Afuco platform for adcc enhanced therapeutic antibody development

Afuco™ Platform
Afuco™ Platform
USA
SUITE 203, 17 Ramsey Road Shirley, NY 11967, USA
Tel: 1-631-357-2254 Fax: 1-631-207-8356
info@creative-biolabs.com
UK
167-169 Great Portland Street, 5th Floor, London, W1W 5PE
Tel: 44-207-097-1828
Power For Next‐Generation ADCC+
Therapeutic Antibodies
HTTPS://ADCC.CREATIVE-BIOLABS.COM/

Afuco™ Platform
Table of Content
1. INTRODUCTION................................................................................................................................................................................. 3
2. OUR AFUCO™ PLATFORM.............................................................................................................................................................. 4
2.1 Fut8-/-
CHO-K1 Stable Cell Line Establishment......................................................................................................................................4
2.1.1 Project Overview ....................................................................................................................................................................................4
2.1.2 Methods & Results .................................................................................................................................................................................4
2.2 Antibody Preparation and Transfection ...................................................................................................................................................9
2.2.1 Antibody Preparation..............................................................................................................................................................................9
2.2.2 Fut8-/- CHO-K1 Cell Suspension Acclimation ........................................................................................................................................9
2.2.3 Antibody Transfection and Expression ...................................................................................................................................................9
2.2.4 Antibody Quality Control.......................................................................................................................................................................10
2.3 Antibody Fucose Analysis........................................................................................................................................................................10
2.3.1 Lectin Blot ............................................................................................................................................................................................10
2.3.2 Lectin ELISA ........................................................................................................................................................................................11
2.3.2 HPAEC-PAD Glycoform Analysis.........................................................................................................................................................12
3. OUR SERVICES ............................................................................................................................................................................... 12
3.1 Therapeutic ADCC⁺ Biobetter Antibody Production ............................................................................................................................12
3.2 Cell Line Development .............................................................................................................................................................................13
3.3 ADCC Analysis..........................................................................................................................................................................................13
Afuco™ Platform
USA
SUITE 203, 17 Ramsey Road
Shirley, NY 11967, USA
Tel: 1-631-357-2254 Fax: 631-207-8356
UK
167-169 Great Portland Street, 5th Floor, London, W1W 5PE
Tel: 44-207-097-1828
Power For Next‐Generation ADCC+
Therapeutic Antibodies
HTTPS://ADCC.CREATIVE-BIOLABS.COM/

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1-631-357-2254 | info@creative-biolabs.com | CREATIVE BIOLABS INC
Afuco™ Platform
1. Introduction
Treatment of cancer with therapeutic antibodies
Recombinant therapeutic antibodies represent a successful new class of drugs developed over the past two decades. Researchers are able to
design antibodies that specifically target a certain antigen, such as the one found on cancer cells before then multiplying said antibody in the lab.
The result are monoclonal antibodies that are used to treat many diseases, including some types of cancer.
One mechanism of action of antibody-based immunotherapy is the activation of immune effector cells to mediate antibody-dependent cell-
mediated cytotoxicity (ADCC). Thus, ADCC enhancement is important to push the efficacy of cancer antibodies as the artificially decreased
fucose content that leads to ADCC also results in an elevated killing activity against tumorigenic and infected cells, making them more powerful
and efficient.
So it is hardly surprising that the popularity of ADCC enhanced antibodies to be utilized in the development of next-generation therapeutic
antibodies is constantly growing. Creative Biolabs provides a comprehensive list of therapeutic antibodies with enhanced antibody-dependent
cellular cytotoxicity to accelerate your research process.
Fig.1 Moa of ADCC.
The benefits of ADCC enhanced antibodies
ADCC enhanced antibodies, also known as afucosylated antibodies, are artificially cultivated monoclonal antibodies engineered to exhibit a
decreased fucose content that in turn leads to higher ADCC. ADCC forms part of the humoral immune response to limit and contain infection and
has recently been identified as one of the critical mechanisms underlying the clinical efficacy of therapeutic antibodies, especially anticancer
antibodies.
Therapeutic antibodies fully lacking the core fucose of the Fc oligosaccharides have been found to exhibit much higher ADCC in humans than
their fucosylated counterparts.
But why are ADCC enhanced antibodies seeing such a steady rise in popularity? Well, they exhibit a number of significant benefits, the three
major ones being:
 enhanced ADCC activity
 improved FcγIIIa binding properties –
 quick and easy cultivation with a profitable yield
Thanks to these beneficial properties, they can be used in a number of medications and treatments targeting autoimmune diseases, cancer and
viral diseases such as COVID-19.
In the particular case of ADCC enhanced antibodies, those binding properties are further amplified, resulting in an elevated killing activity
against tumorigenic and infected cells.
Afuco™ platform for ADCC enhancement from Creative Biolabs
The constantly growing demand is just one of the reasons why antibody production and design plays a crucial role in today’s life-science
industry, be it to increase activity as well as functionality, reduce immunogenicity or extend the half-life.
The scientists at Creative Biolabs are specializing in afucosylated antibodies for ADCC enhancement. One of the most recent additions to the

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Afuco™ Platform
company’s services is the Afuco™ platform, used for the generation of ADCC enhanced antibodies by means of transient expression in CHO
cells. By using homologous recombination technology, we obtained a fucosyltransferse-engineered stable CHO cell line, which produce
defucosylated monoclonal antibodies with enhanced affinity for FcγRIIIa and enhanced ADCC activity.
2. Our Afuco™ platform
2.1 Fut8-/-
CHO-K1 Stable Cell Line Establishment
2.1.1 Project Overview
 Objective
Establish the Fut8 knockout cell line using CHO-K1-GS-/- cells.
 Description
1) Design gRNA according to the Fut8 sequence (Gene ID: 100751648).
2) Construct the knockout vector.
3) Transfect CHO-K1-GS-/- cells
4) Screen for positive cell clones.
 Target Gene
Fut8 (ID: 100751648)
 Plasmid
pGK1.1 (Amp)
 Host Cells
CHO-K1-GS-/- cells
 Final Delivered Items
Item Description Size Storage
1 Fut8 knockout (-/-) cells 1 vial Liquid nitrogen
2.1.2 Methods & Results
Part I Preliminary test
1) Optimize electroporation condition
The electroporation condition has been optimized.
2) Test the minimal absolute lethal dose of Puro
The minimal absolute lethal dose of Puro has been tested.
3) Test the clonability of CHO-K1-GS-/- cells
The clonability of CHO-K1-GS-/- cells has been tested.
Part II Design gRNA & construct knockout vector
1) Design gRNA
Gene Name: Fut8
Species: Chinese Hamster
mRNA Refseq: XM_003501735
Sequences:
TTTGGTCTCAAAAACCAAAAAACTTAAATCTGTTGATTCCAGGTTCCCATATATTCTTGGATATGCCAATTACTTTTTCTGTAAGCAAG
TGTTTCATAAAACTTTTACTTAACTTTCATATTGACCTGTACTATTCAACATTCAGCTATGTTAAAGTATTTGTGAAGTGTTTTGAAATG
ATTTTATATTTTCTAAGGTGAGAATAAATGAGAAAATGTTTTAATATGTCTCCAGTGCCCCCATGACTAGGGATACTAATTGAGTACCA

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Afuco™ Platform
GTACATTATCAGTGTGCTCTCCACTTCTCCCCAGAGTCCATGTCAGACGCACTGACAAAGTGGGAACAGAAGCAGCCTTCCATCCC
ATTGAGGAATACATGGTACACGTTGAAGAACATTTTCAGCTTCTCGAACGCAGAATGAAAGTGGATAAAAAAAGAGTGTATCTGGCC
ACTGATGACCCTTCTTTGTTAAAGGAGGCAAAGACAAAGTAAGTTAGACCAACAAGTGGTTCTGTATGGGATTATCTCTTAGTTGAA
GAAAATCCTTAATTCTGGGAACTTGTGGTTCTTGTTGCTAACTAATAGGTTCCAAAATCAAAGACTACATGTGCAAATATTAATCTAAT
CAAGTCATACCTTACTAGCTGTATCTGATGCAAATTAAGAAGTCTAAAATGAATTAGACTGCTGATTTGTGTAGCATCACTAG
Blue highlighted sequence: target site 1
Green highlighted sequence: target site 2
Red highlighted sequence: PAM
Fut8-gRNA1: TCTCGAACGCAGAATGAAAGAGG
Fut8-gRNA2: TGATGACCCTTCTTTGTTAATGG
2) Construct the knockout vector
 Construct information
Fig 1. pGK1.1 vector map
Fig 2. pGK1.1 vector after BbsI digestion
 Add joint sequence in gRNA
To clone gRNA into the BbsI-linearized vector, the joint sequence is needed. A “CACC” was added into the 5’ of the sense strand and
Lane 1: undigested vector
Lane M: DNA marker
Lane 2-4: linearized vectors

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Afuco™ Platform
a “AAAC” was added into the 5’ of the antisense strand. Besides a starting with G in gRNA sequence is necessary.
 Synthesize two oligos as below.
Bak-gRNA1-Sense: CACCGTCTCGAACGCAGAATGAAAG
Bak-gRNA1-Antisense: AAACCTTTCATTCTGCGTTCGAGAC
Bak-gRNA2-Sense: CACCGTGATGACCCTTCTTTGTTAA
Bak-gRNA2-Antisense: AAACTTAACAAAGAAGGGTCATCAC
Sequences in blue: complementary to the BbsI - digested vector
Yellow highlighted sequence: G added artificially.
 Anneal the synthesized single strand oligos to form dsDNA. The annealing reaction is as follows:
 Subclone the annealed dsDNA into pGK1.1 vector. The ligation reaction is as follows:
3) Transform into G10 competent cells and screen for the positive clones
 Selection of positive clones by PCR
Perform PCR with VSP and Fut8-antisense primers, and the expected PCR products is about 100bp.
VSP primer (near U6 promoter): CATATGCTTACCGTAACTTGAAAG
Fut8-Antisense primer: Reverse complement sequence of the Fut8-gRNA target site
Fig 3. PCR verification of positive clones.
Sense Oligo (10 μM) 10 μl
Antisense Oligo (10 μM) 10 μl
ddH2O 16 μl
Annealing Buffer (10x) 4 μl
Total Volume 40 μl
linearized pGK1.1 vector 1 μl
Annealed dsDNA 1 μl
T4 DNA Ligase 0.5 μl
10xT4 DNA ligase Buffer 1 μl
ddH2O 6.5 μl
Total Volume 10 μl
Lane M: DNA marker
Lane 1-3: positive clones for Fut8-gRNA1
Lane 4-6: positive clones for Fut8-gRNA2

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Afuco™ Platform
 Quality control
We sent 1# clone and 2# clone for sequencing and the sequence was aligned against reference sequence (see below). Please see the
attached sequencing data (file: Sequencing Results of Knockout Vector) for more details.
Fig 4. Sequencing verification of positive clones
Part III CHO-K1-GS-/- cells electroporation and knockout cells screening
1) CHO-K1-GS-/- cells electroporation with optimal conditions obtianed from preliminary tests
2) Detect the knockout efficiency of gRNA1 and gRNA2 in pool cells
Electrotransfected two knockout vectors into CHO-K1-GS-/- cells respectively. A sequence analysis was conducted using primers
(Fut8-seqF and Fut8-seqR) after a Puro selection. The appearance of impurity peak near the target site usually shows the knockout
event.
The chromatogram shows a significant impurity peak indicating the knockout event induced by the two gRNAs. So we
electrotransfected two knockout vectors into CHO-K1-GS-/- cells respectively in the following experiment.
Please see the attached sequencing data (file: Sequencing Results of Pool Cells) for more details
Fig 5. Sequencing data of pool cells electrotransfected with Fut8-gRNA1 knockout vector
Fig 6. Sequencing data of pool cells electrotransfected with Fut8-gRNA2 knockout vector
3) Isolate cell clones and extract genomic DNA
4) PCR amplify the region flanking the target site

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Afuco™ Platform
TTTGGTCTCAAAAACCAAAAAACTTAAATCTGTTGATTCCAGGTTCCCATATATTCTTGGATATGCCAATTACTTTTTCTGTAAGCAA
GTGTTTCATAAAACTTTTACTTAACTTTCATATTGACCTGTACTATTCAACATTCAGCTATGTTAAAGTATTTGTGAAGTGTTTTGAAA
TGATTTTATATTTTCTAAGGTGAGAATAAATGAGAAAATGTTTTAATATGTCTCCAGTGCCCCCATGACTAGGGATACTAATTGAGTA
CCAGTACATTATCAGTGTGCTCTCCACTTCTCCCCAGAGTCCATGTCAGACGCACTGACAAAGTGGGAACAGAAGCAGCCTTCCA
TCCCATTGAGGAATACATGGTACACGTTGAAGAACATTTTCAGCTTCTCGAACGCAGAATGAAAGTGGATAAAAAAAGAGTGTATC
TGGCCACTGATGACCCTTCTTTGTTAAAGGAGGCAAAGACAAAGTAAGTTAGACCAACAAGTGGTTCTGTATGGGATTATCTCTTA
GTTGAAGAAAATCCTTAATTCTGGGAACTTGTGGTTCTTGTTGCTAACTAATAGGTTCCAAAATCAAAGACTACATGTGCAAATATTA
ATCTAATCAAGTCATACCTTACTAGCTGTATCTGATGCAAATTAAGAAGTCTAAAATGAATTAGACTGCTGATTTGTGTAGCATCACT
AG
Fut8-seqF: TTTAATATGTCTCCAGTGCC
Fut8-seqR: CAACAAGAACCACAAGTTCC
Bule highlighted sequence: target site 1
Green highlighted sequence: target site 2
Red highlighted sequence: PAM
Yellow highlighted sequence: the pair of primer for Fut8 amplification.
The size of expected PCR product should be around 340 bp using the above primer
5) Digest PCR products with our Cruiser™ Enzyme to select positive clones
Cruiser™ Enzyme can recognize the nicks resulted from the knocking out process and will therefore cut such PCR products into two
bands (Fig 7).
The expected PCR product is about 340bp and the digestion products are about 190bp and 150.
Fig 7. Digestion of PCR products with Cruiser™ Enzyme.
6) Verification by sequencing
 Direct sequencing of PCR product
Lane M: marker
Lane 1-3: Positive clone

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Afuco™ Platform
We choose one PCR product that can be digested by Cruiser™ Enzyme for sequencing. Please see the attached sequencing data
(file: Sequencing Results of PCR Product for 154# Clone) for more details. The sequence in shadow is the target site of Fut8-gRNA1.
Fig 8. The sequencing chromatogram of PCR product for 154# clone.
 TA cloning and sequencing
Sequencing Results of TA Cloning.
The sequence alignment showed that the selected clone (154#) is a homozygous knockout mutant with one strand deleting 11 bases
(GAACGCAGAAT) and another inserting 1 bases (A).
Another positive clone (76#) is also a homozygous knockout mutant with one strand deleting 8 bases (AGAATGAA) and another inserting
1 bases (A).
Sequence alignment:
Fig 9. Sequencing verification of TA cloning of 154# clone.
Fig 10. Sequencing verification of TA cloning 76 clone
2.2 Antibody Preparation and Transfection
2.2.1 Antibody Preparation
 Antibody information
Antibody Name Isotype Vector
20Y52 Human IgG1 kappa pcDNA3.4
2.2.2 Fut8-/- CHO-K1 Cell Suspension Acclimation
a. Resuscitate CHOK1-GS/Fut8-ko cell line (medium 1640+10% FBS). Cell viability rate is 96%;
b. Adherent culture, after two stable passages, start serum-free domestication;
c. Observe the cell confluence under a microscope to reach 70-80%, add trypsin digestion, slowly pipetting and mixing, count with a cell
counter, inoculate 0.5×106cells/ml into 30ml acclimatization medium, use 125ml shake flask to cultivate and cultivate Conditions 37°
C,
8%CO2, 125rpm;
d. Measure cell density and viability every 2-3 days, select passage or change fresh medium according to cell density each time;
e. Continuously culture for about 2-3 weeks, the cells can be stably expanded and passaged, and the cells can be frozen;
2.2.3 Antibody Transfection and Expression
f. Use the CHOK1-GS/Fut8-ko suspension cells in good condition for antibody transfection. Take a total of 2 tubes for electroporation

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Afuco™ Platform
(5*10^6/tube)
The electroporation system of Lonza4D cell nuclear transfer instrument:
Transfection
Cells 5*10^6
20Y52H-Linaer 5ug
20Y52L-Linaer 5ug
Total Plasmid 10ug
g. After electrical stimulation, inoculate the cells in medium 1 to 1*10^6/mL, 37°C, 8% CO2, 125rpm for 48h;
h. After 48 hours of electroporation, the cells were screened with 0.9mg/ml G418 and the medium was changed every 3-5 days;
i. Continue the screening for about 2 weeks, and the cell status returns to normal; the cells are enlarged and cultured and frozen. The cell
line is named:
20Y52-CHOK1-pool cell.
2.2.4 Antibody Quality Control
 SDS-PAGE result:
Fig.11 12% SDS-PAGE analysis profiles of purified
 HPLC result: purity>99%s
2.3 Antibody Fucose Analysis
2.3.1 Lectin Blot
Lane M: Protein Marker
Lane 1:20Y52-CHOK1,Non-Reducing (2ug)
Lane 2:20Y52-CHOK1,Reducing (2ug)

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Afuco™ Platform
 Samples
1)20Y52-2 (CHOK1-GS/Fut8-ko)
2)Mouse anti-human IgG (H+L) Antibody
3)Primary antibody: Aspergillus Oryzae Lectin (AOL)-Biotin Conjugate (Form: Liquid Conc.: 1 mg/mL, Cat. A2659 TCI)
4)Secondary antibody: SA-HRP
 SDS-PAGE gel electrophoresis: 80V constant voltage electrophoresis for 0.5h, 100V constant voltage electrophoresis for 1.6h;
 Transfer membrane: use 0.22um NC membrane, 100v constant pressure ice bath transfer membrane for 60 minutes;
 Blocking: Prepare 10% skimmed milk powder and block for 1 hour, rinse with PBST 3 times, 8min/time;
 Primary antibody incubation: Dilute the antibody AOL biotin conjugate with 5% skimmed milk powder according to 1:500, incubate the NC
membrane overnight, rinse with PBST 3 times, 8 min/time
 Incubation of chromogenic antibody: Dilute SA-HRP with PBST according to 1:3000, incubate NC membrane at room temperature for 1h,
rinse with PBST 3 times, 8min/time
 Imaging: According to the enhanced luminescent agent: stabilizer=1:1, the color solution is prepared, and the Tianneng imager is used for
imaging. The results are as follows:
2.3.2 Lectin ELISA
 Coating
Dilute the following samples respectively with 10, 5, 2.5, 1.25, 0.625, 0ug/ml, a total of 6 gradients, and coat them on a high adsorption
ELISA plate, overnight at 4°C, and wash the plate 3 times with PBST
 Blocking: 0.2% BSA, 300uL/hole, sealed at room temperature for 1h;
 Detection: AOL Biotin Conjugate
 Imaging: SA-HRP
The original data of OD450 are as follows:
<> 3 4 7 8 ug/ml
A 0.0067 0.0056 0.0059 0.0066 0
B 0.0239 0.0252 0.3105 0.2975 0.625
C 0.0198 0.0157 0.6305 0.7519 1.25
D 0.0329 0.0095 0.88 0.8511 2.5

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Afuco™ Platform
E 0.0097 0.0142 1.1691 1.2584 5
F 0.0538 0.0223 1.3867 1.4063 10
 Data Analysis
Coating Con. ug/ml 0 0.625 1.25 2.5 5 10
20Y52-CHOK1-Fut8/ko 0.006 0.025 0.018 0.021 0.012 0.038
Moue anti hIgG Antibody 0.006 0.304 0.691 0.866 1.214 1.397
2.3.2 HPAEC-PAD Glycoform Analysis
Summary of total monosaccharide composition of the sample. The weight percentage of the sample is 0.11110.004219% (meanSD).
ng
Sample
weight
GlcNAc Gal Glc Xyl Man NGNA Total Weight%
20Y52-
CHOk1
3525 0.01593 2.539 0.1722 0.09473 1.203 0.03080 4.056 0.1151
3525 0.01223 2.472 0.1703 0.09707 1.150 0.03121 3.933 0.1116
3525 0.01193 2.394 0.1682 0.09150 1.064 0.03195 3.762 0.1067
In summary, this antibody is glycosylated with GlcNAc, Gal, Glc, and Man residues, which is typical for CHO cells. A small amount of Xyl was
also found in this sample. Fuc was not detected. The total monosaccharide (amino sugar, neutral sugar, & NGNA) weight percentage of this
sample is 0.11110.004219% .
3. Our Services
3.1 Therapeutic ADCC⁺ Biobetter Antibody Production
After your projects move to ADCC optimization, let our experts show you how to accelerate the development and unleash your ADCC-enhanced
antibody to an even greater potential. By the help of our specialists and their expertise in antibody production, as well as the state-of-the-art
technology, we are committed to delivering our customers with the best antibody engineering service and ensuring every step during process
meets your requirements.

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Afuco™ Platform
Features:
3.2 Cell Line Development
Creative Biolabs provides mammalian cell lines for the production of recombinant therapeutic proteins, which could produce a large number of
consistent quality products to meet current regulatory requirements.
Glyco-engineering host cell lines
Based on our advanced technology, we offer our customers with afucosylated cell lines. Our optimal glycol-engineering host cell line has several
advantages: (i) excellent glycosylation ability; (ii) preventing the synthesis of unfavorable glycan structures (iii) possibility to produce optimized
glycoforms. These properties are highly desirable for the production of bio-better versions of therapeutic proteins, such as afucosylated mAbs.
Highlighted features
 Glycan engineered CHO cell lines provided by us have extraordinary productivity, stability under long-term production and good overall
quality.
 Screening is done to thousands of clones through multiple evaluation stages. Starting with a small initial screening, we use shake flasks and
micro bioreactors to identify high-volume clones and gradually, scale them up.
 Comprehensive product quality attributes are characterized including glycosylation profiles, charge variation, aggregation levels and protein
sequence variation.
3.3 ADCC Analysis
With the help of our proprietary and advanced ADCC platform technology, Creative Biolabs has developed a revolutionary ADCC analysis
method that is believed to address all problems associated with the traditional ADCC analysis. Even with novel cell lines, we are able to provide
a more optimized method to measure target cell death with varying levels of biological relevance and sensitivity, all of which have
unprecedented levels of performance and consistency.
ADCC assays
 Target cell lysis
 Effector cells activation
 Real-time monitoring
With decades of experience in the field of antibody development, Creative Biolabs is able to provide our clients with the flexibility to adapt to the
evolutionary changes in ADCC⁺ antibody development filed. For more details about our service, please do not hesitate to contact us.
Quality
Promising on supreme antibody
activity and purity, our scientists
use their expertise in antibody
expression and purification with
state-of-the-art analytical
techniques to meet the needs of
our clients.
Scale
Generating from our optimized protein
expression system, we refine and
create a stable cell line that has a high
protein yield. Tools used include but are
not limited to 96-well plates, shake flask
fermentation, large bioreactors to scale-
up purified proteins delivered from
mammalian expression hosts.
Customization
We have knowledge on end-to-end
service development, ranging from
DNA synthesis to protein production.
If you’re ready to do the work in your
lab, we're also happy to assist you on
customized project.

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Afuco™ Platform
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All CREATIVE BIOLABS products including polyclonal antibodies, monoclonal antibodies from all species, recombinant monoclonal antibodies, single-domain
antibodies, bi- or tri-specific antibodies, BiTEs, immunotoxins, therapeutic antibodies and proteins, antibody-like molecules, such as affibodies, scaffolds,
monobodies, etc., hybridoma cell lines, biosimilars, stable cell lines, CAR, ELISAs, lateral flows, compounds, compound libraries, and other kits and assays are
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Nothing herein shall be regarded as an express or implied transfer or license of a party’s Background IP. CREATIVE BIOLABS is the sole and exclusive owner of
all right, title and interest in and to all intellectual property claiming or covering CREATIVE BIOLABS technology.

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Afuco™ Platform
7. Confidentiality.
During performance of the Services and for three (3) years thereafter, CREATIVE BIOLABS will treat all Data as proprietary and confidential and will not disclose
the same to any person except its employees, consultants, and subcontractors to whom it is necessary to disclose the Data for purposes of providing the
Services. CREATIVE BIOLABS shall protect the Data by using the same degree of care as CREATIVE BIOLABS uses to protect its own confidential information,
but in any event no less than a reasonable degree of care. Notwithstanding any other provisions herein, CREATIVE BIOLABS shall have no liability or obligation
to Client for, nor be in any way restricted in, its disclosure or use of any Data which (a) is already known to CREATIVE BIOLABS without obligation of
confidentiality to Client; (b) is or becomes publicly known by any means other than wrongful act of CREATIVE BIOLABS; (c) is received from a third party without
such party’s breach of obligation of confidentiality to Client; (d) is disclosed pursuant to an enforceable order of a court or administrative agency; and/or (e) is
independently developed by or for CREATIVE BIOLABS. Client acknowledges that, notwithstanding anything to the contrary herein, CREATIVE BIOLABS shall be
free to disclose Data, provided that in so doing CREATIVE BIOLABS never attributes or otherwise associates any such data with Client.
8. Payments.
The Client shall pay CREATIVE BIOLABS according to CREATIVE BIOLABS invoice(s). CREATIVE BIOLABS shall invoice the client following payment
schedules described in the quotation. The payment terms is 30 days, otherwise differently requested in the invoice. All payments due hereunder shall be made in
the currency specified by CREATIVE BIOLABS in writing. If Client defaults in any payment when due, CREATIVE BIOLABS, at its option and without prejudice to
its other lawful remedies, may delay performance, defer delivery, charge interest on undisputed amounts owed, and/or terminate the Services Agreement. If
payment is not received by the due date, a service charge will be added at the rate of 1.5% per month (18% per year) or the maximum legal rate, whichever is
less, to unpaid invoices from the due date hereof. If CREATIVE BIOLABS is compelled to bring suit to collect amounts due hereunder, it shall also be entitled to
recover interest on amounts due as provided by law and reasonable attorney fees and costs of suit incurred in connection with the action. Client’s acceptance of
delivery of any Service based on this Service Agreement shall constitute a representation that Client is solvent.
9. Indemnity.
The Client shall defend and indemnify CREATIVE BIOLABS and its affiliates, directors, officers,employees, representatives, consultants, agents and service
providers (collectively, the "Company Indemnified Parties"), against any and all costs, damages, expenses (including reasonable legal fees) and losses suffered
by any Company Indemnified Party in connection with any third party action, assessment, claim, demand, proceeding or suit to the extent arising or resulting from
(a) the Client's negligence or willful misconduct; (b) the Client's breach of this Agreement; or (c) CREATIVE BIOLABS’ use, or alleged use, in the performance of
the Services in the conduct of the Project, of any Client Background Intellectual Property, Client Provided Materials or Client Provided Material Information
licensed or provided by the Client to CREATIVE BIOLABS for the purpose of performing the Services in the conduct of the Project.
10. Limited Warranty.
The Services Agreement (Quote) is a contract for services. CREATIVE BIOLABS’s sole warranty with respect to the Services is that CREATIVE BIOLABS will
perform all Services in accordance with the standard of performance set forth in Section 2 above. Client shall notify CREATIVE BIOLABS in writing of any claim
for a breach of such warranty by CREATIVE BIOLABS within one (1) month after delivery by CREATIVE BIOLABS of the last-to-deliver Deliverable relating to
such Services. The sole remedy of Client for breach of such warranty shall be to require CREATIVE BIOLABS to re-perform the Services (or such portion thereof
as may reasonably be required to be re-performed), and, in such event CREATIVE BIOLABS shall diligently pursue the re-performance of the Services or portions
thereof until completion, or, if CREATIVE BIOLABS cannot re-perform the Services (or such portion) in accordance with this limited warranty, then it shall refund
amounts paid by the Client for the applicable Service giving rise to the breach of warranty.
TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, IN NO EVENT SHALL CREATIVE BIOLABS BE LIABLE UNDER ANY LEGAL THEORY
(INCLUDING BUT NOT LIMITED TO CONTRACT, NEGLIGENCE, STRICT LIABILITY OR WARRANTY OF ANY KIND) AS A RESULT OF CREATIVE BIOLABS’
FAILURE TO PERFORM THE SERVICES IN ACCORDANCE WITH THIS WARRANTY FOR ANY DIRECT, INDIRECT, SPECIAL, INCIDENTAL,
CONSEQUENTIAL, OR EXEMPLARY DAMAGES, EVEN IF CREATIVE BIOLABS HAD NOTICE OF THE POSSIBILITY OF SUCH DAMAGES. TO THE
MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, THE WARRANTY SET FORTH IN THIS SECTION IS IN LIEU OF ANY AND ALL OTHER
WARRANTIES RELATING TO THE SERVICES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, CUSTOM, TRADE, QUIET ENJOYMENT, ACCURACY OF INFORMATIONAL CONTENT,
OR SYSTEM INTEGRATION, OR THAT THE USE OR SALE OF DELIVERABLES OR INFORMATION PROVIDED HEREUNDER WILL NOT INFRINGE OR
MISAPPROPRIATE ANY THIRD PARTY INTELLECTUAL PROPERTY RIGHT. TO THE MAXIMUM EXTENT PERMITTED BY LAW, CREATIVE BIOLABS’
LIABILITY TO CLIENT FOR BREACH OF ANY TERMS AND CONDITIONS OF THE SERVICES AGREEMENT (OTHER THAN ANY BREACH OF THE
WARRANTY CONTAINED IN THIS SECTION IN RESPECT OF WHICH ANY LIABILITY SHALL BE LIMITED TO RE-PERFORMANCE OR REFUND AS
SPECIFIED HEREIN) SHALL BE LIMITED TO DAMAGES (OTHER THAN INDIRECT, SPECIAL, INCIDENTAL, CONSEQUENTIAL, OR EXEMPLARY
DAMAGES) IN AN AMOUNT NOT TO EXCEED THE FEE PAID OR TO BE PAID BY CLIENT TO CREATIVE BIOLABS IN CONNECTION WITH THE
SERVICES.
11. Termination.
CREATIVE BIOLABS may terminate the Services Agreement in the event that (a) the Client breaches or fails to comply with any material provision of the Services
Agreement and, where the breach or failure is capable of being remedied, fails to remedy the breach or failure to the satisfaction of CREATIVE BIOLABS within
fifteen (15) days of receiving written notice thereof; (b) in the event CREATIVE BIOLABS has agreed to procure from a third party non-standard or custom Client
Materials specifically for use in the performance of Services and CREATIVE BIOLABS is unable to reach agreement with such third party on the terms and
conditions of such procurement, or the third party is unwilling or unable to provide the Client Materials for reasons beyond CREATIVE BIOLABS’ reasonable
control; or (c) in the event that any of the following actions occur in relation to the Client: an order is made for the winding up of the Client; a receiver or receiver
and manager of any property of the Client is appointed; a provisional liquidator of the Client is appointed; the Client is or is deemed by law to be unable to pay its
debts; the Client makes any arrangement or compromise with its creditors or members or with any class of its members or creditors; and/or the Client ceases to
carry on its business in the areas necessary for the performance of its obligations under the Services Agreement.
12. Choice of Law and Jurisdiction.
This Quotation shall be governed by and construed in accordance with the laws of the State of NY, U.S.A. Any litigation or other dispute resolution between the
parties relating to this Quotation shall take place in the U.S. District Court where Creative Biolabs is registered. The parties consent to the personal jurisdiction of
and venue in the state and federal courts within the State of NY.

16
Afuco™ Platform
Creative Biolabs Inc
ADDRESS: SUITE 203, 17 Ramsey Road, Shirley, NY 11967, USA
TEL: 1-631-357-2254
FAX: 1-631-207-8356
EMAIL: info@creative-biolabs.com
ADDRESS: 167-169 Great Portland Street, 5th Floor, London, W1W 5PE
TEL: 44-207-097-1828
EMAIL: info@creative-biolabs.com
https://adcc.creative-biolabs.com/
© 2021 Creative Biolabs

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