describes the production anti-RhD monoclonal antibodies by recombinant techniques. An EBV immortalized human cell line producing an anti-Rhesus D monoclonal antibody called D7C2 was selected. The sequences encoding the variable regions of the heavy (H) and light (L) chains of D7C2 were cloned, sequenced, and inserted into a recombinant baculovirus expression vector under the control of a strong baculovirus promoter. Insect ceils 5 transfected with the recombinant baculovirus were cultured, and the recombinant D7C2 monoclonal antibody recovered from the cell supernatant. US-A1-2003/0175969 describes a method for preparing a anti-RhD monoclonal antibodies capable of activating effector cells expressing FcyRIII, 10 comprising: a) purifying monoclonal antibodies obtained from cell lines selected from human B lymphocyte heterohybridomas, or recombinant animal or human cell lines (such as CHO-K, CHO-LedO, CHO Lec-1, CHO Pro-5, CHO dhfr-, Wii-2, Jurkat, Vero, Molt-4, COS-7, HEK293, YB2/0, BHK, K6H6, NSO, SP2/0-Ag 14 and P3X63Ag8.653 cells); b) adding each antibody obtained in step a) to a 15 different reaction mixture comprising RhD-positive red blood cells, effector cells comprising cells expressing FcyRIII, polyvalent IgGs; and c) determining the percentage lysis of the target cells and selecting the monoclonal antibodies which activate the effector cells causing significant lysis of the RhD-positive red blood cells. 20 US 6,475,787 discloses a method for preparing monoclonal antibodies, in which a suitable eukaryotic host cell is transformed with a DNA sequence encoding an antibody heavy chain and a DNA sequence encoding an antibody light chain, the two sequences being (inked to different amplifiable marker genes 25 so as to allow differential amplification of the heavy and light chain DNAs in order to optimize the relative gene copy numbers of the heavy and light chain DNAs. In a preferred embodiment the host cell is a Chinese Hamster Ovary (CHO) cell which is DHFR deficient (i.e. incapable of producing dihydrofolate reductase), one of the amplifiable marker genes is an adenosine deaminase (ADA) gene, 30 and the other is a DHFR gene. Amplification of the DNA encoding one antibody chain and linked in the ADA gene can then be achieved by treating the recombinant cells with increasing concentrations of 2'-deoxycoformycin, whilst amplification of the DNA encoding the other antibody chain and linked in the DHFR gene is achieved by treating the ceff with increasing concentrations of methotrexate (MTX). Nevertheless, there remains a need for further anti-RhD monoclonal 5 antibodies and methods for the production thereof. Description of the Invention According to a first aspect of the present invention there is provided an 10 isolated anti-RhD monoclonal antibody comprising: a) a heavy chain variable region having first, second and third CDRs (complementarity determining regions) which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 2, and a light chain variable region having first, second and third CDRs which are identical 15 or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 4; or b) a heavy chain variable region having first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 6, and a light chain variable region having first, 20 second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 8; or c) a heavy chain variable region having first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 10, and a light chain variable region having first, 25 second and third CDRs which are identical or substantially identical to the respective first, second, and third CORs of SEQ ID NO; 12. As used herein, the term "anti-RhD antibody" refers to both whole 30 antibodies and to fragments thereof that have binding specificity for RhD antigen. The binding affinity/specificity of an antibody can be measured by a various assays, as will be known to and can be routinely implemented by one of ordinary skill in the art. For example, antibodies recognising and specifically binding to RhD antigen can be determined using one or more standard techniques as known to one of ordinary skill in the art, such as but not limited to: EIA / ELISA techniques, such as competitive EIA (enzyme linked-immunoassay); flow cytometry; and/or ADCC (antibody-dependant cellular toxicity) assays. Exemplary competitive EIA, flow cytometry, and ADCC techniques are described 5 in further detail in the Examples that follow. As is well known in the art, whole antibodies are typically formed of one or two heavy and one or two light chains. The heavy and light chains each comprise a variable region and a constant region. The variable regions (also 10 referred to as the variable domains) dictate the antibody's antigen binding specificity. Each variable domain is composed of complementarity determining regions (CDRs, of which there are typically three, designated CDR1, CDR2 and CDR3) interspersed with more conserved regions known as framework regions. On folding of the antibody to adopt the correct quaternary structure, the CDRs of 15 a heavy and light chain together form the antigen binding site. The constant region of the heavy chain is composed of three or more constant domains and is dependent on the class (eg. IgA, IgD, IgE, IgG, or IgM) and isotype (eg. lgA1, lgA2, lgG1, lgG2, lgG3, lgG4) of the antibody. It is identical in all antibodies of the same class and isotype, but differs in antibodies of different isotypes. The 20 light chain constant region is composed of a single constant domain of which is of one of two isotypes, kappa or lambda, and is likewise identical in all antibodies of the same isotype. The constant regions of the antibodies typically mediate binding of the antibody to host tissues or factors. 25 Antibody fragments according to the present invention typically include at least the CDRs and sufficient of the framework regions to specifically bind the antigen. Exemplary types of fragment include, but are not limited to, a Fab' fragment (consisting of the variable domain and a constant domain of both the light and heavy chains), a F(ab')2 fragment (two Fab' fragments linked by a 30 disulfide bridge at the hinge region), a Fv fragment (consisting of the variable domains only of the light and heavy chains), and other types of fragment as known to one skilled in the art. SEQ ID NOs: 2 and 4 are the amino acid sequences of the heavy and light chains of the anti-RhD monoclonal antibody referred to herein as RhD1 and described befow in further detail SEQ fD NOs: 6 and 8 are the amino acid sequences of the heavy and fight chains of the anti-RhD monoclonal antibody referred to herein as RhD2 and described below in further detail. SEQ ID NOs: 10 and 12 are the amino acid sequences of the heavy and light chains of the 5 anti-RhD monoclonal antibody referred to herein as RhD3 and described below in further detail. The antibodies according to the first aspect of the present invention therefore comprise heavy chain and light chain variable regions having first 10 second and third complementarity determining regions (i.e. CDR1, CDR2 and CDR3) which are identical or substantially identical to the first second and third complementarity determining regions (CDR1, CDF*2 and CDR3) of antibody RhD1,RhD2orRhD3. 15 20 As used herein, two CDRs are "substantially identical" if they have amino acid sequences that preferably are at least 80% identical and/or differ in no more than one amino acid. More preferably the sequences are at least 90% identical and/or differ in no more than one amino acid. Preferably, where amino acid substitutions occur such substitutions are conservative substitutions. Where the CDRs of two antibodies are at least substantially identical, it is reasonable to predict that the resulting antigen binding site of the two antibodies will have similar antigen binding properties. For example, antibodies RhD1 and RhD2 have highly similar CDRs, as can be seen from Figures 1 and 2 (described below in further detail), and both have high binding affinity for the RhD antigen. 25 Most preferabfy, the CDRs of the antibody ar§ identical to those of RftDl, RhD2 or RhD3. As used herein the term "an isolated monoclonal antibody" refers to an 30 antibody which has been produced by monoclonal techniques and which has been isolated from antibodies of other types. In other words, the only other antibodies present will be antibodies produced by ceils of the same cell line (i.e. cells all originating from the same single parent cell) as the cell which produced the monoclonal antibody. This is of course in contrast to, for example, polyclonal antibodies where the antibodies constitute a mixture of different antibodies originating from different plasma cells. fn a preferred embodiment, the isolated anti-RhD monoclonal antibody 5 comprises heavy and light chain variable regions which are at least 80%, more preferably at least 90%, more preferably at least 95%, more preferably at least 98%, most preferably 100% identical to the respective variable regions of the heavy and light chains of the RhD1, RhD2 or RhD3 antibody to which its CDRs are at least substantially identical. Thus, in this embodiment the antibody 10 comprises either: a) a heavy chain variable region which is at least 80%, 90%, 95%, 98%r or 100% jdenticaJ to the variabJe repjon of Sj=Q \D NO: 2 and has first, second and third CDRs which are identical or substantially identical to the 15 respective first, second, and third CDRs of SEQ ID NO: 2, and a light chain variable region which is at least 80%, 90%, 95%, 98%, or 100% identical to the variable region of SEQ ID NO: 4 and has first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 4; or 20 b) a heavy chain variable region which is at least 80%, 90%, 95%, 98%, or 100% identical to the variable region of SEQ ID NO: 6 and has first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 6, and a light chain 25 variable region which is at least 80%, 90%, 95%, 98%, or 100% identical to the variable region of SEQ ID NO: 8 and has first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 8; or 30 c) a heavy chain variable region which is at least 80%, 90%, 95%, 98%, or 100% identical to the variable region of S£Q ID NO: 10 and has first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 10, and a light chain variable region which is at least 80%, 90%, 95%, 98%r or 100% identical to the variable region of SEQ ID NO: 12 and has first, second and third CDRs which are identical or substantially identical to the respective first, second, and third CDRs of SEQ ID NO: 12. 5 Techniques for identifying antibody variable regions and CDRs, comparing and aligning amino acid sequences, and determining the % identity between two amino acid sequences are well known in the art. For example, the CDRs, variable regions, and constant regions of an antibody can be determined using software such as IMGT/V-QUESTtooi 10 (http://imgt.cines.fr/IMGT vquest/share/textes/) using default settings, and/or via comparison with databases of known immunoglobulin sequences such as IMGT/GENE-DB (http://imgt.cines.fr/IMGT GENE-DB/GENEIect?livret=Q) or V-BASE (http://vbase.mrc-cpe.cam.ac.uk/). Amino acid or nucleic acid sequence sequences, whether for whole antibodies or specific parts thereof, can be aligned 15 and their % identity determined using ClustalW (http://www.ebi.ac.uk/Tools/clustaiw/). ClustalW2 (http://www.ebi.ac.uk/Tools/clustalw2/) or GAP (http://genome.cs.mtu.edu/align/alian.html) using default parameters, or using proprietary software such as Vector NTI v. 10.3. 20 In a preferred embodiment, the antibody further comprises a light chain constant domain and at least one heavy chain constant domain. The light chain constant domain may be of either the kappa or lambda type. The heavy chain constant domain is preferably an IgG class constant domain. Thus, in this 25 embodiment the antibody may for example be a Fab' or F(ab')2 fragment, as discussed above, or it may be a whole antibody. If the latter, preferably all the heavy chain constant domains are IgG domains (i.e. the antibody comprises an IgG heavy chain constant region). In a particularly preferred embodiment the constant domain or region is an IgG 1 or IgG 3 constant domain or region. 30 Preferably all constant domains (both light and heavy) are human constant domains. According to a second aspect of the present invention, there is provided an isolated polynucleotide encoding the light and/or heavy chain of an antibody according to the first aspect. 5 As used herein, the term an "isolated polynucleotide" refers to a polynucleotide that has been isolated from a cellular environment (i.e. it is not present in a cell or organism), and it can be in purified form (i.e. substantially free of other polynucleotides, proteins, and cellular components) of form part of composition containing other polynucleotides and/or compounds. The term 10 "encoding a light chain" refers not only to sequences encoding whole light chains, but also to sequences encoding fragments thereof (such as the variable domain only) where the antibody to be expressed is an antibody fragment as described above. Similarly, the term "encoding a heavy chain" refers not only to sequences encoding whole heavy chains, but also to sequences encoding 15 fragments thereof (such as the variable domain only or the variable domain plus one or more but not all of constant domains) where the antibody to be expressed is an antibody fragment as described above. Exemplary nucleic acid sequences include the relevant coding sequences of 20 SEQ ID NOs: 1, 3, 5, 7, 9, and 11, which sequences are the coding sequences for, respectively, amino acid SEQ ID NOs: 2, 4, 6, 8, 10, and 12. Thus, for example, if the antibody comprises identical variable regions to the variable regions of SEQ ID NOs: 2 and 4 (the heavy and light chains of the anti-RhD antibody designated RhD 1), then an exemplary nucleic acid sequence could 25 comprise the sections of SEQ ID NOs: 1 and 3 that encode said variable regions. Alternatively, such nucleic acid sequences could be modified for optimised expression (i.e. transcription and/or translation) in the desired host cell, for example via techniques known to one of skill in the art. For example, optimization of the native nucleic acid sequence may comprise one or more of: 30 optimizing the GC distribution, and AT/GC stretches (to enhance the stability of mRNA); removing inhibitory motifs (such as premature polyA signals); removing cryptic splice sites (to prevent alternative, incorrect splicing of mRNA); optimizing mRNA secondary structure (to avoid tight hairpins possibly stalling translation); optimizing open reading frames (to avoid secondary or alternative reading frames); and optimizing codon usage (to avoid rare codons that can slow down translation). According to a third aspect of the present invention, there is provided an 5 expression system comprising one or more expression vectors and including: a coding sequence encoding the light chain of an antibody according to the first aspect; and a coding sequence encoding the heavy chain of an antibody according to the first aspect. 10 The expression vector(s) may be of any type used in the art, such as for example plasmids and viral vectors. The expression vectors of the present invention are preferably piasmids. In addition to the antibody chain coding sequences, the vector(s) will include the necessary regulatory sequences for 15 proper transcription and translation of the coding sequences in the intended host cell, such as for example a suitable promoter and polyadenylation (polyA) sequence. The vector(s) may further comprise a Kozak sequence for increased efficiency of expression, and/or a sequence encoding for a signal peptide for post translational transport of the antibody chains (for example for secretion of the 20 antibodies). A further preferred feature is the presence of one or more antibiotic resistance genes and/or other forms of selection marker, allowing for selection of cells that have been stably transfected with the vector, and/or that display stronger expression of the antibody coding sequences, as discussed below in more detail. 25 The promters and poly(A) sequences used to drive expression of the light and heavy chain coding sequences may be of any type used in the art. A variety of different promoters and poly(A) seqences are known, the selection of appropriate promoters and poly(A) sequences for use in the chosen host cell 30 being well within the abilities of one of ordinary skill in the art. For example, suitable promoters for use in a mammalian host cell include the SV40 early and late, elgongation factor 1 (EF-1), and cytomegalovirus (CMV) promoters. Suitable poly(A) sequences include those from SV40 poly(A), bovine growth hormone (BGH), thymidin kinase (TK), and human growth hormone (hGH). In a preferred embodiment, the light and heavy chain coqjng sequences are driven by the human elongation factor 1 alpha (hEF-1ct) foromoter and BGH poly(A) sequence. 5 In one embodiment, the expression systery, comprises an expression vector that includes both the coding sequence for the light chain and the coding sequence for the heavy chain. In an alternative embodiment, the light andj heavy chain coding 10 sequences are carried by separate vectors, the expression system comprising: a first expression vector including a coding sequence encoding the light chain of an antibody according to the first aspect; an^ 3 second expression vector .includinp a cooling sequence encoding the heavy chain of an antibody according to the first asp%ct. 15 In this embodiment, one or both of said first and second expression vectors may include a dihydrofolate reductase (ofy,) selection marker. This marker comprises a coding sequence for DHFR, wich is coupled to suitable promoter and polyadenylation sequences, preferably the SV40 early (SV40E) 20 promoter and poly(A) sequences. DHFR allows de novo synthesis of the DNA precursor thymidine. Therefore, by transfecting a host cell-line which is DHFR deficient (i.e. which is itself incapable of producing t)HFR), one can then select for cells which have stably integrated the vector into their genome by growing the cells in a medium deficient in deoxyribonucfeosides and ribonudeosides. 25 Moreover, once the successfully transfected cell^ have been isolated, the expression of the desired coding sequence(s) (i.e. the light and/or heavy chain) can be amplified by using the DHFR inhibitor methotrxate (MTX) which causes some cells to react by amplifying large regions of DNA surrounding the dhfr gene. 30 In a preferred embodiment, one of said first and second expression vectors includes an antibiotic resistance gene (a nucleic acid sequence that imparts resistance to the antibiotic in question) but does not include the DHFR coding sequence, and the other of said expression vectors includes the DHFR coding sequence but does not include a gene providing resistance to the same antibiotic as said antibiotic resistance gene. The antibiotic resistance gene may be of any type used in the art. For example, suitable antibiotic resistance genes for imparting resistance to a mammalian host cell include: aminoglycoside (e.g. 5 neomycin, hygromycin B) resistance genes, such as neomycin phosphotransferase {npt) and hygromycin B phosphotransferase {hpt, hph); aminonucleoside (eg. puromycin) resistance genes such as puromycin N-acetyltransferase (pac); glycopeptide (eg. bleomycin, phleomycin) resistance genes such as the ble gene; and peptidyl nucleoside (eg. blasticidin) resistance 10 genes such as the bis, bsr or bsd genes. As with the dhfr selection marker, the antibiotic resistance gene may as needed be coupled to any suitable promoter and polyadenylation sequences. Preferred are the SV40 early (SV40E) promoter and polyfA) sequences. 15 In a particularly preferred embodiment, the antibiotic resistance gene comprises a neomycin phosphotransferase (NPT) coding sequence. The cells stably transfected with the vector including the NPT coding sequence can then be selected for by growing the cells in a medium containing neomycin, or a neomycin analog such as G418, the toxic effects of which are neutralized by 20 NPT. Thus, the above described embodiment, in which one vector has the dhfr selection marker and the other has the antibiotic selection gene, allows for selection of only those cells which have stably integrated both vectors into their 25 genome by growing the cells in a medium deficient in deoxyribonucleosides and ribonucleosides and containing the relevant antibiotic (such as neomycin or a suitable analogue where the antibiotic resistance gene is the npt gene). Cells that were not transfected or were transfected with only one plasmid will not survive the selection process. Moreover, because the co-transfected plasmids 30 often integrate into one spot of the genome, Subsequent growth of the successfully transfected cells in increasing concentrations of MTX can still be used to effectively amplify expression of the antibody chains encoded by both vectors (i.e. to amplify expression of both the heavy and light chain sequences). ft should be noted that while, in this embodiment, the vector carrying the dhfr selection marker does not include a gene providing resistance to the same antibiotic as the antibiotic resistance gene carried by the other vector, it and indeed both vectors may further comprise a different antibiotic resistance gene 5 providing resistance against a further antibiotic. Again, the additional antibiotic gene may be of any type used in the art. For example, where one but not both vectors carries an NPT coding sequence (providing resistance against neomycin and analogues thereof) both vectors may usefully additionally comprise an ampicillin resistance (AmpR) gene, for the purpose of providing ampicillin 10 resistance when incorporated into a bacterial host cell. Other antibiotic resistance genes that are commonly used to impart resistance in bacterial hosts include: plactamase genes (providing resistance to piactam antibiotics such as ampicillin and other penicillins), such as TEM-1 ^lactamase; penes providing resistance to aminoglycosides such as streptomycin, kanamycin, tobramycin, 15 and amikacin; and tetracycline (e.g. tetracycline, doxycycline, minocycline, oxtetracycline) resistance genes, such as the tetA genes. According to a fourth aspect, the present invention provides a cell transformed with an expression system according to the third aspect or fourth 20 aspects. The host cells for use in the present invention may be of any suitable type. However, in a preferred embodiment the host cell (cell to be transfected) is a eukaryotic cell, more preferably a vertebrate ceil, most preferably a mammalian 25 cell. A variety of suitable mammalian host cells are available, such as are for example listed in US-A1-2003/0175969 referred to above. Preferred mammalian host cells include: all variants of CHO cells, such as CHO K1 and dhfr-deficient CHO (DG44, DXB11); HEK293; BHK; COS-1 and COS-7; NSO; and PER.C6. The preferred host cells are Chinese Hamster Ovary (CHO) cells, in particular 30 dftfr-deficient CHO cells {dfhr- CHO cells). The host cells may be transfected with the expression vectors using standard techniques and transfection conditions, such as are known in the art. Exemplary transfection conditions are provided in the Examples that follow. According to a fifth aspect, the present invention provides a method of manufacturing monoclonal antibodies, comprising cultivating recombinant cells according to the fifth aspect, and recovering the monoclonal antibody from the culture medium. Exemplary growth media and conditions are provided in the 5 Examples that follow, but any suitable growth conditions and commercial or custom growth media can be used, as are routinefy employed in the art. Likewise, any standard technique for purifying secreted antibodies from growth media can be employed, exemplary techniques being again outlined below. 10 According to a sixth aspect, the present invention provides a pharmaceutical composition comprising: a monoclonal antibody according to the first aspect; and a pharmaceutically acceptable carrier. The monoclonal antibodies can be formulated as desired dependent on 15 the intended route of administration. For example, the monoclonal antibodies may be formulated for injection (for example intra-muscularly) analogous to conventional polyclonal anti-D formulations. Exemplary dosages range from 150 to 300 micrograms (as measured by agglutination titer, as described below in further detail). Exemplary carriers include: phosphate-buffered saline; and 20 glycine saline buffer. The composition may comprise monoclonal antibodies of a single type only (i.e. the only antibodies present in the composition are antibodies produced by cells of the same cell line). Alternatively, the composition may comprise a 25 combination of more than one type of monoclonal antibody. For example, the composition could comprise two or more distinct types of monoclonal antibodies that are in accordance with the first aspect of the invention, such as a combination of two or all three of monoclonal antibodies RhD1, RhD2 and/or RhD3. Alternatively or additionally, the composition could comprise, in addition 30 to monoclonal antibodies according to the first aspect of the present invention, other anti-RhD monoclonal antibodies as for example are known from the art. In a preferred embodiment, the composition comprises at least one monoclonal antibody that has an IgG 1 constant domain or region, and at least one monoclonal antibody that has an IgG 3 constant domain or region. Where the composition comprises a combination of more than one type of monoclonal antibody, it is preferred that the composition comprises no more than 50 different types of monoclonal antibody. More preferably, the composition 5 comprises at most 25, 20, 15, 10 or 5 different types. According to a seventh aspect, the present invention provides a method of inhibiting or preventing immunization of a RhD-negative human patient against RhD-positive blood, comprising administering a prophylactically effective amount 10 of a monoclonal antibody according to the first aspect or pharmaceutical composition according to the sixth aspect. Specific indications and/or circumstances in which the monoclonal antibodies may be administered correspond to those for which the existing anti-15 RhD polyclonal antibodies are administered. According to an eighth aspect, the present invention provides a monoclonal antibody according to the first aspect, or a pharmaceutical composition according to the sixth aspect, for use in a method of inhibiting or 20 preventing immunization of a RhD-negative human patient against RhD-positive blood. According to a ninth aspect, the present invention provides the use of a monoclonal antibody according to the first aspect in the manufacture of a 25 medicament for inhibiting or preventing immunization of a RhD-negative human patient against RhD-positive blood. The invention is further illustrated in the following non-limiting Examples, with reference also to the accompanying drawings in which: 30 Figure 1 is an alignment of amino acid sequences of the heavy chains of monoclonal antibodies RhD1, RhD2 and RhD3, in which the variable regions have been underlined and the complementarity determining regions highlighted in bold and shaded; Figure 2 is an alignment of amino acid sequences of the light chains of monoclonal antibodies RhD1, RhD2 and RhD3, in which the variable regions have been underlined and the complementarity determining regions highlighted 5 in bold; Figure 3 is a map of plasmid vector pCB3; Figure 4 is a map of plasmid vector pCB11; 10 Figure 5 is a map of pCB3 containing an anti-RhD antibody heavy chain (RhD HC) coding sequence; and Figure 6 is a map of pCB11 containing an $nti-RhD antibody light chain 15 (RhD LC) coding sequence; Figure 7 is an example of a dose-response