Catalogue 2009/2010. Immunological and biochemical services

Transcription

1 Catalogue 2009/2010 Immunological and biochemical services 1

2 Customised Services Page Antisera and Polyclonal Antibodies 4 Guarantee offer - Rabbit antibodies with guaranteed quality 5 Inclusive offers Rabbit antisera 6 Rabbit antisera against peptides - Complete & Easy 7 Rabbit antisera against modified peptides 8 Single services (rabbit, goat, guinea pig, mouse, rat) 9 Standard immunisation protocols 10 Antigen Specifications 11 Monoclonal Antibodies 12 Guarantee offer Development of mouse monoclonal antibodies 13 Production of monoclonal antibodies in cell culture 14 Development of recombinant antibodies 15 Characterisation of monoclonal antibodies Affinity determination of monoclonal antibodies Modification of Antibodies 17 Hapten Synthesis and Modification 18 Peptide Synthesis and Modification 19 Synthesis of modified peptides 19 Standard peptide synthesis 20 Development, Validation and Production of Immunoassays 21 HCP-specific ELISA for quality control 23 Appendix General and additional conditions of sales Prices are valid from 1 April All prices are subject of change without notice prior to confirmation of an order. 2

3 BioGenes your partner for immunological and biochemical services BioGenes has been successfully engaged in business for more than 16 years as an outsourcing partner and service provider for the pharmaceutical and biotechnology industry as well as for research institutes world wide. Our certified company offers immunological and biochemical services for different fields of R&D, validation, production and quality control of new therapeutic substances and diagnostics. Our qualified scientists develop solutions for single scientific endeavours as well as for complete projects, strictly confidential and in close collaboration with the customer. BioGenes primary aims are to satisfy customer s requirements and to offer flexibility and extensive scientific support. BioGenes has been certified since 1999 according to DIN EN ISO BioGenes is licensed to manufacture immunoassays (antigens/antibodies) in accordance with the German Medicines Act (Deutsches Arzneimittelgesetz). BioGenes collaborates with other small and medium-sized biotechnology companies within the SciTrix network ( The services of these companies complement the service profile of BioGenes. Complex outsourcing-projects for pharmaceutical research and development can thus be realised by a one-shop service provider. The services of these companies include: - Proteome analysis and protein identification - Peptide synthesis - Development and production of recombinant proteins - Production of monoclonal antibodies in gram scale - Bioanalytics (GLP), pharmacokinetics All services presented in this catalogue are suggestions and can be tailored to the needs of the customer. We look forward to a successful collaboration. 3

4 Polyclonal Antibodies BioGenes offers customised production of polyclonal antisera and antibodies in rabbit, goat, mouse, guinea pig and rat against all different kinds of antigens, e.g. proteins, peptides, haptens and toxins. All animals are supplied by authorised animal farms, are housed and handled according to legal guidelines and are permanently monitored. Our services include qualified scientific consulting including assistance in antigen design and selection of suitable peptides. The customers can use the BioGenes standard immunisation protocol or follow their own immunisation scheme. Rabbits and goats will be kept after finalisation of the immunisation procedure. Final bleeding will be performed in agreement with the customer and is free of charge. Final bleed of goats is not permitted. BioGenes provides different standard offers and also individual solutions according to individual requirements. All antisera are tested by ELISA (internal control) provided that suitable antigen is available. All inclusive offers for peptide antisera (excluding guarantee offers) include ELISA titre determination as an additional service (without detailed protocol). The following additional services can be provided: - Affinity chromatographic isolation of antibodies from antiserum - Semiquantitative testing of antisera and antibodies by ELISA - Labelling of antibodies - Preparation of antibody columns If you have any additional requirements or questions, please do not hesitate to contact us for further assistance and specific offer proposals. 4

5 Polyclonal Antibodies Guarantee offers Rabbit antisera BioGenes guarantees antisera with a minimum titre against your antigen! We offer the following services: Guarantee offer 1 Protein antigen (1.5 mg protein in solution is required) - Testing of antigen for quantity and purity (recommended: > 90%) - Testing of pre-immune sera and selection of suitable animals - Immunisation of 2 rabbits according to BioGenes immunisation protocol until the guaranteed minimum titre of 1:20,000 (max. 3 months) is attained - Determination of antibody titre - Delivery of pre-immune sera and 100 ml antiserum with the guaranteed titre - Documentation including titre protocol Price for the complete service: Guarantee offer 2 Peptide antigen - Peptide synthesis (15 aa, mg, purity 80%), conjugation to a carrier protein - Testing of pre-immune sera and selection of suitable animals - Immunisation of 2 rabbits according to BioGenes immunisation protocol until the guaranteed minimum titre of 1:10,000 (max. 3 months) is attained in case of peptide length of aa and conjugation via terminal Cysteine - Determination of antibody titre - Delivery of pre-immune sera and 100 ml antiserum with the guaranteed titre - Documentation including titre protocol Price for the complete service: 1, The guarantee is fulfilled if the above quantities of antiserum are produced and the guaranteed titre is attained. The guarantee refers to the recognition of the respective antigen employed in the ELISA. If the guarantee can not be fulfilled, the only charge due is for peptide synthesis and conjugation. Rabbits will be kept until the customer has decided how to proceed. Costs for additional services such as isolation of IgG (total IgG or monospecific IgG) from antiserum will be calculated separately. 5

6 Polyclonal Antibodies Inclusive offers Rabbit antisera Antisera against protein Immunisation of 2 rabbits according to BioGenes standard immunisation protocol, delivery of 1.5 ml of pre-immune serum and 20 ml antiserum per rabbit Antisera against peptides Peptide synthesis (15 aa, mg, purity 80%) including assistance in sequence selection, conjugation with a carrier protein, immunisation of 2 rabbits according to BioGenes standard immunisation protocol, ELISA titre test, delivery of 1.5 ml of pre-immune serum and 20 ml antiserum per rabbit Antisera against a mixture of 2 peptides Peptide synthesis of 2 peptides (15 aa, mg, purity 80 %) including assistance in sequence selection, conjugation with a carrier protein, immunisation of 2 rabbits with a peptide mix according to BioGenes standard immunisation protocol, ELISA titre test, delivery of 1.5 ml of pre-immune serum and 20 ml antiserum per rabbit 1, The rabbits will be kept until the customer has decided how to proceed. The prices are valid only in case of standard peptide synthesis. In case of shorter or longer peptides, the price will change by ca per amino acid. Unused peptides will be returned to the customer at the end of the work. 6

7 Polyclonal Antibodies Rabbit antisera against peptides - Complete & Easy Price: 1, The following services are included: - Assistance in selection of a peptide as a suitable epitope - Peptide synthesis (12-16 amino acids, mg, purity 80 %, quality control by HPLC, MS) - Conjugation of 5 mg peptide to a carrier - Immunisation of two rabbits over 3 months (see protocol) - ELISA titre test of the first bleeding - Delivery of pre-immune sera, antisera and remaining peptide Immunisation protocol: 1 st day 1 st Immunisation and bleed of pre-immune serum (1.5 ml) 7 th day 2 nd Immunisation 14 th day 3 rd Immunisation 28 th day 4 th Immunisation 35 th day Bleed (20 ml per rabbit) 49 th day 5 th Immunisation 63 rd day Bleed (20 ml per rabbit) 77 th day 6 th Immunisation 91 st day Final bleed (approx. 50 ml per rabbit) 98 th day delivery of pre-immune sera, antisera and remaining peptide Please note: This protocol cannot be altered. 7

8 Polyclonal Antibodies Rabbit antisera against modified peptides Inclusive offer anti-phosphopeptide-specific antibodies Price: 2, The following services are included: - Synthesis of phosphopeptide (12 aa + one phosphorylation, mg, purity 80 %, quality control by HPLC and MS) - Synthesis of the corresponding, unphosphorylated peptide (12 aa, 5-10 mg, purity 80%, quality control by HPLC and MS) - Conjugation of phosphorylated peptide to a carrier protein - Immunisation of 2 rabbits over 42 days (see protocol) - Production of pre-immune serum and antiserum - ELISA titre test of antisera against coated phosphopeptide-conjugate (different carrier protein than for immunisation) - Affinity purification of up to 2x20 ml antiserum using the phosphorylated peptide followed by isolation using the unphosphorylated peptide, including production of specific columns - Delivery: specific anti-phosphopeptide antibodies, antibodies obtained by purification of antiserum using unphosphorylated peptide, test serum, and remaining peptides - Keeping of rabbits if required (with additional costs) - Optional: ELISA of phosphospecific antibodies (with additional costs) Immunisation protocol: 1 st day 1 st Immunisation and bleed of pre-immune serum (1.5 ml) 7 th day 2 nd Immunisation 14 th day 3 rd Immunisation 28 th day 4 th Immunisation 42 nd day 5 th Immunisation and bleed of antiserum (20 ml per rabbit) Customised antibodies against other modified peptides are available on request. 8

9 Polyclonal Antibodies Prices in for single services Services Rabbit Goat Immunisation and production of antiserum using BioGenes standard 1 rabbit immunisation protocol 2 rabbits Isolation total-igg (per antigen) * (up to 20 ml serum per lot) per animal * (up to 40 ml serum per lot) Preparation of affinity column (with CNBr-Sepharose) for isolation of monospecific IgG Isolation of monospecific IgG * (up to 20 ml serum per lot) * (40-50 ml serum per lot) Pre-immune serum per animal for pre-testing 20, rabbits 15,00 from 10 rabbits Animal keeping including boost per month/animal, 1,5 ml antiserum (if requested) - beginning 1 month after the 1st bleed Additional antiserum per ml Peptide conjugation with a carrier protein for up to 10 mg peptide ELISA titre test per antigen Services Mouse Guinea Pig Rat Immunisation and production of antiserum using BioGenes standard immunisation protocol - price per animal animal 150, animals 125,00 from 5 mice animal from 2 animals animal animals from 5 rats Isolation of total-igg on request 130,00 on request Preparation of affinity column (with CNBr-Sepharose) for isolation of monospecific IgG on request * on request Isolation of monospecific IgG * (up to 20 ml serum per lot) * ELISA titre test of antibodies is not included but can be ordered separately. on request 9

10 Polyclonal Antibodies Standard immunisation protocols Rabbit Protein Rabbit Peptide Goat Day 0 1 st Imm/1.5 ml Pre 1 st Imm/1.5 ml Pre 1 st Imm/5ml Pre Day 7 2 nd Imm 2 nd Imm 2 nd Imm Day 14 3 rd Imm 3 rd Imm 3 rd Imm Day 21 Day 28 4 th Imm/20ml Serum 4 th Imm 4 th Imm Day ml Serum 100 ml Serum Day 42 Day 49 Mouse Guinea Pig Rat Day 0 1 st Imm 1 st Imm/ ml Pre 1 st Imm/ ml Pre Day 7 Day 14 2 nd Imm 2 nd Imm Day 21 Day 28 2 nd Imm 3 rd Imm 3 rd Imm Day 35 3 rd Imm Day 42 4 th Imm ml Test ml Test Day ml Serum Final Day 56 4 th Imm 4 th Imm Day ml Serum Final ml Test Day 77 4 th Imm Day ml Serum Final Imm = Immunisation Pre = Taking of pre-immune serum Test = Taking of test serum Serum = Taking of antiserum Final = Final bleeding Final bleeding is free of charge. Final bleeding of goats is not applicable. The immunisation schedule can be changed for all species according to the customer s requirements. 10

11 Polyclonal Antibodies Antigen requirements Quantities per animal with reference to the standard immunisation protocol Rabbit Goat Peptide 2 mg 5 mg Protein in solution mg 2.5 mg Protein in SDS-PAGE 0.7 mg 2.5 mg Peptide conjugate 5 mg 7 mg Mouse Guinea Pig Rat Peptide 1 mg 1-2 mg 1-2 mg Protein in solution 0.5 mg 0.5 mg 0.5 mg Protein in SDS-PAGE Peptide conjugate 2 mg 2 mg 2 mg Antigen can be provided in any of the following forms: - lyophilised - dissolved or precipitated in buffer (concentration approx mg/ml) - in polyacrylamide gel (Coomassie-stained is possible; up to 500 µl gel can be used per injection) 11

12 Monoclonal Antibodies BioGenes has successfully generated monoclonal antibodies against different kinds of antigens including: - peptides, soluble proteins, membrane proteins, phosphorylated antigens, small organic molecules such as oligo- and polysaccharides as well as against substances highly toxic for animal cells such as Amanitine and Botulinum toxin. BioGenes professional expertise includes extensive experience in development of hybridomas for research and manufacturing purposes. BioGenes thus offers monoclonal antibodies with a guarantee for success. In the case of more complex projects, we will willingly provide special offers according to the customer s requirements and specifications. These offers are module-based offers meaning that each work phase will be invoiced separately. According to the customer s requirements, certain work phases can be added or deleted. We suggest that you discuss all details of the project with the experts of BioGenes (e.g. screening system, selection criteria and guarantee conditions) before starting the work. All work phases and results will be documented in detail. The customer will receive complete documentation. All results are the property of the customer after finalisation of the project. BioGenes is not entitled to either use the results or to exploit the outcome of the project and will not provide the results for use by third parties unless otherwise agreed in writing with the customer. The project is treated as strictly confidential. BioGenes has the experience and capacity to realise an extraordinarily large number of orders. This means that the customer has the opportunity to establish antibody libraries. In addition, BioGenes offers the development of recombinant antibodies and further services for antibody characterisation in close co-operation with a partner. Please contact us. We will be delighted to provide consultation regarding your individual requirements and to offer you specific proposals. 12

13 Monoclonal Antibodies Antibodies with guarantee Full guarantee without limitation of positive clones At least 3 positive stable clones will be guaranteed Price: 8, Duration of project: 3 to 4 months after receipt of an antigen Quantity: 3 cryo cultures and 10 ml of cell culture supernatant from each stable hybridoma cell line Development of hybridoma cell lines includes the following work phases: 1. Immunisation, cell fusion, selection and screening The work phase contains: Immunisation of up to 10 mice, cultivation of the necessary myeloma cell line, determination of titre in antiserum, cell fusion, including selection by means of HAT medium and screening. 2. First clonings This work phase contains first clonings including screenings. Positive clones will be cultivated and tested several times according to selected criteria. The customer receives 1ml of supernatant of each positive clone for testing in his own system. 3. Final cloning and cryo cultures This work phase contains all preparatory steps to obtain pure clones (second cloning and screening). The sufficient time frame of cultivation ensures that the clones will be stable. Three cryo cultures will be prepared for each positive stable clone. The cryo cultures and 10ml of cell culture supernatant of each clone will be delivered to the customer. Furthermore, additional cryo cultures can be prepared upon request of the client. These cultures will neither be used by BioGenes nor by any third party. 4. Characterisation of selected clones Determination of the Ig subclass and mycoplasma testing. Documentation: The customer receives complete documentation of all working steps. BioGenes guarantees that at least three IgG producing positive clones against the used immunogen can be delivered. The positive reaction of IgG refers to the test system used by BioGenes (ELISA). At the end of the development, the customer will receive all clones and the above-mentioned reports. 13

14 Monoclonal Antibodies Production of monoclonal antibodies in cell culture Production of monoclonal antibodies in cell culture will be carried out with hybridoma cells specifically generated by BioGenes according to the customer s specification or with those provided by the customer. In case of delivery of clones by the customer: BioGenes requires the clone as a cryo culture with data about the medium, growth conditions and a certificate of analysis indicating a negative mycoplasma test. If the customer does not have such a certificate, then the cultures can be tested by a partner of BioGenes. In such a case, two cryo cultures from one batch (one for testing and one for production) are necessary. Based on a starting production rate of mg/l cell culture supernatant, the following prices apply per antibody (purified by Protein A) Antibody lot [mg] Price in , , Any necessary reclonings will be carried out in agreement with the customer and will be additionally invoiced. For production of larger quantities, the price will be provided on request. Long-term storage and maintenance of clones (cryo cultures) can be provided. Please request a specific quotation. 14

15 Modification of Antibodies BioGenes modifies polyclonal and monoclonal antibodies according to your requirements. The service includes: Conjugation of antibodies with enzymes (peroxidase, alkaline phosphatase) Labelling of antibodies with fluorescent markers (FITC, TRITC, Texas red, phyco erythrine etc.) Labelling of antibodies with biotin and derivatives Gold labelling of antibodies; production of colloid conjugates with defined colloid sizes Coating of a carrier with antibodies (chromatographic carrier, plates, tubes etc.) Fragmentation of antibodies Moreover, we will comply with your needs and special requirements. Price Examples Labelling of 1-5 mg antibody with FITC Conjugation of 1-5 mg antibody with Peroxidase (POD) Biotinylation of 1-5 mg antibody Quality control of conjugates is not included but can be ordered separately. Prices for modification of larger antibody quantities, conjugation with other markers or proteins and the production of affinity chromatographic carriers will be given on request. 15

16 Hapten Synthesis and Modification BioGenes has long-standing and comprehensive experience in the fields of the chemistry and biochemistry of hapten conjugation and development of antibodies and immunoassays against haptens. We offer the following: Selection of suitable leading structures for antigen preparation Hapten synthesis on request Hapten modification and hapten derivation Individual concepts for directed conjugation and its optimisation Conjugation of haptens with LPH, KLH, BSA, ovalbumin or other carriers Conjugation of organic molecules with enzymes tracer development Analysis by means of HPLC, MS and NMR Development and production of competitive immunoassays Please let us know about your special aims and requirements. We can offer you an individual project proposal after consulting with you. 16

17 Peptide Synthesis and Modification BioGenes offers standard synthesis and also special synthesis in different quantities and purities: - Synthesis using rare components, for instance: D-amino acid, N-methylamino acid, hydroxyproline, phosphorylated amino acids (Tyr, Thr, Ser) - Multiple antigenic peptide (MAP) synthesis on the basis of PEG-resins. These MAP peptides can be used directly for immunisation without further conjugation to a carrier. - N-terminal modification of peptides: acetylation, palmitylation, conjugation with fluorescent markers, biotinylation, prolongation with spacer molecules (Ahx or β-ala), insertion of special groups for 125-Iodine labelling or linker groups for selective conjugation of peptides to carrier proteins. Please inform us about your special requirements. We will be pleased to discuss them with you and provide an individual offer. Peptide synthesis is performed by Biosyntan Berlin. 17

18 Standard peptide synthesis Prices in HPLC-purity 80% HPLC-purity 95% Quantity 2mg 5mg 10mg 15mg 20 mg 2mg 5mg 10mg Amino acid All peptides are subject to quality control by mass spectrometry and HPLC and will be delivered in lyophilised form as a TFA salt. Delivery time: 80% purified peptides, ca. 10 days 95% purified peptides, ca. 2-3 weeks Prices and delivery times for peptide synthesis are valid for normal amounts. Prices for other quantities, longer peptides and special synthesis are available on request. 18

19 Development, Validation and Production of Immunoassays BioGenes offers the development of immunoassays for qualitative and quantitative determination of antigens according to the customer s requirement. The immunoassays are designed on the basis of micro titre plates or tubes as: competitive assay for determination of haptens sandwich-assay for determination of proteins The development will be carried out in close consultation between the customer and BioGenes with regard to the project at hand. The customer is entitled to actively engage at every stage of the development or to change, supplement of cancel working packages. Invoicing of the project will be carried out according to the work packages. The customer will receive a detailed report on each working package at the end of the project. The development of immunoassays involves in principle the following work phases: 1. Preparation of immunogen Modification and conjugation of haptens (chemical synthesis of some suitable hapten derivatives, conjugation of modified haptens to carrier proteins, analytical characterisation of the products) Synthesis and conjugation of peptides Purification and modification of proteins 2. Production of antibodies Immunisation of animals (species according to customer s requirements) with all prepared antigens and isolation, purification and characterisation of polyclonal or monoclonal antibodies Determination of cross reactivity, specificity and avidity of antibodies 3. Development of tracer Conjugation of antibodies or haptens with different markers (enzymes or dyes) 19

20 4. Development of assay Optimising of procedures for carrier coating using antibodies or antigens Optimising of procedures for antigen determination Determination of analytical assay parameters Investigations concerning stability of detailed components of assay, optimisation of production 5. Validation of assay Determination of statistical assay parameters Evaluation and optimisation according to the customer s requirements 6. Production of assays Production of assays in agreed quality and quantity Delivery of all components in the necessary quantity to ensure continuous production Permanent quality control of all components Moreover, BioGenes has extensive experience and is able to offer consultation services in case of single research projects as well as complete projects in accordance with international guidelines. Please contact us. We can provide specific proposals in accordance with your requirements. 20

21 Complete Project - Customised Host Cell Protein (HCP) - ELISA for Quality Control Contaminating host cell proteins (HCP) are of special relevance in biotechnological manufacturing processes. Consequently, regulatory authorities demand HCP testing for the approval of each batch of biopharmaceuticals. For each biopharmaceutical product, individual antibodies and test systems for HCP determination need to be developed. Developing a customised HCP assay for quantitative determination of process-specific contaminants can be ordered as a project on its own or as part of a project: Phase I: Characterisation of antigen Phase II: Development and testing of polyclonal antisera - Immunisation of goats or rabbits and testing of polyclonal antisera by: - ELISA for titre determination - Western blot using antiserum of each animal on antigen HCP mix Phase III: ELISA development in buffer matrix - Affinity purification of antisera - Production of enzyme conjugates for ELISA development and validation - Development of a HCP standard - Optimisation of all relevant parameters of the ELISA Phase IV: Adaptation to production matrix - Testing of matrix effects - Adaptation of the ELISA to production matrix Phase V: Validation of the developed ELISA - Precision - Accuracy - Specificity - Standard curve - Test range limit and limit of detection Phase VI: Production of ELISA Additional services include stability tests and further performance tests according to the customer s requirements. The documentation provided is based on regulatory guidelines. 21

22 Please note! All products listed in this catalogue are for laboratory use only. They are not medicines or antibodies/antisera for test purposes as defined by pharmaceutical law and they must not be used for this purpose except when stated! Proteins and glycoproteins are isolated from human serum or plasma which is tested for HIV and hepatitis viruses. Please use these products with care because no assay fully ensures purity from contamination. Sera and antibodies are produced with animals known to be free from disease contagious for humans or animals. Nevertheless, the animal sera should be treated as potential infectious material. Please ensure that waste and packaging materials are sterilised. Sera and antibody solutions are stabilised with 0.02 % Thimerosal. Any other products used for stabilising are stated. Unless otherwise specified, all products should be stored at 0 C - 4 C. Solutions may contain sodium azide (NaN 3 ) that can develop toxic and explosive gases under the influence of acids. Solutions containing sodium azide or Thimerosal are toxic! Abbreviations aa Ahx BSA ELISA FITC HPLC IgG KLH LPH MS NMR TFA TRITC Amino acid Aminohexanoic acid Bovine serum albumin Enzyme-Linked Immunosorbent Assay Fluorescein isothiocyanate High pressure liquid chromatography Immunglobuline G Keyhole limpet hemocyanine Limulus polyphemus hemocyanine Mass spectrometry Nuclear magnetic resonance Trifluoroacetic acid Tetramethylrhodamine B isothiocyanate 22

23 General Sales Conditions State as of February The following conditions apply to all sales and deliveries insofar as other conditions have not been agreed upon in writing. The business conditions of the customer are only applicable insofar as BioGenes has given its approval in this respect. 2. The offers are based on availability. Contracts only arise as a result of confirmation of order or delivery. We reserve the right to make slight alterations regarding package sizes, properties and quality. Delivery times are only approximate insofar as they have not been otherwise designated as binding in writing. 3. Those packages listed in the respective price lists can be delivered. Special sizes and their delivery conditions must be agreed upon in writing. BioGenes is entitled to make partial deliveries. A separate invoice can be issued for every partial delivery. 4. We are absolved from our duty to deliver in case of force majeure, disruptions in operation, strikes or other disorders beyond the control of BioGenes or their suppliers for the duration of the disruption or its effects. 5. Shipment or dispatch is made at the discretion of BioGenes. Deliveries are dispatched from Berlin. Additional costs due to special dispatch requirements of the customer are charged to the customer. 6. The risk is borne by the customer as soon as the wares have been handed over to the transportation company. 7. The prices include packaging costs, however, statutory value added tax (VAT) is not included in the prices. Dispatch costs are charged to the customer insofar as other stipulations have not been made in writing. If BioGenes generally raises or lowers prices after a period of four months after the order has been made or after confirmation of the order, then that price applies which is valid on the day of delivery. The publication of this catalogue replaces and invalidates all previous price lists. 8. Invoices are payable net within 30 days from the day of issue insofar as it has not been otherwise agreed in writing. Payment is regarded as having been made when the funds are at the disposal of BioGenes with a bank. Discount, expenses and bank charges are payable by the customer. In case of late payment, BioGenes without sending a reminder calculates interest due at a rate of 5% above the discount rate of the Federal German Central Bank. BioGenes is entitled at any time to demand security provision by the customer. The customer may only contest the claims of BioGenes with undisputed or legally binding counterclaims. The customer, in particular, is not entitled to withhold or to reduce the payment of the invoice amounts due as a result of complaints about the wares. 9. The delivered wares remain the property of BioGenes until the customer has paid all demands resulting from the business relationship. The proviso wares may not be pawned, pledged nor provided as security. Insofar as the customer sells the proviso wares, he is required to relinquish his claims resulting from the sale in favour of BioGenes beforehand. If BioGenes considers its claims endangered, the customer is required to ensure the return of the proviso wares on demand or that he informs the purchasers about relinquishing his claims and to return all necessary documents. The return of the proviso wares does not constitute cancellation of the contract. 10. BioGenes guarantees a constant high quality of its products. Deficiencies in the delivered wares or false deliveries are to be notified in writing eight days after receipt of the wares at the latest and, in the case of hidden deficiencies, immediately after their discovery. If this deadline is exceeded or if the wares are inappropriately stored, handled or processed, all deficiency claims are void. The right to recourse expires six months after receipt of the wares in every case. In case of justified complaints, missing amounts are delivered or the wares taken back, exchanged or the customer granted an appropriate price reduction at the discretion of BioGenes. If a replacement delivery also shows deficiencies, the customer is entitled to return the wares or to demand a price reduction. 11. The products delivered by BioGenes are for laboratory use only. The delivered wares may not be used for human or veterinary medicine, in the food and consumables industry, cosmetics etc. which involve a direct or indirect administration of these products to man or animal insofar as this is not clearly indicated in written form. 12. BioGenes is only liable for properties assured in writing. Liability claims are only justified when damage is deliberately caused or due to gross negligence by BioGenes or its helpers or where essential contract duties have been violated. The liability of BioGenes is limited to the predictable damage resulting from this error. Liability claims are otherwise excluded. BioGenes is not liable for damage arising from inappropriate use or storage of its products. 13. BioGenes does not accept the liability for delivered materials by the customer (antigens, antibodies, peptides, proteins and chemical reagents). BioGenes is also not responsible for materials which are ordered for the customer by another supplier. 14. BioGenes has the right to decide about the usage of the suitable scientific and technical methods for processing of the materials to realise the customer requirements, unless there is another agreement in writing. 15. The legal jurisdiction for deliveries and payment is Berlin, Germany. German law applies. 23

24 Additional Conditions for Customer-Specific Services The general sales and delivery conditions of BioGenes GmbH apply. Furthermore, the following apply: 1. The antibodies, antisera etc. and carriers coated with them, with the exception of chromatographic media, are the property of the customer after fulfilment of the contract. No information is provided to third parties regarding their nature, composition and use. The use of these products by BioGenes can only result with the expressed permission of the customer. The antigens provided remain the property of the customer in all cases. 2. The required products are delivered together with documentation by courier. This documentation includes an immunisation protocol in accordance with the service ordered and a product description. 3. The customer provides the necessary amount of the antigen after signing the contract or otherwise in accordance with another agreement made. If no consultation has been made regarding the carrier in the case of delivery of peptides, BioGenes is entitled to use a carrier of its choice for conjugation. The customer must provide BioGenes with information on the order form regarding concentration of the antigen, buffer, stabilisers etc. Infectious antigens as well as antigens known to be hazardous to man and animal are not accepted. 4. Immunisation is performed in accordance with the BioGenes protocol. This protocol can be adapted to the wishes of the customer after consultation. All antisera are tested for reaction with the respective antigen for quality control purposes. It must be expressly pointed out that no liability is accepted for the ability of a peptide antibody to be used for protein determinations. The customer bears the risk regarding the peptide sequence selected. 5. If it is agreed to purify the polyclonal antisera then, if not otherwise specified, the total amount of antiserum is purified. In this case, only the specified purified product is delivered as well as a sample of the antiserum after consultation with the customer. If affinity chromatographic purification is agreed upon, then the carrier material of our own manufacture is only kept at the expressed wish of the customer. The carrier remains the property of BioGenes. 6. The experiments are performed by experienced specialists with extreme care and in accordance with legal requirements. If experimental animals are injured during the performance of the experiment without providing the agreed amount of antibody or antiserum or if the results of previous experiments are not reproducible, then the risk is borne by the customer. 24