PharmaLegacy

TDAR to an antigen is a comprehensive immune function assay evaluating various aspects of immune responses, including antigen processing and presentation, B and T lymphocyte interactions, antibody production and cytokine-dependent isotype class switch (i.e., IgM to IgG specific antibody response).
The use of a TDAR assay is endorsed by regulatory agencies as a "default" immune function test for evaluation of the immuno-toxicity potential of new drug candidates.
TDAR is also employed to evaluate investigational drug efficacy in preclinical pharmacology studies, provide evidence of biological impact in clinical trials, and evaluate primary or secondary immunodeficiency diseases.
TDAR model in NHP provides a chance to overcome species specificity issue that biologics drug may have. NHP is also used in TDAR if it is deemed to be a more appropriate species for a particular small molecule (e.g., similarity of metabolism, better exposure, or immunity-related finding in standard toxicity studies only present in NHP).

The level of humanization (level of huCD45+ cells in peripheral blood) ranges between 40%-60% consistently. T cell immune-oncology checkpoint inhibitors PD-1 and PD-L1 antibodies (lead molecules from local R&D collaborators) demonstrated obvious inhibitory effects on the growth of HCC-827 human NSCLC cell line. PD-1 and PD-L1 antibodies stimulated the proliferation and differentiation of the human T cells in peripheral blood and accelerated the infiltration of human T cells into tumors.

GLP 10993 and CFDA 16886 Orthopedic Device Biocompatibility testing

We are able to assist with your IDE and 510(k) and SOP driven GLP quality assurance operations for your regulatory submission in the US, Europe and China.

For the 10993 and CFDA 16886 biocompatability testing prices are approximatly:
In-life study in rabbits (estimated at about @120 – 150 K USD)
The rest are at about $22,500 USD

Fulminant Hepatitis
* Fas Ab (Jo2)-induced liver failure
* Acetaminophen intoxication

Hepatitis B
* C57 BL/6J-Tg (AlblHBV) 44Bri/Jf4J transgenic mice model
* M-TgHBV transgenic mice model

Immune Response Related Hepatitis
* Con A-induced liver injury
* LPS-GalN-induced fulminant hepatitis

Liver Steatosis
- Alcohol-induced fatty liver
- Non-alcohol steatohepatitis (NASH)

MCD:
Induced after 8 weeks of MCD diet, the animals developed inflammation with presence of steatosis, hepatocellular ballooning and minute amount of fibrosis.

CDA-HSD model, which is a modified version of MCD. It is based on a diet not completely methacholine deficient plus some high fat component. This model seems to be able to resolve the body lose problem of MCD model. The induction of this model last for 6-8 weeks.

AMLIN model, which is totally based on high fat diet. It takes 36 weeks to develop.

Obesity model in Monkeys

UUO Induced Kidney Fibrosis in Rats

Non-human primate (NHP) models have closer phylogenetic relationship to human and the disease targets in NHP models share high cross-reactivity to the human target specific biological molecules which do not react with rodent counterpart. PharmaLegacy has developed and validated serials of NHP disease models, covering Inflammation/Autoimmune Diseases, Bone/Orthopedics, and Respiratory disease areas, to test pharmacological effects and mechanisms of candidate drugs esp. therapeutic monoclonal antibodies.

NHP Animal Disease Models

Non-human primate (NHP) models have closer phylogenetic relationship to human and the disease targets in NHP models share high cross-reactivity to the human target specific biological molecules which do not react with rodent counterpart. PharmaLegacy has developed and validated serials of NHP disease models, covering Inflammation/Autoimmune Diseases, Bone/Orthopedics, and Respiratory disease areas, to test pharmacological effects and mechanisms of candidate drugs esp. therapeutic monoclonal antibodies.

NHP Animal Disease Models

NHP Inflammation Models:

• NHP Asthma HDM Model

• NHP Liver Fibrosis, BDL

• NHP Colitis Model
  DSS
  Chemotherapy induced

• NHP Rheumatoid Arthritis Models
  Monkey CIA induced RA
  Anemia

• LPS induced Lung Injury

• NHP DTH Models

• TTx induced DTH

NHP Bone/Orthopedics Models:

• OVX induced Osteoporosis

• ACLT induced Osteoarthritis

• Bone Healing

• Bone Safety

Other NHP Models:

• FeCl3 induced Thrombosis

• Obesity

• Oncology osteosarcoma

Bleomycin Induced Skin Fibrosis in Mice

　◇Psoriasis-like inflammation
- IL-23-induced psoriasis-like inflammation in mice
- Imiquimod induced psoriasis-like inflammation in rats

◇Delayed Type Hypersensitivity (DTH)
- Oxazolone-induced DTH in mice
- DNFB-induced DTH in rats and mice
- Tetanus toxoid-induced DTH in monkeys

PharmaLegacy provides in vivo oncology models using more than 90 cell lines and tumor types in Humanized mice, syngeneic, Immuno-oncology, subcutaneous, orthotopic, and metastatic xenograft models. In addition, leukemia, lymphoma and myeloma models, and mouse syngeneic models are also available. We offer integrated and custom-tailored preclinical services, including but not limited to candidate screening, lead optimization, in vivo efficacy and biomarker validation in both small and large molecules’ drug discovery.
- >95 human tumor cell lines, >25 tumor types
- Subcutaneous, orthotopic and metastatic xenograft models
- Leukemia and lymphoma models
- Mouse syngeneic models and special tumor models
- Human primary tumor derived models
- Nude rate models, Combination chemotherapy & Radiation + treatment models
- Special focus: hepatocellular carcinoma (HCC), gastric cancer (GC), colon cancer, etc.

◇Colitis
- DSS-induced colitis in mice
- DSS-induced in monkeys
- DNBS-induced colitis in rats
- Chemotherapeutics induced colitis in rats and monkeys

• CCl4 -induced liver fibrosis and cirrhosis
  
• CCl4 -induced acute liver injury and fibrogenesis
  
• Bile duct ligation-induced liver fibrosis and cirrhosis in rodents and monkeys
  
• ANIT-induced cholestasis and fibrosis
  
• TAA
  
• ConA
  
• NASH
  

• Ovalbumin-induced asthma in rats and mice
  
• Ovalbumin-induced asthma in non-human primates
  
• House dust mite-induced asthma in rats and mice
  
• House dust mite-induced asthma in non-human primates

PharmaLegacy offers the clients a broad spectrum of high quality services in the areas of in vitro ADME, in vivo pharmacokinetics and bioanalysis services, with cost-efficiency and fast turnaround. The test articles range from small molecules to large molecules, such as protein and antibody. The animal species involved are non-human primate, canine, mice, rat, rabbit, guinea pig and mini pig.

　　Bioanalysis

◇ Method Transfer, Development and Validation
- LC-MS/MS (small molecules, peptides and protein)
- ELISA (antibody)
- HPLC (small molecules and oligonucleotides)

◇ Biological Matrix
- Plasma, serum and blood
- Urine, feces and bile
- Tissues and tumor specimens
- Cerebrospinal fluid
◇ In Vivo Dosing
- Intravenous (bolus/infusion)
- Intra-duodenal, intra-portal
- Oral, subcutaneous, intraperitoneal, intramuscular, dermal plus other routes 　

◇ Outputs
- Sample concentrations
- PK parameters (WinNonLin)

◇ Services
- Bioavailability
- Single and multiple dose PK
- Crossover studies
- Cassette PK for compound screening
- Dose ranging and proportionality
- BBB penetration
- Drug distribution in tissues
- Excretion studies
- PK study for formulation/form development
- Exploratory non-GLP TK studies
- PK/PD study in animal disease models
- DMPK study for IND filing

◇Cartilage Tissue Repair
　　•Intervertebral disc repair
　　•Intra-articular particulate injection
　　•Meniscectomy and ACL transection
　　•Osteochondral defect
　　•Pond Nuki model

• Adjuvant-induced arthritis in rats
  
• Collagen II-induced arthritis in rats and mice
  
• Collagen II-induced arthritis in monkeys
  

　◇Passive Cutaneous Anaphylaxis (PCA)
- PCA in rats and mice

FeCl3 Induced Arterial Thrombosis on Monkey

• A single dose of bleomycin-induced asthma in rats and mice
  
• Chronic multiple doses of bleomycin-induced asthma in rats and mice

◇Osteomyelitis
　　•Pyogen-induced and wear debris induced in rats, rabbits and dogs

◇Experimental Autoimmune Neuritis (EAN)
- SP-26-induced EAN in rats

Gouty Arthritis

• MSU-induced gouty arthritis in rats
  

　　◇Radioprotective activity in rats and mice
Integrated Drug Evaluation
- Cell-based Assays
- Clinical scoring
- Clinical Biochemical Analyzer
- Cytokine panel analysis
- Complete blood count (CBC)
- PK/PD Studies
- Immunohistochemistry/Histopathology

　◇Graft-Versus-Host Disease (GVHD)
- Allobone marrow transplantation induced acute GVHD in mice

• Arachidonic acid-induced ear edema in ICR mice
  
• Croton oil-induced ear edema in ICR mice
  
• Phorbol ester-induced ear edema in ICR mice
  
• Carrageen-induced paw edema in mice
  
• Testosterone induced benign prostatic hyperplasia
  
• Acetic acid induced pain in mice
  
• Cecal ligation and puncture induced sepsis in mice

System Lupus Erythematosus (SLE)

• SLE in NZB/W F1 mice
  
• SLE in MRL/lpr mice
  

PharmaLegacy offes non-GLP preclinical toxicological studies in various animal species.

• Single and repeated dose toxicity study (rodent and non-rodent)

  • LD50 study
    
  • MTD study
    
  • Dose escalation study
    
  • 7-day and 14-day DRF study
    
  • 1-month to 9-month sub-chronic and chronic toxicity study
    
  • Immunogenicity study
    
  • Toxicokinetics study (rodent and non-rodent)
    
  • Topical toxicity study
    
  • Irritation study
    
  • Sensitization study
    
  • Hemolysis study
    

• MBP-induced EAE in rats
  
• MOG-induced EAE in mice
  
• PLP-induced EAE in mice
  
• Cuprizone induced demyelination in mice
  

• LPS-induced acute lung inflammation in rats and mice
  
• LPS-induced acute lung inflammation in non-human primates
  

• OVA-induced allergic rhinitis in mice

◇Cough
• Citric acid-induced cough in guinea pigs

◇Ligament/Tendon
　　•Achilles', ACL, patella and rotator cuff segmental defect repair in dogs and sheep/goats

◇Bone Repair
　　•Bone void filler testing in rats, rabbits, mini-pigs, dogs and primates
　　•Calvarial, periodontal and long bone
　　•Spine fusion in rats, rabbits and primates

Bone Loss/Osteoporosis
　　•Rats, mice, dogs, monkeys and rabbits
- Estrogen-deficiency
- Steroid-induced
- Disuse
　　•Local injection to calvaria and long bone

• Zuker fatty rats
  
• Db/db mice
  
• High fat diet-induced type II diabetes in rats and mice
  
• STZ-induced type II diabetes in rats and mice
  
• Diabetic nephropathy
  
• Insulin

◇Liver Injury Regeneration
- Partial hepatectomy
- Bile duct ligation-induced liver fibrosis and cirrhosis
- ANIT-induced cholestasis and fibrosis
- Fas Ab (Jo2)-induced liver regeneration
- CCl4 -induced liver regeneration

　　◇Comedones
- Oleic acid-induced comedones in rabbits

◇Experimental Autoimmune Uveoretinitis (EAU)
- Bovine IRBP R16-induced EAU in rats