GB2127434A - A human monoclonal antibody against Rhesus D antigen - Google Patents
A human monoclonal antibody against Rhesus D antigen Download PDFInfo
- Publication number
- GB2127434A GB2127434A GB08226513A GB8226513A GB2127434A GB 2127434 A GB2127434 A GB 2127434A GB 08226513 A GB08226513 A GB 08226513A GB 8226513 A GB8226513 A GB 8226513A GB 2127434 A GB2127434 A GB 2127434A
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- GB
- United Kingdom
- Prior art keywords
- rhesus
- human monoclonal
- antigen
- monoclonal antibody
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
- 102100027544 Blood group Rh(D) polypeptide Human genes 0.000 title claims description 11
- 101000580024 Homo sapiens Blood group Rh(D) polypeptide Proteins 0.000 title claims description 11
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 36
- 210000003743 erythrocyte Anatomy 0.000 claims description 13
- 238000012360 testing method Methods 0.000 claims description 12
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 230000035935 pregnancy Effects 0.000 claims description 3
- 231100001261 hazardous Toxicity 0.000 claims description 2
- 238000002649 immunization Methods 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 5
- 238000001727 in vivo Methods 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000000427 antigen Substances 0.000 description 19
- 102000036639 antigens Human genes 0.000 description 18
- 108091007433 antigens Proteins 0.000 description 18
- 239000006228 supernatant Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 230000004520 agglutination Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229930186657 Lat Natural products 0.000 description 1
- 229910000694 Nambé Inorganic materials 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/80—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
This invention relates to a cloned, EB virus-transformed lymphoblastoid cell line and a technique for preparing the same. The cell line is capable of producing quantities of an IgG anti Rhesus D antibody useful as a standardised reagent in cross matching laboratories and as an in vivo agent for the prevention of rhesus disease in the newborn.
Description
SPECIFICATION
A human monoclonal antibody against Rhesus D antigen
This invention relates to a human monoclonal antibody against Rhesus D antigen and is specifically concerned with a cloned, Epstein-Barr (EB) virustransformed, lymphoblastoid cell line which grows well in culture and produces a monoclonal antibody in the supernatant culture medium.
Several attempts have been made in the pastto develop human antibodies against the Rhesus D antigen. Thus, Koskimies has reported in Scand. J.
Immunol, 11, 73-77 (1980) a human lymphoblastoid cell line which is stated to produce specific antibody against Rh-Antigen D. The cell line is stated to have been established by EB virus infection and to have produced specific antibody of the IgG class, namely
IgGI sub-class and also non-specific IgM and IgG. It appears however from study of the results of
Koskimies that the cell line was in fact uncloned.
Boylston and his co-workers have reported in
Scand. J. Immunol 12,355-358(1980) the production of human lgM Anti-Din tissue culture by EB-Virustransformed Lymphocytes. However, here again the cel Is would appear to have been uncloned.
It has been shown that so-called Rhesus disease in new born infants is caused bythe destruction offoetal
D positive red blood cells by maternal anti D antibody during pregnancy. At present, susceptible mothers are prevented from making antibody by the administration of D antibody which is made from the serum of mothers of affected babies or immunised male volunteers. Anti Dfrom these sources is also used for routine red cell D antigen typing.
The present invention is based on the discovery of a techniqueforpreparing EBvirus-transformed human cell lines and cloning these cell lines to form a cloned,
EB virus-transformed, lymphoblastoid cell line, referred to herein as Kdl, which grows well in culture and produces useful amounts of human monoclonal antibody in the supernatant culture medium. The invention therefore also covers the EB virus-transformed human monoclonal cell line and the monoc tonal antibody produced therefrom.
The human monoclonal antibody is ofthe lgG class with klight chains, and is directed againstthe Rhesus
D antigen on human rhesus positive red blood cell membranes. The antibody agglutinates D positive red blood cells at a titre of 1:256 in an indirect antiglobulin test. It is believed to be useful in routine red cell D antigen typing procedures and, also, it is believed thatthe antibody will be useful in the prevention of Rhesus disease of the newborn. Since the material K4/l is a human antibody it may be used in a prophylactic procedure in substitution for the procedure referred to above of administering the antibody from the serum of mothers of affected babiesorimmunised male volunteers.
Fora better understanding ofthe invention, one particular embodiment ofthe method ofthe invention is now described.
In orderto make a human monoclonal antibody to the Rhesus D blood group antigen, buffy coat cells were obtained from a male volunteer who had been boosted with D antigen 1-2 weeks previously. The peripheral blood mononuclear cells (PBM) from this individual were frozen in aliquots of 5 x 107 cells per vial and used for all further experiments.
B cells were enriched from PBM by E-rosetting of T cells followed by removal ofthe E-rosetted cells by spinning them over a percoll gradient. The anti
D-producing cells in the enriched B cell population were then rosetted with a 2% suspension of papaintreated -D- red cells, and separated from the nonrosetted population in the same way. Around 1% of the enriched B cells were found to form these rosettes. The separated, rosetted cells were infected with EB virus and plated out into 0.2 ml volumes in round-bottom tissue culture wells at a concentration of 103 cells per well. 104 allogeneic, X-irradiated (2000 R) PBM cells were added to each well as a feeder layer.
After 3 weeks in culture, the wells were examined under an inverted microscope. 26 out of 98 wells contained actively proliferating foci of cells. The supernatant medium from these wells was tested for anti Rhesus D activity by agglutination of papaintreated Rhesus D positive cells. 7 out of the 26 su pernatants were positive, and one of these (K4) was strongly positive.
One month afterthe start of the experiment, K4 cells were cloned by limiting dilution on a feeder layer of allogenic PBM (1 04/well). lOx 98 well plates were set up. After 3 weeks in culture 70 wells contained actively profilerating cells. The supernatants were tested and all were found to be positive.
Details of tests carried out are given in the attached two tables.
Brief explanations ofthesetables and of the meaning ofthevarious results are now given.
This print takes account of replacement documents later filed to enable the application to comply
with the formal requirements of the Patents Rules 1978.
TABLE 1
REACTIVITY OF E, /1 SUPERNATANT WITH RHESUS D POSITIVE RED BLOOD CELLS
Dithiothreitol Dilution: 1:2 1:4 1:8 1:16 1:32 1:64 1:128 1:256 1:500 1:1000 1:2 1:4 1:8 1:16 1:32 1:64 1:128 1:256 1:500 1::1000 IAT K4/1 ++++ ++++ ++++ +++ +++ +++ ++ # - - +++ +++ +++ ++++ ++++ ++ + # - Control - - - - - - - - - - ++ + - - - - - - - Albumin K4/1 c c +++ +++ +++ ++ ++ # - - +++ +++ +++ ++ ++ - - - - Control - - - - - - - - - - + - - - - - - - - Saline K4/1 - - - - - - - - - - - - - - - - - - - Control - - - - - - - - - - +++ # - - - - - - - - C= Visible clumping. Not examined microscopically.
+++±+= Degrees of red cell agglutination assessed microscopically I.A.T.= Indirect antiglobulin test.
Table 2
Patients Name ---------------------------------------------------------------- Hosp. No. ------~ Room No ---------------------
Doctor------------------------------------------------------------------------
Age ---------- Racial Origin ------------- Sex -------
Group ------------- Rh------------------------------------------------
Direct Coombs Profile: : Polyspecific AHS- Anti-lgG
Anti-Complement- Anti- C3d
Date Specimen Drawn-----------------------------------------------------------
Date of Testing ------------------------------------------
Antibody Identified ---------------------------------------------------------- ------------------------------------------------------------------------------
Comments --------------------------------------------------------------------- ------------------------------------------------------------------------------ ------------------------------------------------------------------------------
Technologist ----------------------------------------------------------------- Monoclonal Anti-D TABLE 2 @(V=Visible agglutination)
EWS KIDD DUFFY KIDD i- lems MNS P r (rpeciall Test Rem ~ ~ ~ ~ P"ti4en IRes- = Typing ults Cell NJrlOrer | rGyeone' > D C E | c | e | f | C K | k ~ + Xgl n X Le' Lea S | S M N P Luz Cel 191 Nambe, tyne No. 4 2 11072 | RIRl + + 0 0 '-O + | 0 | 0 < + + + | + + + 0 + + 0 + + 0 3g(a+) 1 V 2 41351 | R1R1 + + 0 + | | | | + + + | + + + 0 + + 0 + + sg(a+) 2 V 5 Kt "T 6 t-o+ 7 + O i +lol+ + + 8 81482 tr rr 0 | 0 z | + | + | + | + |+ + + |+ + lo + |+ + lo + | | 8 9 81439 | 0 0 0 + + + 0 0 + 0 + + + + 0 + + 0 + 0 + 0 81439 rr 0 0 It 0 | + | + | + | 0 t + + | + + 0 + 0 + + jo 0 + | 0 . | | 9 10 11 81C81rr ololol+l+l+lo ol+ 453 +lo +lo + +lo 0 Sd(a-)I- II Patient I I~L~ All Panel A Cells are positive forthe following
antigens unless otherwise noted on the grid ofthe
ANTIGRAM Antigen Profile P + P + pk (Tja), Vel, Ge, Yta, I, U, Kpb Lub Jsb
All Panel A cells are negative with sera detecting cells of Miltenbergerclasses I thru IV and negative for the low frequency antigens, Bua, Wra, Dia, Kpa, Jsa and V unless otherwise noted on the grid ofthe
ANTI GRAM Antigen Profile.
Detailed information is provided on the "special type" marked with an asterisk(*). Please refertothe special insert (Reference Point) provided with this panel.
Ortho Diagnostic Systems Inc.
All Panel A cells are positive for the following antigens unless otherwise noted on the grid of the
ANTIGRAM Antigen.
Profile: P + P1 + Pk(Tis), Vel, Ge, Yta, I, U, Kpb, Lub, Jsb.
All Panel A cells are negative with sera detecting cells of Miltenberger classes I through IV and negative for the low frequency antigens, Bua, Wra, Dia, Kpa, Jsa and Vunless otherwise noted on the grid of the ANTIGRAM Antigen Profile.
Detailed information is provided on the "special type" marked with an asterisk(*). Please refer to the special insert (Reference Point) provided with this panel.
* Trademark
k4/I supernatant and a control AB serum (which contained no anti D antibody) were tested in parallel both in saline and in the presence of dithiothreitol.
Dithiothreitol inactivates IgM antibody andthus negative results in this set of tests with positive
results in saline would indicate the presence of an
IgM anti D antibody. Positive results in both dithiothreitol and in saline indicate a non-lgM (probable IgG) class of antibody. An indirect antiglobulin test (IAT) and tests for agglutination of Rhesus D positive red blood cells in saline and in albumin were
Panel A Lot No. RA177
Exp Date lS JUL 1982
Reagent Red Blood Calls Resolve Panel A
Antigram* Antigen Profile carried out on doubling dilutions ofthe K4/l supernatant and the control serum (dilutions 1:2-1:1,000).
The results in Table 1 show that K4/l supernatant contains an antibody which agglutinates Rhesus D positive red blood cells in the lATto a titre of 1:256.
The results of the lATs carried out in saline and in the presence of dithiothreitol are similar, indicating that Kdl antibody is not an Ig M antibody. Further results show that Kdjl antibody agglutinates Rhesus D positive red blood cells in albumin but not in saline alone. These results are the expected findings for an
IgG anti D antibody.
Table 2 shows the results of the screening of K4/I antibody against a panel of red blood cells of various genotypes in order to assess its specificity. The left-hand sideofthetableshowsthe red cell antigens expressed on the various cells contained in the panel.
The results of the tests on K,/l antibody are on the right-hand side of the table, and show that the antibody only reacts with those cel Is which express the Antigen (R1WR1, R1R1, R2R2, Ror). None of the cells which lack the D antigen (r'r, r"r, rr) is agglutinated by the antibody. The reaction of K4/I antibody with Kell, Duffy, Kidd,X-linked, Lewis, MNS,
P and Lutheran antigens can also be excluded bythe reaction pattern given. These results clearly indicate that K4/l antibody reacts only with the D antigen on D positive red blood cells.
A cloned, EB vi rus-tra nsformed lymphoblastoid cell line which produces useful quantities of an IgG anti Rhesus D antibody has been developed. In a routine series of tests the antibody reacts in the predicted way, identical to that of the polyclonal anti
D antisera which are at present used as cross matching reagents. K4/I antibody will therefore be a useful routine reagent in cross matching laboratories, and, unlike the polyclonal antisera, will give an infinite suppiy of standardised reagent.
The use of K4/I antibody as an in vivo agentforthe prevention of rhesus disease of the newborn will be developed, and it is hoped that its use will make it unnecessary to continue the programme for immunisation of male volunteers which may prove hazardous to the immunised individuals. This programme has been necessary since the successful prevention ofthe disease has drastically reduced the number of donors with useful antibodies produced during pregnancy.
CLAIMSFiledon15Sept1983 1. A method for preparing a monoclonal cell line capable of producing a human monoclonal antibody against Rhesus D antigen, characterised in that anti-D producing B cells are infected with EB virus and said B cells are then cultured and cloned.
2. An EB virus-transformed human monoclonal cell line characterised in that it produces a human monoclonal antibody against Rhesus D-antigen.
3. A human monoclonal antibody ofthe lgG class with klight chains characterised in that said human monoclonal antibody is directed againstthe Rhesus
D antigen on human rhesus positive red blood cell membranes.
4. A human monoclonal antibody as claimed in claim 3, characterised in that said antibody agglutinates D positive red blood cells at a titre of 1:256 in indirect antiglobulin tests.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (4)
1. A method for preparing a monoclonal cell line capable of producing a human monoclonal antibody against Rhesus D antigen, characterised in that anti-D producing B cells are infected with EB virus and said B cells are then cultured and cloned.
2. An EB virus-transformed human monoclonal cell line characterised in that it produces a human monoclonal antibody against Rhesus D-antigen.
3. A human monoclonal antibody ofthe lgG class with klight chains characterised in that said human monoclonal antibody is directed againstthe Rhesus
D antigen on human rhesus positive red blood cell membranes.
4. A human monoclonal antibody as claimed in claim 3, characterised in that said antibody agglutinates D positive red blood cells at a titre of 1:256 in indirect antiglobulin tests.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08226513A GB2127434A (en) | 1982-09-17 | 1982-09-17 | A human monoclonal antibody against Rhesus D antigen |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08226513A GB2127434A (en) | 1982-09-17 | 1982-09-17 | A human monoclonal antibody against Rhesus D antigen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2127434A true GB2127434A (en) | 1984-04-11 |
Family
ID=10532973
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08226513A Withdrawn GB2127434A (en) | 1982-09-17 | 1982-09-17 | A human monoclonal antibody against Rhesus D antigen |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2127434A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0115476A2 (en) * | 1983-01-21 | 1984-08-08 | MonoCarb AB | Monoclonal antibody formulation for diagnostic use |
| EP0115062A2 (en) * | 1982-12-30 | 1984-08-08 | Biotest Aktiengesellschaft | Monoclonal antibody specific for human blood group antigen D (Rh0), and reactive in a direct agglutination test, and hybridoma cell lines procuding these monoclonal antibodies |
| WO1986000927A1 (en) * | 1984-07-31 | 1986-02-13 | Axon Healthcare Ltd. | Antibody production |
| GB2189506A (en) * | 1986-04-25 | 1987-10-28 | Central Blood Lab Authority | Human anti-rhesus d producing heterohybridomas |
| EP0249557A1 (en) * | 1986-06-12 | 1987-12-16 | Fondation Centre National De Transfusion Sanguine | Culture medium containing human albumin, method of preparing an injectable product from this medium, product obtained and its use, composition obtained |
| WO1996028473A1 (en) * | 1995-03-16 | 1996-09-19 | Medenica, Rajko, D. | Human monoclonal antibody against lung carcinoma |
| US5665356A (en) * | 1987-09-18 | 1997-09-09 | The National Blood Authority | Human anti-Rh (D) monoclonal antibodies |
| US7399471B2 (en) | 1996-06-24 | 2008-07-15 | Zlb Behring Ag | 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1982003089A1 (en) * | 1981-03-06 | 1982-09-16 | Lennox Edwin Samuel | Monoclonal antibody |
| GB2097425A (en) * | 1981-03-06 | 1982-11-03 | Celltech Ltd | Monoclonal antibody for B type blood cells |
-
1982
- 1982-09-17 GB GB08226513A patent/GB2127434A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1982003089A1 (en) * | 1981-03-06 | 1982-09-16 | Lennox Edwin Samuel | Monoclonal antibody |
| GB2097425A (en) * | 1981-03-06 | 1982-11-03 | Celltech Ltd | Monoclonal antibody for B type blood cells |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0115062A2 (en) * | 1982-12-30 | 1984-08-08 | Biotest Aktiengesellschaft | Monoclonal antibody specific for human blood group antigen D (Rh0), and reactive in a direct agglutination test, and hybridoma cell lines procuding these monoclonal antibodies |
| EP0115062A3 (en) * | 1982-12-30 | 1986-08-27 | Biotest Aktiengesellschaft | Monoclonal antibody specific for human blood group antigen d (rh0), and reactive in a direct agglutination test, and hybridoma cell lines procuding these monoclonal antibodies |
| EP0115476A2 (en) * | 1983-01-21 | 1984-08-08 | MonoCarb AB | Monoclonal antibody formulation for diagnostic use |
| EP0115476A3 (en) * | 1983-01-21 | 1988-10-12 | Monocarb Ab | Monoclonal antibody formulation for diagnostic use |
| WO1986000927A1 (en) * | 1984-07-31 | 1986-02-13 | Axon Healthcare Ltd. | Antibody production |
| FR2601963A1 (en) * | 1986-04-25 | 1988-01-29 | Central Blood Lab Authority | HETEROHYBRIDOMES PRODUCING HUMAN ANTI-RHESUS MONOCLONAL ANTIBODIES |
| EP0251440A2 (en) * | 1986-04-25 | 1988-01-07 | Central Blood Laboratories Authority | Human anti-Rhesus D producing heterohybridomas |
| GB2189506A (en) * | 1986-04-25 | 1987-10-28 | Central Blood Lab Authority | Human anti-rhesus d producing heterohybridomas |
| EP0251440A3 (en) * | 1986-04-25 | 1989-07-26 | Central Blood Laboratories Authority | Human anti-rhesus d producing heterohybridomas |
| BE1001517A5 (en) * | 1986-04-25 | 1989-11-21 | Central Blood Lab Authority | Heterohybridomas PRODUCING MONOCLONAL ANTI-HUMAN RHESUS D. |
| GB2189506B (en) * | 1986-04-25 | 1990-08-08 | Central Blood Lab Authority | Human anti-rhesus d producing heterohybridomas |
| FR2600076A1 (en) * | 1986-06-12 | 1987-12-18 | Fond Ctre Nal Transfusion | CULTURE MEDIUM COMPRISING HUMAN ALBUMIN, PROCESS FOR PREPARING A PRODUCT INJECTABLE THEREFROM, PRODUCT OBTAINED AND USE THEREOF, COMPOSITION OBTAINED |
| EP0249557A1 (en) * | 1986-06-12 | 1987-12-16 | Fondation Centre National De Transfusion Sanguine | Culture medium containing human albumin, method of preparing an injectable product from this medium, product obtained and its use, composition obtained |
| US5021349A (en) * | 1986-06-12 | 1991-06-04 | Foundation Centre National de Transfusion Sanguine | Culture medium containing human albumin, process for the preparation of an injectable product from this medium, product obtained and its use, and composition obtained |
| US5665356A (en) * | 1987-09-18 | 1997-09-09 | The National Blood Authority | Human anti-Rh (D) monoclonal antibodies |
| WO1996028473A1 (en) * | 1995-03-16 | 1996-09-19 | Medenica, Rajko, D. | Human monoclonal antibody against lung carcinoma |
| US7399471B2 (en) | 1996-06-24 | 2008-07-15 | Zlb Behring Ag | 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 |
| US7429647B2 (en) | 1996-06-24 | 2008-09-30 | Zlb Bioplasma Ag | 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 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |