WO1989002443A1 - HUMAN ANTI-Rh(D) MONOCLONAL ANTIBODIES - Google Patents
HUMAN ANTI-Rh(D) MONOCLONAL ANTIBODIES Download PDFInfo
- Publication number
- WO1989002443A1 WO1989002443A1 PCT/GB1988/000757 GB8800757W WO8902443A1 WO 1989002443 A1 WO1989002443 A1 WO 1989002443A1 GB 8800757 W GB8800757 W GB 8800757W WO 8902443 A1 WO8902443 A1 WO 8902443A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- monoclonal antibody
- reagent
- antibody
- cells
- monoclonal
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/34—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood group antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates to human monoclonal antibodies to the Rh(D) antigen of human red blood cells.
- it relates to such antibodies of the IgG1 sub-class which may be used to detect not only the normal Rh(D) antigen, but also important variants of this antigen.
- Rh(D) antigen is responsible for some of the most severe reactions following transfusion to a patient with corresponding antibody. Since an Rh(D-) individual with anti-Rh(D) who receives Rh(D+) blood is liable to suffer substantial red blood cell (RBC) destruction due to the Rh(D) phenotype incompatibility, blood of donors and blood transfusion recipients is routinely classified as Rh(D+) or Rh(D-) by agglutination tests with anti-Rh(D) antibody.
- RBC red blood cell
- Rh phenotype of RBCs is commonly further defined with reference to the Fisher-Race system, which is based on the assumption that the inheritance of the Rh antigens is determined by three pairs of allelic genes, C-c, D-d and E-e, acting at very closely linked loci.
- a person may inherit a set of three Rh genes from each of his parents (i) C or c , (ii) D or d , (iii) E or e (no d antigen has as yet been identified, but the symbol 'd' is used to indicate the presence of a gene, allelic to the D gene, which does not produce D antigen).
- an Rh(D+) person may inherit CDe from one parent and cde from the other.
- Table 1 The frequencies of the commonest Rh gene combinations as determined with reference to the Fisher-Race system for an English population, together with the 'short symbols' which are used, particularly in speech, are given in Table 1 below.
- Rh(D) antibody for Rh-typing of RBCs, such antibody is also importantly required for passive immunisation of Rh(D-) mothers to prevent haemolytic disease of the newborn (HDN).
- This condition arises in newborn Rh(D+) infants of Rh(D-) mothers previously sensitized to Rh(D) antigen as a result of IgG anti-Rh(D) antibodies crossing the placenta during pregancy and causing foetal RBC destruction.
- Sensitization of the Rh(D-) mother to Rh(D) antigen may have occurred at the birth of an earlier Rh(D+) child due to some foetal RBCs entering the maternal circulation and being recognised by the maternal immune system.
- anti-Rh(D) antibody for use in both Rh-typing of RBCs and passive immunisation of Rh(D-) mothers is largely obtained directly from female donors immunised during pregnancy or from immunised male volunteers.
- the success of the programme of post-partum prophylactic administration of human anti-Rh(D) immunoglobulin to Rh(D-) women has, however, resulted in a dramatic reduction in the number of naturally alloimmunised women (Urbaniak, S.J., "RhD haemolytic disease of the newborn: the changing scene", Br. Med. J. (1985)
- Rh(D+) and Rh(D-) on the basis of the apparent presence or absence of Rh(D) antigen on the RBCs as indicated by agglutination tests with anti-Rh(D).
- a small number of persons with apparently Rh(D-) blood have RBCs that are not directly agglutinated by anti-Rh(D) during such routine testing, but that do react when the D-typing test is performed using selected anti-Rh(D) reagents by the indirect antiglobulin test. Cells thus identified are designated D u .
- the frequency of the D u phenotype is about 0.2% overall, 0.6% among Caucasians, and about 1.5% of all Rh(D-) gravid women.
- At least three different mechanisms may be responsible for the expression of the D u phenotype: (1) hereditary absence of a portion of the complete Rh(D) antigen, (2) gene interaction with suppression of D by C in the trans position, and (3) a D gene producing a weak antigen.
- hereditary absence of a portion of the complete Rh(D) antigen (2) gene interaction with suppression of D by C in the trans position, and (3) a D gene producing a weak antigen.
- reports first appeared of the presence of anti-Rh(D) in individuals of the D u phenotype following blood transfusion with Rh(D+) blood or pregnancy resulting in the birth of a Rh(D+) infant.
- Rh(D+) parts of the Rh(D) antigen are missing from the RBCs.
- Rh(D+) RBCs carrying the complete Rh(D) antigen persons carrying an incomplete Rh(D) antigen on their RBCs are capable of making alloanti-D against the Rh(D) antigen portion they lack.
- the blood of such individuals is called D variant when the RBCs react directly with routine anti-Rh(D) reagents or D u variant when the cells react only by the indirect antiglobulin technique.
- D u variant women who give birth to an Rh(D+) infant may also benefit from postpartum anti-Rh(D) treatment to reduce the risk of HDN (White, C.A. et al. (1983) Am. J. Obstet. Gynecol. 145, 1069-1073).
- Anti-sera capable of distinguishing D and D u variant RBCs are not widely available.
- anti-Rh(D) monoclonal antibodies with a range of binding specif icities for D and D u variant RBCs is seen as useful in enabling the more ready identification and categorisation of individuals possessing such cells (especially D or D u variant pregnant females who are suitable candidates for prophylactic anti-Rh(D) treatment) as well as for providing further structural information on the Rh(D) antigen complex.
- Human monoclonal anti-Rh(D) antibody production has previously been achieved by:-
- EBV-transformed LCL Epstein Barr virus transformed B lymphocyte cell lines
- RBCs as D-positive, D u or D-negative and may also find use in identifying individuals of the D IV type.
- an anti-Rh(D) monoclonal antibody of the present invention will be combined with one or more additional anti-Rh(D) monoclonal antibodies having one or more additional binding specificities, including anti- D IV activity, e.g.
- an anti-Rh(D) monoclonal antibody of the present invention especially the monoclonal antibody of the cell line hereinafter designated B7, may be blended with an IgG1 or IgG3 anti-Rh(D) monoclonal antibody having the following binding characteristics:
- a monoclonal antibody of the present invention may also be of particular value for use in an anti-Rh(D) typing reagent additionally including an IgM anti-Rh(D) with weak or no anti-D u activity, i.e. insufficient activity against D u cells to be able to reliably distinguish such cells from D-negative cells in a conventional agglutination test.
- an anti-Rh(D) typing reagent additionally including an IgM anti-Rh(D) with weak or no anti-D u activity, i.e. insufficient activity against D u cells to be able to reliably distinguish such cells from D-negative cells in a conventional agglutination test.
- Such a combination anti-Rh(D) reagent will contain the following antibody components:
- an IgM monoclonal antibody as hereinbefore defined preferably an IgM monoclonal anti- Rh(D) selected from the monoclonal IgMs of the deposited hybridoma cell lines MAD-2 (ECACC 86041803) and FOM-1 (ECACC 87021301) , which form inter alia the subject matter of published European Patent Application 0251440;
- an antibody of the present invention especially the monoclonal antibody of the cell line hereinafter designated B7; and optionally (c) one or more further IgG monoclonal anti-Rh(D) antibodies which individually exhibit activity with D u red cells by the indirect antiglobulin test, such that the blended reagent reacts by the same test with D u , D IV , D V and D VI cells.
- Rh-typing is carried out with such a reagent having the binding capability defined in
- D-positive cells will firstly be directly agglutinated by the IgM anti-Rh(D).
- the remaining non-agglutinated cells may then be subsequently divided into truly D-negative and D u cells by addition of conventional Coomb's reagent for an antiglobulin test, whereupon D u cells binding IgG antibody will be agglutinated and thus distinguished.
- the monoclonal anti-Rh(D) antibodies of the invention can be made by conventional methods known for the production of monoclonal antibodies and in particular by the culture of EBV-transformed human B-lymphocytes selected on the basis of secretion of anti-Rh(D) immunoglobulin having the characteristics set out above for the required antibodies.
- the culture supernatants so produced constitute a further feature of the present invention.
- Table III gives the results of indirect anti-globulin tests (IAG) tests (3% RBCs in low ionic strength saline) with untreated supernatants from continuous cultures of the above-mentioned specific clones.
- IAG indirect anti-globulin tests
- the degree of agglutination was graded in conventional manner on a scale of 0 to 6.
- Anti-Rh(D) 3 .3Iu/ml
- IgG 0 . 8 ug/ml
- a method of Rh-typing of RBCs wherein an aqueous solution of a monoclonal anti-Rh(D) immunoglobulin of the present invention is employed.
- the monoclonal immunoglobulin is preferably contained in a culture supernatant which may be used directly or, more usually, after dilution.
- Suitable diluents include physiological saline or phosphate buffered saline advantageously containing bovine serum albumin and a surfactant or suspending agent such as Tween 80 or methyl cellulose.
- Monoclonal antibodies of the present invention may also find use in the provision of a prophylactic reagent for use in post-partum prevention of HDN.
- a monoclonal IgG1 antibody as hereinbefore described for use in passive immunisation of an Rh(D-) or D or D u variant mother after the birth of an Rh(D+) child.
- a monoclonal antibody of the present invention will be blended with one or more further anti-Rh(D) monoclonal antibodies with different characteristics, e.g. one or more anti-Rh(D) monoclonal antibodies of the IgG3 sub-class and/or capable of exhibiting activity against D IV cells.
- a sterile solution of an antibody according to the present invention suitable for human injection may be formulated in any physiologically acceptable aqueous medium, for example isotonic phosphate-buffered saline or serum.
- such an antibody may be supplied in a freeze-dried formulation ready for reconstitution prior to use.
- Example 1 Further details of the preparation of this deposited cell line and identifying characteristics of its continuous culture supernatant are provided in Example 1 of the following non-limiting Examples.
- the donor employed was a male, initially immunised by transfusion in 1966, boosted 6 times since and last boosted 13 days before donating a "buffy coat” fraction (white cells) in 1985 when his serum anti-D level was 318lU/ml.
- Peripheral blood mononuclear cells from the chosen donor were separated on Lymphoprep (Nyegaard and Co) incubated in the presence of EBV (1 ml culture supernatant from filtered mycoplasma free B95-8 cell line per 10 7 cells) at 37°C for 1 hour and washed in phosphate-buffered saline (PBS).
- EBV EBV (1 ml culture supernatant from filtered mycoplasma free B95-8 cell line per 10 7 cells
- IgG in culture supernatants Anti-D activity in the supernatants was quantified against British national standards by Auto Analyser. The quantitative estimation of IgG was performed by ELISA (modification of the method of Wakefield et al. in Clin. Chim. Acta. (1982) 123, 303-310) with at least eight determinations for each supernatant. Coating antibody (affinity purified goat anti-human IgG (Sigma)) was used at 1/200 in 0.05M carbonate buffer pH 9.6. Supernatants and standard (purified human IgG (Sigma)) were diluted in RPMI 1640 + 10% FCS. Peroxidase-conjugated goat anti-human IgG (Sigma) was diluted 1/500 in PBS + 0.05% Tween 20 and the substrate was TMB (3,3', 5,5'-tetramethyl benzidine).
- An immunodot assay (McDougal et al. (1983) 63, 281-290) was used to determine the reaction of the monoclonal anti-Rh(D) antibodies absorbed to nitrocellulose with anti-IgG, anti-IgM, anti- kappa and anti-lambda antiserum (Serotec); positive reactions were detected with peroxidase-conjugated anti-sheep IgG (Serotec) followed by colour development with 4-chloro-1-naphthol. The IgG subclass was evaluated by agglutination of anti-Rh(D) coated
- RBCs by monoclonal anti-subclass antibodies (Unipath).
- RBCs were coated with the monoclonal anti- Rh(D) antibodies and agglutination assessed using panels of Gm allotyping reagents (Birmingham or Amsterdam).
- Tissue Type HLA A 1,3
- an anti-Rh(D) monoclonal antibody according to the invention e.g. B7
- a further IgG anti-Rh(D) monoclonal antibody for example B11 of our copending International patent application No. of even date herewith claiming priority from GB-A 8722018.
- the final blend is 1:1:1 B11:B7: diluent.
- This blend can be used in all manual tests for D and D u typing, e.g. microtitre, microplate, IAG.
- a blend of 1:1:2 B11:B7: diluent may also be used.
- This blend may be used, for example, in a Technicon autogrouper 16C
- the solution For D-Phenotyping (D-positive v. D-negative) the solution comprises 1:1000 blend: diluent, and for D u determinations (D u v. D-negative) the solution comprises 1:5 blend: diluent.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK069690A DK69690A (da) | 1987-09-18 | 1990-03-16 | Humane anti-rh(d) monoklonale antistoffer |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB878722020A GB8722020D0 (en) | 1987-09-18 | 1987-09-18 | Human anti-rh(d)monoclonal antibodies |
GB8722020 | 1987-09-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1989002443A1 true WO1989002443A1 (en) | 1989-03-23 |
Family
ID=10624026
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1988/000757 WO1989002443A1 (en) | 1987-09-18 | 1988-09-16 | HUMAN ANTI-Rh(D) MONOCLONAL ANTIBODIES |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0378572A1 (ja) |
JP (1) | JPH03502401A (ja) |
AU (1) | AU2383288A (ja) |
DK (1) | DK69690A (ja) |
GB (1) | GB8722020D0 (ja) |
WO (1) | WO1989002443A1 (ja) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990011090A1 (en) * | 1989-03-17 | 1990-10-04 | Central Blood Laboratories Authority | Pharmaceutical compositions |
WO1991003492A1 (en) * | 1989-09-01 | 1991-03-21 | Central Blood Laboratories Authority | MODIFIED HUMAN ANTI-Rh(D) ANTIBODIES |
EP0576093A1 (en) * | 1992-06-26 | 1993-12-29 | Association Pour L'essor De La Transfusion Sanguine Dans La Region Du Nord | Human monoclonal anti-Rhesus (D) antibodies and cell lines producing same |
FR2692786A1 (fr) * | 1992-06-26 | 1993-12-31 | Aetsrn | Anticorps monoclonaux humains anti-Rhésus D et lignées cellulaires les produisant. |
US5665356A (en) * | 1987-09-18 | 1997-09-09 | The National Blood Authority | Human anti-Rh (D) monoclonal antibodies |
EP1518864A2 (fr) | 2000-04-12 | 2005-03-30 | Laboratoire Français du Fractionnement et des Biotechnologies | Anticorps monoclonaux anti-rhesus D |
US8198415B2 (en) | 2004-07-20 | 2012-06-12 | Symphogen A/S | Anti-rhesus D recombinant polyclonal antibody |
US8288109B2 (en) | 2004-07-20 | 2012-10-16 | Symphogen A/S | Procedure for structural characterization of a recombinant polyclonal protein or a polyclonal cell line |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU622417B2 (en) * | 1987-09-18 | 1992-04-09 | National Blood Authority | Human anti-rh(d) monoclonal antibodies |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1985002413A1 (en) * | 1983-11-28 | 1985-06-06 | The Board Of Trustees Of The Leland Stanford Jr. U | HUMAN MONOCLONAL ANTIBODY AGAINST Rh(D) ANTIGEN AND ITS USES |
JPS60136599A (ja) * | 1983-12-26 | 1985-07-20 | Isao Ono | モノクロ−ナル抗体 |
-
1987
- 1987-09-18 GB GB878722020A patent/GB8722020D0/en active Pending
-
1988
- 1988-09-16 WO PCT/GB1988/000757 patent/WO1989002443A1/en not_active Application Discontinuation
- 1988-09-16 AU AU23832/88A patent/AU2383288A/en not_active Abandoned
- 1988-09-16 JP JP63507469A patent/JPH03502401A/ja active Pending
- 1988-09-16 EP EP88908268A patent/EP0378572A1/en not_active Withdrawn
-
1990
- 1990-03-16 DK DK069690A patent/DK69690A/da not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1985002413A1 (en) * | 1983-11-28 | 1985-06-06 | The Board Of Trustees Of The Leland Stanford Jr. U | HUMAN MONOCLONAL ANTIBODY AGAINST Rh(D) ANTIGEN AND ITS USES |
JPS60136599A (ja) * | 1983-12-26 | 1985-07-20 | Isao Ono | モノクロ−ナル抗体 |
Non-Patent Citations (3)
Title |
---|
Chemical Abstracts, vol. 104, no. 17, 28 April 1986, (Columbus, Ohio, US) see page 538, abstract no. 147012e & JP-A-60136599 (MITSUBISHI CHEMICAL INDUSTRIES CO. LTD) 20 July 1985 * |
Chemical Abstracts, vol. 107, no. 9, 31 August 1987, (Columbus, Ohio, US) G. MacDonald et al.: "Production and characterization of human-human and human-mouse hybridomas secreting Rh (D)-specific monoclonal antibodies" see page 522 * |
Journal of Immunoglogical Methods, vol. 104, 1987, Elsevier Science Publishers B.V. M.D. Melamed et al.: "Requirements for the establishment of heterohybridomas secreting monoclonal human antibody to rhesus (D) blood group antigen", pages 245-251 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5665356A (en) * | 1987-09-18 | 1997-09-09 | The National Blood Authority | Human anti-Rh (D) monoclonal antibodies |
WO1990011090A1 (en) * | 1989-03-17 | 1990-10-04 | Central Blood Laboratories Authority | Pharmaceutical compositions |
WO1991003492A1 (en) * | 1989-09-01 | 1991-03-21 | Central Blood Laboratories Authority | MODIFIED HUMAN ANTI-Rh(D) ANTIBODIES |
US5851524A (en) * | 1992-06-26 | 1998-12-22 | Association Pour L'essor De La Transfusion Sanguine Dans La Region Du Nord | Human monoclonal anti-rhesus (D) antibodies and cell lines producing same |
WO1994000561A1 (en) * | 1992-06-26 | 1994-01-06 | Association Pour L'essor De La Transfusion Sanguine Dans La Region Du Nord | Human monoclonal anti-rhesus (d) antibodies and cell lines producing same |
FR2692786A1 (fr) * | 1992-06-26 | 1993-12-31 | Aetsrn | Anticorps monoclonaux humains anti-Rhésus D et lignées cellulaires les produisant. |
EP0576093A1 (en) * | 1992-06-26 | 1993-12-29 | Association Pour L'essor De La Transfusion Sanguine Dans La Region Du Nord | Human monoclonal anti-Rhesus (D) antibodies and cell lines producing same |
EP1518864A2 (fr) | 2000-04-12 | 2005-03-30 | Laboratoire Français du Fractionnement et des Biotechnologies | Anticorps monoclonaux anti-rhesus D |
EP2341078A2 (fr) | 2000-04-12 | 2011-07-06 | LFB Biotechnologies | Anticorps monoclonaux anti-rhesus D |
EP2947099A1 (fr) | 2000-04-12 | 2015-11-25 | Laboratoire Français du Fractionnement et des Biotechnologies | Anticorps presentant une activite adcc amelioree |
US8198415B2 (en) | 2004-07-20 | 2012-06-12 | Symphogen A/S | Anti-rhesus D recombinant polyclonal antibody |
US8288109B2 (en) | 2004-07-20 | 2012-10-16 | Symphogen A/S | Procedure for structural characterization of a recombinant polyclonal protein or a polyclonal cell line |
US9029091B2 (en) | 2004-07-20 | 2015-05-12 | Symphogen A/S | Procedure for structural characterization of a recombinant polyclonal protein or a polyclonal cell line |
Also Published As
Publication number | Publication date |
---|---|
GB8722020D0 (en) | 1987-10-28 |
AU2383288A (en) | 1989-04-17 |
DK69690A (da) | 1990-05-17 |
EP0378572A1 (en) | 1990-07-25 |
JPH03502401A (ja) | 1991-06-06 |
DK69690D0 (da) | 1990-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kumpel et al. | Human monoclonal anti‐D antibodies. I. Their production, serology, quantitation and potential use as blood grouping reagents | |
Brindley et al. | Role of host antibody in the chemotherapeutic action of praziquantel against Schistosoma mansoni: identification of target antigens | |
US7429647B2 (en) | Polypeptides capable of forming antigen binding structures with specificity for the Rhesus D antigens, the DNA encoding them and the process for their preparation and use | |
US5665356A (en) | Human anti-Rh (D) monoclonal antibodies | |
DK154769B (da) | Monoklonalt antistof, fremstilling heraf, hybridomacellelinie til anvendelse ved fremstilling heraf samt fremgangsmaader til anvendelse heraf | |
Hough et al. | Anti-idiotype sera raised against surface immunoglobulin of human neoplastic lymphocytes. | |
WO1989002443A1 (en) | HUMAN ANTI-Rh(D) MONOCLONAL ANTIBODIES | |
EP0383777B1 (en) | HUMAN ANTI-Rh(D) MONOCLONAL ANTIBODIES | |
Zola et al. | Monoclonal antibodies against antigens of the human platelet surface: preparation and properties | |
AU607134B2 (en) | Human anti-rhesus D producing heterohybridomas | |
Gathings et al. | Immunofluorescence studies on the expression of VH a allotypes by pre‐B and B cells of homozygous and heterozygous rabbits | |
US5496548A (en) | Human anti-RH(D) monoclonal antibodies, cell lines and methods of use of antibodies in immunoassays | |
AU623345B2 (en) | Human anti-rh(d) monoclonal antibodies | |
AU622417B2 (en) | Human anti-rh(d) monoclonal antibodies | |
McCann‐Carter et al. | The production and evaluation of two human monoclonal anti‐D antibodies | |
EP0489771B1 (en) | MODIFIED HUMAN ANTI-Rh(D) ANTIBODIES | |
Del Aguila et al. | Human monoclonal antibodies against the Rhesus D antigen from women with severe Rh immunization submitted to high-dose intravenous immunoglobulin treatment | |
WO1991004277A1 (en) | Monoclonal antibodies specific to cytomegalovirus glycoprotein | |
Klein | Immunological markers of human mononuclear cells | |
OHNO et al. | A Mouse Monoclonal Antibody Reactive Preferentially with Human IgM λ | |
Gadd | Analysis of acute mycloid leukaemia cell surface antigens with monoclonal antibodies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU DK JP KR US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1988908268 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1988908268 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1988908268 Country of ref document: EP |