Working with world-leading
companies and academic
institutions across many
therapeutic areas, Abzena is proud
to offer its suite of complementary
services and technologies to enable
the development and manufacture
of better biopharmaceuticals
Abzena Sites & Technology Overview
San Diego, USA
Abzena has undergone a significant transformation in the past few years following the acquisition
of Antitope in 2013 and PacificGMP and TCRS in 2015. Bringing together these companies allows
Abzena to support customers’ projects seamlessly from lead optimisation and selection through
to GMP manufacturing for clinical trials.
MANUFACTURING
GMP manufacturing of biopharmaceuticals for
Phase I and Phase II clinical trials using single-use
equipment
Process development to improve yield and
optimise each step in the process for scale-up
Coventry, UK
R&D site for developing and synthesising
conjugation and PEGylation reagents
PolyPEG™ a low viscosity polymer to
make it easier to manufacture and inject
long acting therapeutic proteins
Bristol, USA
Toolbox of cytotoxic payloads, synthesis of
payload-linker combinations for ADCs, custom
synthesis of reagents and small molecules
Manufacture of ADCs for evaluation and
preclinical studies using ThioBridge™ or
other conjugation chemistries
Cambridge, UK
IMMUNOGENICITY ASSESSMENT
iTope and TCED™ to identify T cell epitopes
using a proprietary database and algorithm
CELL LINE DEVELOPMENT
Composite CHO™ to produce high
expressing cell lines for manufacture
EpiScreen™ for ex vivo assessment of the
immunogenicity of biopharmaceuticals
Biosimilar cell line development in CHO,
NS0 and SP2/0 including enhanced PQA
ANTIBODY & PROTEIN ENGINEERING
Composite Human Antibody™ technology
to humanise and deimmunise antibodies
BIOCONJUGATION
ThioBridge™ for the generation of more
stable and homogeneous ADCs
Composite Protein™ technology for
deimmunisation of therapeutic proteins
TheraPEG™, CyPEG™ and HiPEG™ for
linking polymers to therapeutic proteins to
extend their duration of action
Immunogenicity Assessment |
EpiScreen™
Preclinical immunogenicity assessment for lead
selection, risk mitigation or deimmunisation
• EpiScreen™ results correlate with reported anti-drug
antibody (ADA) responses in the clinic
• EpiScreen™ facilitates lead selection based on the
immunogenicity of whole proteins including mAbs and
other human and non-human protein therapeutics
• EpiScreen™ can map T cell epitopes allowing more
effective antibody humanisation and protein deimmunisation
EpiScreen™ time course T cell assay
The EpiScreen™ time course T cell assay is an accurate and sensitive way
to assess the immunogenicity of protein therapeutics. Each study uses
a donor cohort that best represents the distribution of HLA-allotypes
in the population. By measuring CD4+ T cell responses ex vivo, the
EpiScreen™ time course T cell assay assesses the strength and kinetics
of T cell responses to your protein therapeutic. These are benchmarked
against historical data for clinical products to provide an immunogenicity
risk assessment.
Immunomodulatory proteins
For proteins that directly modulate T cell activation, the EpiScreen™
DC:T cell assay is configured to prevent the direct stimulation of T cells,
in order to assess the overall immunogenicity.
Results correlate with clinical immunogenicity
Below: An analysis of 16 clinical-stage therapeutic proteins where the frequency
of donor responses by EpiScreen™ analysis demonstrates a correlation with
the average frequency of patients developing anti-drug antibodies reported in
clinical studies (Baker et al., 2007 and Barker et al., 2010)
EpiScreen donor response (%)
40
IFNalpha
R2 = 0.83
sTNFR1a
30
Alemtuzumab
Infliximab
IFNbeta
Hirudin
Vedolizumab
TPO
10
0
A33
Adalimumab
20
Palivizumab
Omalizumab
Etanercept
Bevacizumab
Cantuzumab Trastuzumab
0
10
20
30
Clinical immunogenicity (%)
40
50
EpiScreen™ T cell epitope mapping
The EpiScreen™ epitope mapping assay
uses synthetic 15mer peptides spanning the
protein sequence of interest to provide a
highly accurate map of CD4+ T cell epitopes.
Identification of T cell epitopes during the
pre-clinical development phase allows for
re-engineering of deimmunised variants
with a lower risk of immunogenicity. T
cell epitope mapping technology has
been applied to the deimmunisation of
monoclonal antibodies, enzymes, bacterial
proteins, toxins and non-human proteins.
iTope & TCED™
iTope™ and TCED™ in silico tools can be used to
rapidly screen proteins for potential immunogenicity.
The combination of both technologies provides a
more accurate prediction of T cell epitopes than
other in silico technologies that rely solely on MHC
class II binding analysis.
• Ideal for rapid screening of large numbers of samples to
identify potential leads for further development
• Aids in the design of deimmunised proteins and
antibodies
TCED™
TCED™ is a proprietary database of confirmed T cell epitopes
derived from EpiScreen™ T cell epitope mapping assays used to
identify T cell epitopes for removal. Sequences from proteins can
be analysed for homology to these known T cell epitopes, enabling
the rapid and accurate in silico identification of their potential to
produce an immunogenic response.
iTope™
iTope™ is an in silico tool which uses human HLA-DR MHC Class
II binding predictions to identify immunogenic sequences and to
design amino acids substitutions which reduce immunogenicity.
Right: Peptides spanning the test sequence
were tested as 9mer peptides in one amino acid
increments. The position of p1 anchor residues
comprises the first residue of an MHC class II
ligand core 9mer. Regions containing potentially
immunogenic peptides are indicated in left hand
columns where red indicates promiscuous high
affinity MHC class II binding peptides and yellow
indicates promiscuous moderate affinity MHC
class II binding peptides. In the “TCED” column,
regions representing closely homologous
peptides from the T cell epitope database are
shown in green.
1
T
2
A
3
S
4
F
5
p1
L
6 p1
p1 I
7
G
8
A
9
M
10
S
11
V
12
E
13
S
14
E
15
D
16
G
17
I
18
G
19
L
20
p1 Y
21
R
22
T
23
V
24
T
25
G
26
I
27
S
28
L
Mean Binding Score
High Affinity
Total Alleles Binding
B1*0101
B1*0102
B1*1501
B1*1502
B1*0301
B1*0305
B1*0306
B1*0309
B1*0401
B1*0405
B1*0404
B1*0405
B1*0408
B1*0410
B1*0421
B1*1101
B1*1102
B1*1104
B1*1107
B1*1114
B1*1120
B1*1128
B1*1301
B1*1304
B1*1307
B1*1321
B1*0701
B1*0801
B1*0802
B1*0804
B1*0806
B1*0813
B1*0817
B1*0101
Sequence
Promiscuous High
TCED
Residue number
TCED™ and iTope™ can be used together
to provide a more accurate evaluation of
potential immunogenicity. The combined
technology is typically used for rapid
analysis of multiple sequences in order to
identify a lead sequence with reduced risk
of containing T cell epitopes. In the figure
on the right a representation of results
obtained by iTope™ and TCED™ is provided.
Promiscuous Moderate
HLA - DR Allotypes
A powerful combination
5 3 0.62
18 9 0.6
27 24 0.65
4
6
0.58
2
0.58
13 3
0.58
12 6 0.6
20 18 0.69
2
0.55
5
3
0.6
3
0.64
1
3
0.57
Antibody & Protein Engineering |
Antibody Humanisation
Composite Human Antibody™ technology combines humanisation
and deimmunisation technologies to generate fully humanised
therapeutic antibodies devoid of CD4+ T cell epitopes.
• Rational sequence design avoids CD4+ T cell epitopes, resulting
in reduced immunogenicity compared to humanised and human
antibodies
• Sequence changes combined with structural integrity assessment
ensures excellent retention of affinity and specificity compared to the
starting monoclonal antibody
• T cell epitope avoidance is confirmed using the EpiScreen™ time course
T cell assay
• Successfully applied to over 60 antibodies with 11 antibodies in clinical
development
• The Composite Human Antibody™ technology improves on industry
standard humanisation and fully-human antibody technologies
Humanisation and deimmunisation in one
Composite Human Antibody™ technology creates fully-humanised antibodies that retain
the binding affinity and specificity of the starting monoclonal antibody and which are
also devoid of CD4+ T cell epitopes, thereby avoiding undesirable immunogenicity in
patients.
Through careful selection of human sequence segments and the application of in
silico tools, CD4+ T cell epitopes can be avoided to reduce the risk of immunogenicity.
Composite Human Antibodies™ are screened against the test antigen to ensure that the
affinity and specificity of the starting antibody is maintained.
Correct as of 1st April 2016
Currently 11 antibodies humanised using Composite Human Antibody™ technology are
in clinical development as shown below.
Company & product candidate
Target
Potential indications
Gilead Sciences – GS-5745
MMP-9
Gastric cancer, Crohn’s disease, ulcerative
colitis, RA, COPD
Gilead Sciences – Simtuzumab
LOXL2
Liver fibrosis (including NASH) & IPF
Opsona Therapeutics – OPN-305
TLR2
Delayed renal graft function &
myelodysplastic syndrome
Vascular Pharmaceuticals –
VPI-2690B
αVβ3
receptor
Diabetic nephropathy
NKT Therapeutics – NKTT120
iNKT cells
Sickle cell disease
Adheron Therapeutics – SDP 051
Cadherin 11
RA, fibrotic conditions, cancer
Therapure Innovations –
TBI 304H
CD163
Chemotherapy-induced anaemia
4 Undisclosed companies
Undisclosed
Undisclosed
Phase I
NASH = Non-alcoholic steatohepatitis; IPF = idiopathic pulmonary fibrosis; COPD = chronic obstructive pulmonary disease; RA = rheumatoid arthritis
Phase II
Phase III
Protein Deimmunisation
Composite Protein™ technology generates
therapeutic proteins designed to minimise
immunogenicity in patients without compromising
protein activity.
• T cell epitopes mapped and prioritised for removal
• Excellent retention of functionality and specificity
compared to the starting protein
• Proprietary technology, avoids other deimmunisation
patents
• Confirmation of T cell epitope avoidance determined
using EpiScreen™
“..We are delighted to
be working (Abzena)
to deimmunise our
protein warhead
using their proven
technology platform..”
Kurt Gehlsen
Research Corporation Technologies VP &
CSO
T cell epitope identified and removed
Composite Protein™ technology has improved upon the previous
deimmunisation technologies through the incorporation of
EpiScreen™ to more accurately identify and prioritise removal of T
cell epitopes.
Through the use of EpiScreen™, T cell epitopes (the primary drivers
of long lived, memory based immunogenicity) are identified and
ranked by magnitude and promiscuity. The T cell epitopes are then
removed from the protein using proprietary in silico tools and new
variants are designed.
Simultaneously, structure and homology analyses guide the
targeting and substitution of key amino acids in order to retain
the desired protein activity. Deimmunisation of the resulting
Composite Protein™ is confirmed by the EpiScreen™ time course T
cell assay as shown below.
Right: A wild-type (WT) protein and Composite
Protein™ generated from the WT protein were
tested in the EpiScreen™ time course T cell
assay. The WT protein was highly immunogenic
but following deimmunisation using
Composite Protein™ technology no significant
immunogenicity (less than 10% of donors
responding) was observed.
% Donors responding
Reducing Immunogenicity
40
Day 6
35
Day 7
Day 8
30
Day 9
25
20
15
10
5
0
WT Protein
Composite Protein
Protein Expression |
Cell Line Development
Abzena offers a variety of manufacturing cell line
packages to suite customers’ development needs,
from transient cell lines through to high expressing
working cell banks ready for cGMP manufacture.
• High expression levels of antibodies and proteins
• Seamless transition from cell line development to
in-house GMP production at Abzena’s US facility or
management of transfer to another manufacturer
• No downstream milestones or royalty payments
Stable cell line development
Stable cell lines capable of producing high yields of antibodies or
proteins are grown in suspension in chemically defined, serumfree medium. Transfection of the cells can be performed using our
pANT™ vector or a custom vector. Our manufacturing cell lines
have been successfully transferred to contract manufacturers and
scaled up in-house to produce cGMP material.
Maintaining high expression and integrity
Yield and product quality are key to cell line development and
Abzena has developed technologies, including Composite CHO™
and pANT™ vectors, to achieve the high expression levels of the
desired antibodies and proteins.
PQA assessment can also be undertaken at multiple stages
throughout the project to ensure product integrity and quality.
pANT™ vector
Abzena’s pANT™ vector maximises recombinant protein expression
through the use of a proprietary UTR (Untranslated Terminal
Region) to enhance protein production, and a modified dhfr gene
for the rapid amplification of vector copy numbers in the cells.
Proprietary vector:
•Modified 5’ UTRs for increased protein expression
•DHFR selection allows industry standard MTX amplification
•Driven by a strong CMV I/E promoter
For recombinant antibodies:
•Contains both heavy and light chain genes in a single vector
(right)
•Constant regions contained on genomic fragments (with
introns) for increased expression levels
•Selection of IgG sub-classess such as IgG1, IgG2 and IgG4 with
optional stability or functional enhancements
Mlu I
Hind III
BamH I
BssH II
pANT™ vector
Visualisation of a dual-chain pANT™ vector designed for
recombinant antibodies. Yellow sections indicate modified
5’ UTRs.
Biosimilar Development
Abzena offers CHO, NS0 and Sp2/0 biosimilar cell
line development programmes with bespoke quality
assessment tailored to individual projects.
•
•
•
•
•
•
High transcription vector system
Vector components fully sequenced and traceable
Highly efficient transfection process
Fully traceable host lines (CHO, NS0, Sp2/0 and others)
Host cell lines certified sterile and mycoplasma-free
Final optimised cell lines ready for cGMP manufacture
Developing biosimilars
Maintaining biosimilarity is critical for regulatory approval and Abzena
can help you achieve this by developing your biosimilar cell line using
the originator cell type. We have CHO, NS0, and Sp2/0 cell lines
adapted to serum-free growth for development programmes. During
development of the cell line we assess a range of product quality
attributes (PQA) to check consistency of these parameters with the
reference product.
Delivering on expectations
Yield and product quality are key to biosimilar development and
Abzena has developed technologies, including Composite CHO™
and pANT™ vectors, along with the experience to achieve the
high expression levels of the desired antibodies and proteins. We
ensure all materials used to develop the cell line are free of animalderived products and the cells are grown in a chemically defined
medium. Abzena is experienced in the transfer of cell lines to cGMP
manufacturing facilities to expedite scale-up.
Product quality attributes (PQA) assessment
To ensure consistency during the generation of manufacturing cell lines we have an approach whereby cell line and product
quality are assessed at multiple stages as an integral part of the cell line development process.
Product aggregation
•Analysis of product aggregation, subunit dissociation or
degradation
•Intact mass analysis
•Assessment of sample purity and suitability of purification
Product integrity
•Protein sequence confirmation
•Confirmation of full protein and subunit mass
•Analysis for loss of subunit or fusion partner
•Analysis of potential degradation
• Analysis for site specific oxidations or deamidations
Facilities
Product glycan profiling
•N-glycan peak identification
•Monosaccharide analysis
•Sialic acid analysis
•Fucosylation
•Matching of specific glycan profile to innovator
product
Product activity
•Confirmation of binding characteristics
•Confirmation of activity/functionality
•Assessment of effector functions (ADCC/CDC)
for antibodies
Abzena ensures minimal risk of cross-contamination through dedication of specific equipment to individual projects. Cell
lines are stored under liquid nitrogen using facilities that offer 24-hour security with power and liquid nitrogen backup.
Bioconjugation |
Antibody Drug Conjugates
Abzena offers optional use of ADC development
from concept to manufacture including ThioBridge™
to create less heterogeneous ADCs with better
stability.
Abzena provides its ADC services and technologies from two
sites in Bristol, USA and Cambridge, UK.
Conjugation
ThioBridge™
ThioBridge™ is Abzena’s proprietary conjugation technology that
is used to attach a range of drug payloads, using either cleavable
or non-cleavable linkers, to an antibodies or other targeting
molecules through accessible disulfide bonds. The technology
has been applied to a variety of antibodies to generate stable
and homogeneous ADCs with 4 drugs attached and Fab drug
conjugates with 1 drug attached.
Homogeneity
• 80-90% DAR 4 can be achieved with IgG1 antibodies
• Antibody re-engineering to introduce conjugation sites
is not necessary if ThioBridge™ is used.
• Almost complete conversion to ADC – minimal or no
unconjugated antibody
Flexibility
• Compatible with a wide range of payloads and virtually
any type of antibody format containing accessible
disulfide bonds
• Compatible with the main payload release mechanisms
(cleavable and non-cleavable linkers)
Stability
• Structural stability of the antibody is maintained by
re-bridging disulfide bonds
• Stable link between antibody and payload
Manufacture
• Conjugation designed to be a simple, scalable, and
reproducible, one-pot process
• ADCs easier to characterise due to their greater
homogeneity
• Enhanced solubility and reduced propensity to
aggregate due to linker format
Other conjugation and spacer technologies
Abzena can also provide a selection of cleavable and non-cleavable linkers and spacer molecules for lysine, cysteine and azide
conjugation technologies among others. Partners can also provide us with their own linker reagents to perform conjugations.
Payloads
Abzena has a variety of highly potent payloads in stock for advancing its clients’ ADC projects. Abzena has more than 20 different
payloads in its toolbox for preparing conjugates which include:
•
•
•
•
Dolastatin-10 and auristatin analogs
Duocarmycin analogs
Maytansine analogs
PBD dimer analogs
Abzena conducts all work with highly toxic/cytotoxic compounds in its specially designed containment laboratory.
Analytics and Characterisation
Abzena’s state-of-the-art labs are equipped with an array of
analytical and preparative HPLC instruments and columns
allowing us to handle the most difficult separations.
This, in conjunction with our LC/MS and MALDI -ToF
mass spectrometers and 500-MHz and 300-MHz NMR
spectrometers, gives us the capability to offer our clients
valuable and reliable analytical services. We are continually
adding additional instrumentation in order to provide a
seamless, uninterrupted operation.
• Analytical and preparatory HPLC method development
• NMR analysis (300 MHz, 500 MHz, 1H,13C, 31P, 19F,
multidimensional)
• Size-exclusion/gel-filtration chromatography
• LC-MS analysis
• GC-MS with headspace analysis
•
•
•
•
•
•
Chiral separations
Stability studies at variable temperature and humidity
Optical rotations
Purity determinations by HPLC
Ion-exchange chromatography
Protein NMR spectroscopy
Abzena experience in characterisation and validation assay ensures that we can fully test and validate ADC’s during and post
production:
Target Validation
• Target binding affinity
• ADC internalization
• Homo-Hetero-dimerization
• Validated and quantitative measurements of cytotoxin
and/or ADC
Scale up and Manufacturing
Abzena currently has the capability to produce upto 100
g of toxin, 50 g of toxin-linker and upto 10 g of antibody
drug conjugate. Abzena will invest in expanding its facilities
to enable GMP manufacture of up to 100 g of ADC during
2016.
Scale up
• Route design and optimization
• Trouble-shooting
• Process optimization (avoidance of chromatography,
solvent minimization, impurity profiles, avoidance of
potential genotoxic reagents, and manufacturability)
• World-wide sourcing for best quality and cost
Manufacturing
• Non-GMP batches for GLP Tox studies
• 10 g toxin
• 50 g toxin-linker, 10 g of ADC
• Full batch records for regulatory submission
• Tech-transfer for multi-kg GMP scale
• See page 14 for GMP antibody manufacture
Mechanism of Action
• ADCC and CDC - Cytotoxicity assays
• Cell viability and cell death
• Cell proliferation
• Cell adhesion, migration and invasion
• Cytotoxin release
Optimisation of Pharmacokinetics
Abzena’s range of site-specific conjugation
technologies can optimise the pharmacokinetics (PK)
and pharmacodynamics (PD) of therapeutic peptides
and proteins, including antibody fragments and
other protein scaffolds.
CyPEG™ - cysteine conjugation
CyPEG™ is a conjugation technology for site-specific
conjugation of polymers at a thiol side-chain on a free
cysteine. The thiol residue on a cysteine readily undergoes
selective and efficient conjugation. Proteins or peptides
that do not have a cysteine can be engineered to provide a
specific site for conjugation using CyPEG™.
HiPEG™ - conjugation at polyhistidine
HiPEG™ provides site-specific conjugation of polymers
at histidine sequences expressed within or at the N or C
terminal ends of a protein. Conjugation at the terminus of
the protein can have the advantage of reducing the shielding
effect of the PEG on the functional part of the protein
thereby minimising the effect on its activity.
TheraPEG™ - disulfide conjugation
TheraPEG™ is a technology for attaching polymers, such as
PEG, to proteins through site-specific conjugation at disulfide
bonds. TheraPEG™ has the flexibility to conjugate a range of
PEG formats, including linear and branched PEG and Abzena’s
low viscosity polymer, PolyPEG™.
PolyPEG™ - modular polymer
PolyPEG™ is a novel low viscosity polymer comprising a
polymethacrylate backbone with short PEG side chains that
form a comb-like structure. PolyPEG™ can be conjugated
to therapeutic proteins to extend their in vivo half-life.
PolyPEG™ is available in a range of molecular weights
enabling the pharmacokinetics and pharmacodynamics of
the conjugated protein to be optimised.
• Alternative to linear and branched polymers where
viscosity is an issue for manufacture or administration
• Modular architecture and range of conjugation
chemistries available for optimal application of the
technology
•
Small Molecule |
Custom Synthesis
Abzena’s team of experienced organic chemists
has tackled a variety of complex molecules ranging
from mg to g scale, common requests include:
•
•
•
•
•
•
•
Chemical intermediates
Drug metabolites
Process impurities
Degradants
Reference compounds
Preclinical drug candidates
Other organic molecules from diverse industries
Manufacture
Manufacturing and scale up
Abzena currently has the capability to scale up multi-step
procedures up to 100 g quantities of target material.
Scale up
• Route design and optimization
• Trouble-shooting
• Process optimization (avoidance of chromatography,
solvent minimization, impurity profiles, avoidance of
potential genotoxic reagents, and manufacturability)
• World-wide sourcing for best quality and cost
Manufacturing
• Non-GMP batches for GLP toxicity studies
• In-house manufacturing up to 100 g
• Full batch records for regulatory submission
• Tech-transfer for multi-kg GMP scale
High Potency
Capacity to produce 25-100 g of highly potent and cytotoxic
small molecules.
Biologics Manufacturing |
Process Development
Abzena are experts in upstream and downstream
process development. These services can stand
alone or be integrated into preclinical a nd clinical
manufacturing projects.
The focus is on improving yield and consistency
during the manufacturing process.
Upstream process development
• Cell line expansion and research cell banking
• Process scale-up from 100ML to 500 litres in batch and
fed-batch
• Development of upstream processes for single-use
bioreactors
Downstream process development
• Optimisation of harvest, clarification, concentration,
viral clearance, purification (capture & polishing) and
formulation
• Development and scale-up with an emphasis on closed
systems employing single-use technology
Single use technology advantages
• Eliminates risk of cross-contamination
• Lower cost as a result of fewer infrastructure
requirements such as purified water systems and steam
generators
• Quick turn-around time between runs
• Less complex minimising engineering requirements
resulting in the elimination of clean-in-place or steamin-pace operations
Taking full advantage of single-use technology Abzena can
rapidly scale-up y our process from 1L to 15,000L with maximum
flexibility.
GMP Manufacturing
Abzena provides cGMP production for
recombinant proteins, antibodies, gene therapy
products and vaccines for use in preclinical and
phase I and II clinical trials.
Abzena has extensive experience in the use of
single-use technology which provides flexibility
in the production process. The services provided
include:
• Production of products for use in preclinical, Phase I
and II clinical trials
• Mammalian protein expression from 1L to 500L in
batch/fed batch mode and up to 15,000L in perfusion
culture
• Microbial protein expression at up-to 100L scale
• Master, Working and End of Production Cell Banks in
100, 200 and 300 vial configurations
• Analytical development and validation
• Final Fill/Finish of Drug Product to 2000 vials
• Release of Drug Product
• Stability testing
Manufacturing compliance and facilities
• Licensed by California FDB and registered with the US
FDA​
• Over 30 successful site audits​
• 1300 m2 state-of-the-art facility​
• ISO Class 5, ISO Class 7, ISO Class 8 controlled
environments​
• Multiple manufacturing production suites​
• Development laboratories​
• Separate quality control/analytical laboratories​
• Internal clean room expansion capabilities
Regulatory affairs support
As an integral part of manufacturing under GMP standards,
Abzena creates document packages suitable to support regulatory
approval for use in human clinical trials.
Cambridge, UK
San Diego, CA
Bristol, PA
Babraham Research Campus
Babraham
Cambridge CB22 3AT
United Kingdom
Tel: +44 1223903498
8810 Rehco Road, Suite E
San Diego, CA 92121
United States
Tel: +01 858-550-4094
360 George Patterson Blvd.
Suite 101E
Bristol, PA 19007
United States
Tel: +01 215-788-3603