Patent•
Anti-opioid vaccines
16 May 2019-
TL;DR: In this paper, the authors present a method for producing immunoconjugates of oxycodone and hydrocodone suitable for raising antibodies in animals specific for the opioid drugs. But the method is not suitable for humans.
Abstract: The invention provides haptens and methods of preparation thereof, for producing immunoconjugates of oxycodone and hydrocodone suitable for raising antibodies in animals specific for the opioid drugs. Adminislration of the opioid-speeific antibodies to humans having the opioid drugs in a body fluid such as blood serum, binds the opioid drugs to the antibody, making the opioids unavailable for producing a drug effect. Accordingly the antibodies can be used to reverse the effects of a drug overdose of oxycodone and hydrocodone, or to reverse a perceived mental effect of the. drugs, such as euphoria.
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Patent•
10 Dec 2020
TL;DR: In this paper, the authors describe methods of making monoclonal antibodies and methods of using those antibodies to treat a subject with an opioid use disorder or neonatal opioid withdrawal syndrome or preventing and reversing opioid overdose in a subject.
Abstract: This disclosure describes opioid-specific monoclonal antibodies (mAb), methods of making those antibodies, and methods of using those antibodies. The methods include, for example, treating a subject with an opioid use disorder or neonatal opioid withdrawal syndrome or preventing and reversing opioid overdose in a subject. Additionally or alternatively, the antibodies may be used to detect opioids including, for example, in a screening, diagnostic, or forensic assay.
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TL;DR: Both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten, demonstrating the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity.
Abstract: Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.
113 citations
TL;DR: In rats given a single intravenous dose of OXY, immunization with OXY(Gly)4-KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain.
Abstract: Opioid conjugate vaccines have shown promise in attenuating the behavioral effects of heroin or morphine in animals. The goal of this study was to extend this approach to oxycodone (OXY), a commonly abused prescription opioid. Haptens were generated by adding tetraglycine (Gly)4 or hemisuccinate (HS) linkers at the 6-position of OXY. Immunization of rats with OXY(Gly)4 conjugated to the carrier proteins bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) produced high-titer antibodies to OXY and its metabolite oxymorphone with substantially lower affinities for other structurally related opioid agonists and antagonists. There was no measurable binding of antibody by the (Gly)4 linker alone or off-target opioids methadone and buprenorphine. OXY(HS) conjugates were less immunogenic despite achieving protein haptenation ratios comparable to OXY(Gly)4-BSA. In rats given a single intravenous dose of OXY, immunization with OXY(Gly)4-KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain. Vaccine efficacy correlated with serum antibody titers, and it was greatest in rats given the lowest OXY dose (0.05 mg/kg) but was significant even after a larger OXY dose (0.5 mg/kg), equivalent to the high end of the therapeutic range in humans. These effects of OXY(Gly)4-KLH on drug disposition were comparable to those of nicotine or cocaine vaccines that are in clinical trials as addiction treatments. Immunization with OXY(Gly)4-KLH also reduced OXY analgesia in a thermal nociception test. These data support further study of vaccination with the OXY(Gly)4-KLH immunogen as a potential treatment option for OXY abuse or addiction.
76 citations
Patent•
30 Sep 1997
TL;DR: In this paper, the hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo by administering, in a therapeutic composition, are disclosed.
Abstract: Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo by administering, in a therapeutic composition, are disclosed. Methods of preparing said conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.
72 citations
TL;DR: The preparation of two active PO vaccines are described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design and resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.
Abstract: Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.
37 citations
Patent•
20 Dec 2002TL;DR: Novel haptens which can be conjugated to form immunogens, are of formula I, II or III wherein R is a divalent alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, and X is a functional group as discussed by the authors.
Abstract: Novel haptens, which can be conjugated to form immunogens, are of formula I, II or III wherein R is a divalent alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, and X is a functional group.
7 citations