Burfiralimab - ImmuneMed
Alternative Names: hzVSF; hzVSF-v13; IgG4 - ImmuneMedLatest Information Update: 15 Mar 2024
At a glance
- Originator ImmuneMed
- Class Anti-infectives; Anti-inflammatories; Antipsoriatics; Antivirals; Hepatoprotectants; Immunoglobulins; Monoclonal antibodies; Skin disorder therapies
- Mechanism of Action Immunomodulators; Virus replication inhibitors
-
Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
- Available For Licensing Yes
Highest Development Phases
- Phase II COVID-19 pneumonia; Hepatitis B
- Research Alcoholic hepatitis; Non-alcoholic steatohepatitis; Psoriasis; Scleroderma
- No development reported Pneumonia
Most Recent Events
- 12 Mar 2024 ImmuneMed plans a phase II trial for Rheumatoid arthritis in Netherlands (IV, infusion) in March 2024 (NCT06306339)
- 14 Feb 2024 ImmuneMed terminates a phase II trial in COVID-19 pneumonia (Adjunctive treatment, In adults, In the elderly) in South Korea (IV) as a new study combining Phase III clinical trials has been planned (NCT04679350)
- 28 Jan 2024 No recent reports of development identified for phase-I development in COVID-19 pneumonia in Australia (IV)
Development Overview
Introduction
A humanised virus suppressing factor variant 13, designated as burfiralimab (formerly hzVSF v13), is being developed by ImmuneMed, for the treatment of hepatitis B, pneumonia associated with influenza virus infections, COVID-19 pneumonia, alcoholic hepatitis, non-alcoholic steatohepatitis, scleroderma and psoriasis. Clinical development is underway in South Korea, Indonesia, Australia, Russia and Italy for COVID-19 pneumonia. Clinical development for pneumonia associated with influenza virus infections is underway in South Korea. Clinical development for hepatitis B is underway in South Korea. Early research for alcoholic hepatitis, non-alcoholic steatohepatitis, scleroderma and psoriasis is underway in South Korea.
Burfiralimab is an endogenous broad-spectrum antiviral and a monoclonal antibody immunoglobulin G4 (IgG4), developed using ImmuneMed's antibody and antigen discovery technologies. The antibody discovery platform enables the company to develop and discover antibodies with specificity for particular serotypes, species, and genera. The antigen discovery technology is used for discovering of both serotype-specific and group-specific antigens. The hzVSF reacts to VSF receptor (VR), a protein that is expressed only on virus-infected cells. HzVSF acts as a ligand to VR, and once engaged, it inhibits viral proliferation and suppresses infection-related inflammation that affects cell signaling pathways.
As of September 2018, ImmuneMed is seeking partners for licensing-out the drug for progressing the development (ImmuneMed website, September 2018).
As at April 2023, no recent reports of development had been identified for clinical-Phase-Unknown development in COVID-19 pneumonia in South Korea (IV).
As at January 2024, no recent reports of development had been identified for phase-I development in COVID-19 pneumonia in Australia (IV), phase-I development in Pneumonia in South Korea (IV).
Company Agreements
In December 2011, Lonza entered into a research and development agreement with ImmuneMed Inc, for the in silico screening followed by de-immunisation of their virus suppressing factor (VSF), being developed for the treatment of viral infections, including encephalomyocarditus, influenza virus and hepatitis. Under the terms of the agreement, Lonza will perform an immunogenicity risk assessment using their latest version of their T-cell epitope prediction engine, Epibase™. The preclinical assessment will be performed at Lonza's protein services and development facility in the UK. [1]
Key Development Milestones
COVID-19 pneumonia
In February 2024, as a new study combining Phase III clinical trials has been planned, ImmuneMed terminated a phase II trial that was intended to evaluate the efficacy and safety of burfiralimab compared to standard of care after intravenous administration with add-on standard of care in patients with COVID-19 pneumonia (IM_hzVSF_v13-0004; NCT04679350). This randomised, double-blind trial was initiated in March 2021 and enrolled 1 patient in South Korea [2] .
In August 2019, ImmuneMed completed a phase II trial that evaluated the efficacy and confirm the safety of the concomitant administration of the standard of care and burfiralimab in patients with COVID-19 pneumonia (hzVSF-v13-0007; NCT04679415). The randomised, double blind trial was initiated in December 2020 and enrolled 63 patients in Indonesia [3] .
In October 2021, ImmuneMed completed a phase II trial that investigated safety and efficacy of burfiralimab in patients with COVID-19 pneumonia (NCT04676971;hzVSF_v13-0006). The randomised, double blind trial was initiated in December 2020 and enrolled 115 patients in Russia and Italy. In December 2020, the company had also announced the approval for phase II trial in Italy, which was followed by Russia, Indonesia and Korea [4] [5] .
In December 2020, ImmuneMed announced that a phase I trial in patients with COVID-19 pneumonia is underway in Australia [4]
In March 2020, The Korean Ministry of Food and Drug Safety (MFDS) approved the use of burfiralimab for COVID-19 pneumonia treatment for individual patient at Yonsei University Hospital. The application for treatment use is the compassionate use system allowing doctors or companies to apply for and receive approval from the MFDS for individual or multiple patients who do not have an alternative treatment. Earlier, the two pneumonia patients who were administered the drug were given 2 or 3 doses of hzVSF and within 10 days, the virus disappeared and their pneumonia improved, eventually making a full recovery. Three patients had severe conditions requiring ventilator and ECMO treatment due to deteriorating pneumonia despite prescribing Kaletra, but showed rapid improvement after hzVSF administration. No side effects associated with VSF have been reported in these 7 pneumonia patients [6] .
In March 2020, ImmunoMed released preclinical data for coronavirus infections [6] .
Pneumonia [associated with influenza virus infections]
As of December 2020, ImmunMed completed a phase I trial of burfiralimab for Influenza induced pneumonia (ImmuneMed pipeline, December 2020).
Hepatitis B
In January 2022, ImmuneMed initiated a phase II trial to evaluate the efficacy and safety of oral antiviral agents/hzvsf-v13 combination therapy vs oral antiviral monotherapy in chronic hepatitis B patients (IM_hzVSF-v13-0003; NCT05808335). The double-blind, randomised, placebo-controlled trial intends to enroll approximately 32 patients in South Korea [7] .
As of December 2020, burfiralimab is in phase II IND progress for Hepatitis B and COVID-19 pneumonia in South Korea and other countries (ImmuneMed pipeline, December 2020).
Other studies
In July 2022, ImmuneMed initiated a phase I trial that evaluated the safety, tolerability and pharmacokinetics (PK) characterization of burfiralimab with single and multiple doses (intravenous and subcutaneous) compared to placebo in healthy subjects (NCT04817202; hzVSF_v13-0002). This randomised, double blind trial was initiated in September 2020 and enrolled 72 participants in Australia [8] .
In February 2020, ImmuneMed completed a phase I trial that evaluated the safety, tolerability and pharmacokinetics of burfiralimab in volunteers (IM_hzVSF_v13-0001; NCT03653208). The randomised, double blind trial was initiated in November 2018, and enrolled 56 healthy adults in South Korea [9] . There was no serious adverse event up to the highest dose of 1,200 mg [6] .
As of December 2011, preclinical development for viral infections including influenza and hepatitis was underway in South Korea [1] [10] .
In animal models, hzVSF inhibited pathological activity and improved clinical symptoms.
Patent Information
In April 2009, the USPTO granted an US patent number US 7 514 082 B2 to ImmuneMed, entitled "Anti-viral VSF protein and hybridoma producing the same", related to a virus suppressing factor (VSF) protein having antiviral activity against various viruses and a hybridoma secreting such a VSF protein. The patent is related to a pharmaceutical composition comprising the VSF protein and a method for prevention or treatment of viral infections in humans and animals, using such a pharmaceutical composition [11] .
ImmuneMed has a pending US patent application number US 20 050 080 236 A1, entitled "Novel anti-viral VSF protein and hybridoma producing the same", related to a virus suppressing factor (VSF) protein having antiviral activity against various viruses and a hybridoma secreting such a VSF protein. The patent is related to a pharmaceutical composition comprising the VSF protein and a method for prevention or treatment of viral infections in humans and animals, using such a pharmaceutical composition. The patent was filed in April 2005 [12] .
In March 2004, ImmuneMed was granted a Korean patent number 0425030, entitled "Novel anti-viral VSF protein and hybridoma producing the same", related to a virus suppressing factor (VSF) protein having antiviral activity against various viruses and a hybridoma secreting such a VSF protein.
ImmuneMed has a pending patent application number WO 03 064 461 A1, entitled "Novel anti-viral VSF protein and hybridoma producing the same", related to a virus suppressing factor (VSF) protein having antiviral activity against various viruses and a hybridoma secreting such a VSF protein. The patent was filed in August 2003 [13] .
Drug Properties & Chemical Synopsis
- Route of administration IV, Parenteral, SC
- Formulation unspecified
- Class Anti-infectives, Anti-inflammatories, Antipsoriatics, Antivirals, Hepatoprotectants, Immunoglobulins, Monoclonal antibodies, Skin disorder therapies
- Target Virus replication
- Mechanism of Action Immunomodulators; Virus replication inhibitors
-
WHO ATC code
A05B-A (Liver therapy)
D11A (Other Dermatological Preparations)
J05 (Antivirals for Systemic Use)
J05A-P (Antivirals for treatment of HCV infections)
-
EPhMRA code
A5B (Hepatic Protectors, Lipotropics)
D11 (Other Dermatological Preparations)
J5 (Antivirals for Systemic Use)
J5B1 (Viral hepatitis products)
J5B3 (Herpes antivirals)
J5B4 (Influenza antivirals)
- CAS Registry Number 2460809-80-5
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Alcoholic hepatitis | - | - | Research | South Korea | Parenteral / unspecified | ImmuneMed | 27 Jan 2021 |
| COVID-19 pneumonia | with standard of care | Adjunctive treatment | Phase II | Italy, Russia, South Korea | IV / unspecified | ImmuneMed | 18 Mar 2021 |
| COVID-19 pneumonia | - | - | Phase II | Indonesia | IV / unspecified | ImmuneMed | 17 Dec 2020 |
| COVID-19 pneumonia | - | - | No development reported (I) | Australia | IV / unspecified | ImmuneMed | 28 Jan 2024 |
| COVID-19 pneumonia | Compassionate use | - | No development reported (Clinical) | South Korea | IV / unspecified | ImmuneMed | 28 Apr 2023 |
| Hepatitis B | - | Combination therapy | Phase II | South Korea | IV / unspecified | ImmuneMed | 11 Jan 2022 |
| Non-alcoholic steatohepatitis | - | - | Research | South Korea | Parenteral / unspecified | ImmuneMed | 27 Jan 2021 |
| Pneumonia | associated with influenza virus infection | - | No development reported (I) | South Korea | IV / unspecified | ImmuneMed | 28 Jan 2024 |
| Psoriasis | - | - | Research | South Korea | Parenteral / unspecified | ImmuneMed | 27 Jan 2021 |
| Scleroderma | - | - | Research | South Korea | Parenteral / unspecified | ImmuneMed | 27 Jan 2021 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| ImmuneMed | Originator | South-Korea |
| ImmuneMed | Owner | South-Korea |
| Lonza | Collaborator | Switzerland |
Licensing Availability
| Licensing Organisation | Available Indication | Available Phase | Region | Date |
|---|---|---|---|---|
| ImmuneMed | - | Clinical Phase Unknown | - | 03 Sep 2018 |
Scientific Summary
Pharmacodynamics
The inflammatory cytokine production was inhibited after administration of burfiralimab in experimental coronavirus-infected mice. Reduction in IFN-gamma, MCP-1, IL-6 and TNF-alpha were observed characteristically. Burfiralimab increases the natural healing power of cells to suppress viral replication and reduce excessive immune response and inflammation, thereby showing therapeutic effect [6] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Mar 2024 | Trial Update | ImmuneMed plans a phase II trial for Rheumatoid arthritis in Netherlands (IV, infusion) in March 2024 (NCT06306339) | 15 Mar 2024 |
| 30 Jun 2021 | Trial Update | ImmuneMed plans a phase II study in COVID-19 pneumonia in USA [IV] in first half of 2021 [4] | 05 Jan 2021 |
| 01 Mar 2021 | Trial Update | ImmuneMed plans a phase II trial for COVID-19 pneumonia [IV, Injection] in South Korea in March 2021 (NCT04679350) (331824) | 05 Jan 2021 |
| 31 Dec 2020 | Trial Update | ImmuneMed plans a phase II study in COVID-19 pneumonia (Adjunctive therapy) in Indonesia in December 2020 (IV) (NCT04679415) (700331824) | 20 Jan 2021 |
| 31 Oct 2018 | Trial Update | ImmuneMed plans a phase I trial for Infections (In volunteers) (IV) in October 2018 (NCT03653208) (700299385) | 11 Dec 2018 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 12 Mar 2024 | Trial Update | ImmuneMed plans a phase II trial for Rheumatoid arthritis in Netherlands (IV, infusion) in March 2024 (NCT06306339) Updated 15 Mar 2024 |
| 14 Feb 2024 | Trial Update | ImmuneMed terminates a phase II trial in COVID-19 pneumonia (Adjunctive treatment, In adults, In the elderly) in South Korea (IV) as a new study combining Phase III clinical trials has been planned (NCT04679350) Updated 26 Feb 2024 |
| 28 Jan 2024 | Phase Change - No development reported | No recent reports of development identified for phase-I development in COVID-19 pneumonia in Australia (IV) Updated 28 Jan 2024 |
| 28 Jan 2024 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Pneumonia in South Korea (IV) Updated 28 Jan 2024 |
| 28 Apr 2023 | Phase Change - No development reported | No recent reports of development identified for clinical-Phase-Unknown development in COVID-19 pneumonia in South Korea (IV) Updated 28 Apr 2023 |
| 07 Jul 2022 | Trial Update | ImmuneMed completes a phase I trial (In volunteers) in Australia (IV) (NCT04817202) Updated 01 Mar 2024 |
| 07 Jul 2022 | Trial Update | ImmuneMed completes a phase I trial (In volunteers) in Australia (SC) (NCT04817202) Updated 01 Mar 2024 |
| 11 Jan 2022 | Phase Change - II | Phase-II clinical trials in Hepatitis B (Combination therapy) in South Korea (IV) (NCT05808335) Updated 25 Apr 2023 |
| 28 Oct 2021 | Trial Update | ImmuneMed completes a phase II trial in COVID-19 pneumonia (Adjunctive treatment) in Italy and Russia (IV) (NCT04676971) (EudraCT2020-003614-13) Updated 17 Dec 2021 |
| 19 Aug 2021 | Trial Update | ImmuneMed completes a phase II trial in COVID-19 pneumonia (Adjunctive therapy) in Indonesia in December 2020 (IV) (NCT04679415) Updated 30 Aug 2021 |
| 18 Mar 2021 | Phase Change - II | Phase-II clinical trials in COVID-19 pneumonia (Adjunctive treatment, In adults, In the elderly) in South Korea (IV) (NCT04679350) Updated 06 Sep 2021 |
| 27 Jan 2021 | Phase Change | Early research in Alcoholic hepatitis in South Korea (unspecified route) before January 2021 (ImmuneMed pipeline, January 2021) Updated 27 Jan 2021 |
| 27 Jan 2021 | Phase Change | Early research in Non-alcoholic steatohepatitis in South Korea (unspecified route) before January 2021 (ImmuneMed pipeline, January 2021) Updated 27 Jan 2021 |
| 27 Jan 2021 | Phase Change | Early research in Psoriasis in South Korea (unspecified route) before January 2021 (ImmuneMed pipeline, January 2021) Updated 27 Jan 2021 |
| 27 Jan 2021 | Phase Change | Early research in Scleroderma in South Korea (unspecified route) before January 2021 (ImmuneMed pipeline, January 2021) Updated 27 Jan 2021 |
| 23 Dec 2020 | Trial Update | Burfiralimab is in phase II IND progress for Hepatitis B and COVID-19 pneumonia in South Korea and other countries (ImmuneMed pipeline, December 2020) Updated 27 Jan 2021 |
| 23 Dec 2020 | Phase Change - I | Phase-I clinical trials in Pneumonia (associated with influenza virus infections) in South Korea (IV) before December 2020 (ImmuneMed pipeline, December 2020) Updated 23 Dec 2020 |
| 23 Dec 2020 | Trial Update | ImmuneMed completes a phase I trial in Pneumonia (associated with influenza virus infections) (IV) in South Korea prior to December 2020 (ImmuneMed pipeline, December 2020) Updated 23 Dec 2020 |
| 22 Dec 2020 | Trial Update | ImmuneMed plans a phase II study in COVID-19 pneumonia (Adjunctive therapy) in Indonesia in December 2020 (IV) (NCT04679415) Updated 20 Jan 2021 |
| 22 Dec 2020 | Trial Update | ImmuneMed plans a phase II trial for COVID-19 pneumonia [IV, Injection] in South Korea in March 2021 (NCT04679350) Updated 05 Jan 2021 |
| 20 Dec 2020 | Trial Update | ImmuneMed plans a phase II study in COVID-19 pneumonia in USA [IV] in first half of 2021 [4] Updated 05 Jan 2021 |
| 20 Dec 2020 | Phase Change - I | Phase-I clinical trials in COVID-19 pneumonia in Australia (IV), prior to December 2020 [4] Updated 24 Dec 2020 |
| 20 Dec 2020 | Regulatory Status | ImmuneMed intends to submit Investigational New Drug application to the US FDA for a phase II trial in USA [4] Updated 24 Dec 2020 |
| 18 Dec 2020 | Phase Change - II | Phase-II clinical trials in COVID-19 pneumonia (Adjunctive treatment) in Italy (IV) (NCT04676971) (EudraCT2020-003614-13) Updated 17 Dec 2021 |
| 18 Dec 2020 | Regulatory Status | ImmuneMed received approval for phase II trial in Italy [4] Updated 24 Dec 2020 |
| 18 Dec 2020 | Regulatory Status | ImmuneMed received approval for phase II trial in Russia, Indonesia and Korea, prior to December 2020 [4] Updated 24 Dec 2020 |
| 17 Dec 2020 | Phase Change - II | Phase-II clinical trials in COVID-19 pneumonia in Indonesia (IV) (NCT04679415) Updated 20 Jan 2021 |
| 11 Dec 2020 | Phase Change - II | Phase-II clinical trials in COVID-19 pneumonia (Adjunctive treatment) in Russia (IV) (NCT04676971) Updated 23 Dec 2020 |
| 16 Sep 2020 | Trial Update | ImmuneMed initiates enrolment in a phase I trial (In volunteers) in Australia (IV) (NCT04817202) Updated 01 Mar 2024 |
| 16 Sep 2020 | Trial Update | ImmuneMed initiates enrolment in a phase I trial (In volunteers) in Australia (SC) (NCT04817202) Updated 01 Mar 2024 |
| 28 Apr 2020 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Hepatitis-B in South Korea (IV) Updated 28 Apr 2020 |
| 30 Mar 2020 | Phase Change - Clinical | Clinical trials in COVID-19 pneumonia in South Korea (IV) before March 2020 [6] Updated 02 Apr 2020 |
| 30 Mar 2020 | Regulatory Status | ImmunoMed files for the use of burfiralimab for use in treatment of 25 patients with COVID-19 pneumonia in South Korea [6] Updated 02 Apr 2020 |
| 30 Mar 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in Covid-19 pneumonia released by ImmunoMed [6] Updated 02 Apr 2020 |
| 30 Mar 2020 | Trial Update | Immunomed plans clinical trials for COVID-19 pneumonia in South Korea and other countries [6] Updated 02 Apr 2020 |
| 27 Mar 2020 | Regulatory Status | The Korean Ministry of Food and Drug Safety (MFDS) approves burfiralimab for compassionate use in treatment of COVID-19 pneumonia in South Korea [6] Updated 02 Apr 2020 |
| 29 Feb 2020 | Trial Update | ImmuneMed completes a phase I trial in Viral infections (In volunteers) in South Korea (IV) (NCT03653208) Updated 12 Apr 2021 |
| 29 Nov 2018 | Phase Change - I | Phase-I clinical trials in Viral infections (In volunteers) in South Korea (IV) (NCT03653208) Updated 11 Dec 2018 |
| 03 Sep 2018 | Trial Update | ImmuneMed plans a phase I trial for Infections (In volunteers) (IV) in October 2018 (NCT03653208) Updated 11 Dec 2018 |
| 03 Sep 2018 | Licensing Status | Burfiralimab is available for licensing as of 03 Sep 2018. http://immunemed.co.kr/ Updated 07 Sep 2018 |
| 08 Dec 2011 | Phase Change - Preclinical | Preclinical trials in Hepatitis B in South Korea (IV) [1] [10] Updated 10 Sep 2018 |
| 08 Dec 2011 | Phase Change - Preclinical | Preclinical trials in Influenza virus infections in South Korea (IV) [1] [10] Updated 10 Sep 2018 |
| 08 Dec 2011 | Phase Change - Preclinical | Preclinical trials in Viral infections in South Korea (IV) [1] [10] Updated 10 Sep 2018 |
| 07 Apr 2009 | Patent Information | ImmuneMed has patent protection for pharmaceutical composition of an anti-viral VSF protein and a method for prevention or treatment of viral infections in USA [11] Updated 07 Sep 2018 |
| 14 Apr 2005 | Patent Information | ImmuneMed has patents pending for pharmaceutical composition of an anti-viral VSF protein and a method for prevention or treatment of viral infections in USA [12] Updated 07 Sep 2018 |
| 17 Mar 2004 | Patent Information | ImmuneMed has patent protection for pharmaceutical composition of an anti-viral VSF protein and a method for prevention or treatment of viral infections in South Korea Updated 07 Sep 2018 |
| 07 Aug 2003 | Patent Information | ImmuneMed has patents pending for pharmaceutical composition of an anti-viral VSF protein and a method for prevention or treatment of viral infections in World [13] Updated 07 Sep 2018 |
References
-
Lonza Signs Applied Protein Services Agreement with ImmuneMed for Immunogenicity Risk Assessment and Deimmunization of Novel Protein.
Media Release -
A Multi Center, Randomized, Double-blind, Parallel Design, Phase 2 Study to Evaluate the Efficacy and Safety of hzVSFv13 Compared to Standard of Care After Intravenous(IV) Administration With Add-on Standard of Care in COVID-19 Moderate to Severe Patients
ctiprofile -
A Multi Center, Randomized, Double-blind, Parallel Design, Phase 2 Study to Evaluate the Efficacy and Safety of hzVSFv13 Compared to Standard of Care After Intravenous (IV) Administration With Add-on Standard of Care in COVID-19 Moderate to Severe Patients
ctiprofile -
ImmuneMed's hzVSF-v13, COVID-19 clinical trials accelerate development of the treatment.
Media Release -
Efficacy and Safety of Intravenously Administered hzVSF-v13 in Patients With COVID-19 Pneumonia: a Phase II, Proof of Concept, Multicentre, Randomized, Parallel-group, Double-blind, Placebo-controlled Study
ctiprofile -
ImmuneMed's 'hzVSF,' Used for Treatment of COVID-19 Pneumonia Patients.
Media Release -
A Phase IIa Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Oral Antiviral Agents/hzVSF-v13 Combination Therapy vs Oral Antiviral Monotherapy in Chronic Hepatitis B Patients
ctiprofile -
hzVSF-v13 - A Phase I, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Investigate Safety, Tolerability and Pharmacokinetics After Intravenous and Subcutaneous Administration in Healthy Adults
ctiprofile -
Dose Blocked-randomized, Double-blind, Placebo Controlled, Single Dose, Dose-escalation Study to Investigate the Safety, Tolerability, Pharmacokinetic Characteristics of hzVSF-v13 After Intravenous Administration in Healthy Male Volunteers
ctiprofile -
ImmuneMed discovers endogenous broad-spectrum antiviral drug candidate. Internet-Doc 2017;.
Available from: URL: https://assets.zapnito.com/users/42377/documents/17485/ImmuneMed%20June%202017.pdf -
US7514082B2. Internet-Doc 2021;.
Available from: URL: https://patents.google.com/patent/US7514082B2/en -
US20050080236A1. Internet-Doc 2021;.
Available from: URL: https://patents.google.com/patent/US20050080236A1/en -
WO2003064461A1. Internet-Doc 2021;.
Available from: URL: https://patents.google.com/patent/WO2003064461A1/zh
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