Theme 7 Lectures Summarised Flashcards
Why is it crucial to file a patent once a series of interesting compounds are identified?
Patent protection allows exclusive benefits from an invention for a fixed time, typically 20 years, as a trade-off for disclosing the invention to the public
s,d,c,uniq
What are the key components of a patent?
Scope, description, and claims, with claims being crucial as they detail the invention’s unique components.
drafting and filing 6
What are the estimated costs of patenting an invention?
The costs can range from initial drafting and filing to international search reports and translations, potentially totaling around £75,000 over 6-7 years
background,invent,dd, worked examples
What constitutes the anatomy of a patent in drug development?
- Introduction (technical field and background)
- Statement of invention (restates the main patent claims i.e., what it is and does).
- Detailed description (including fall-back claims and how to carry out invention).
- Worked examples - preparations and experiments which have been carried out.
- Claims - define the invention and define what the patent should achieve. Usually 1 broad generalised claim backed up by some narrower claims.
per se,1/2,salts,
What are the different types of patent claims?
Composition of matter claim/compounds per se - If a compound has never been described before it is possible to claim the compound (per se) and compounds similar to it. This claim will cover the compound in any setting, in any form and for any use.
First medical use claim- if compound is known but not for medical use.
Second medical use claim - if compound has a medical use but not for the one in the patent.
Salt/crystalline form claim- entitles them to all physical forms of a compound if they display beneficial effects.
Composition of claims and contributions- a combination of the compound with particular excipients or other compounds.
Dosage regimen claim
Synthetic processes claim- improved methods of preparing the compound.Claims can include compounds per se, first and second medical use claims, claims for new physical forms like salts or crystalline structures, dose regimen and synthetic processes.
claims and intellectual
What can be learned from the patent case study of Atorvastatin?
Atorvastatin’s patent exemplifies the value and structure of claims in protecting the intellectual property of pharmaceuticals
Broad claims between Phar amd MERK
Why should the scope of patent claims be carefully considered?
Broad claims can be vulnerable to validity challenges, as seen in the litigation between Pharmacia and Merck over COX-II inhibitors
Why is timing considered?
It is important to file a patent early in the discovery process if there is heavy competition in the area to prevent the idea being stolen. However, patents only last 20 years from filing, so by the time the drug comes comes to market and starts generating income, there may only be 7 years or so of exclusive profit left before competitors can produce the drug under a different/generic name and profit from it.
What is more important, the examples or the claims?
Remember, it is not the examples the determine what is protected by a patent
IT IS THE CLAIMS
Searle and MERCK,(XYR1R2),Broad
How did the broadness of Searle’s patent claim for Celecoxib both benefit and hinder it?
Celecoxib by Searle and Rofecoxib by Merck were 2 selective COX-II inhibitors which were developed around the same time.
Searle sued Merck as in Searle’s patent, claim 1 was for a structure containing an X, Y, R1 and R2 of certain listed functional groups, one of which covered structure which possessed a tautomerised structure of Rofecoxib. They won this claim.
However, since the claim was so broad (due to the extensive listed options for the X, Y, R1 and R2 groups), some of the compounds claimed didn’t have selective COX II inhibitory activity, or any COX inhibitory activity at all. Therefore, Merck filed a countercase stating that since not all the compounds listed were inactive, the patent did not contain an inventive step. The judged granted for the patent to be revoked.
PPB,spm,buffer
Describe the equilibrium dialysis assay.
This in vitro assay measures the level of plasma protein binding of a drug.
A known concentration of drug is put in a semi-permeable compartment containing plasma and albumin (or other plasma protein). This compartment is placed in a buffer, and the free drug moves from down its concentration gradient from the plasma to the buffer, while bound drug remains in the compartment. The concentration in the buffer indicates the proportion of free drug.
pglyco eflux
Why is the mu-opioid agonist loperamide used as an anti-diarrhoea agent and not an opioid analgesic?
Morphine and other opioids penetrates the blood brain barrier and acts on mu-opioid receptors in the brain to reduce pain signal transmission.
Loperamide is rapidly transported out of the brain by P-glycoprotein efflux transporters in the brain, preventing it from acting there.
Instead it acts on enteric mu-opioid receptors, resulting in reduced gastric motility and increased fluid reabsorption, and therefore constipation (side effect of opioids). This can be used to treat diarrhoea with minimal side effects.
What is toxicity through mechanism-based pharmacology?
When activation of the target causes unwanted effects as well as the desired therapeutic effect.
Why are electrophiles not desired in drug or metabolite structures?
Nucleophilic attack of electrophiles by nucleophiles in the body (e.g., in proteins or DNA) result in the electrophiles becoming covalently bound which can lead to toxic effects, most commonly hepatoxicity (liver) and genotoxicity (DNA).
CY1A2, CONJ,LOSS,COV,CANCER
How does the aniline functional group cause mutagenicity?
- Aniline oxidised by CYP1A2 to aryl hydroxylamine.
- Aryl hydroxylamine undergoes conjugation via a range of transferases.
- Products of conjugation undergo acid catalysed loss of either acetic acid, water, or sulphate to generate a highly electrophilic nitrenium ion (Ar-NH+).
- Species forms covalent adducts with DNA guanines.
- Persistent mutations caused by intercalation of adducts in hotspots of DNA can lead to frameshift mutations in these hotspots, ultimately leading to cancer.
