Renovo's expertise and experience in cocrystal research, combined with industry leading cocrystal screening and characterization abilities positions Renovo as the leading authority on the application of cocrystal technology to pharmaceuticals. Renovo is uniquely positioned to effectively screen and identify cocrystals as well as scale up, characterize and ascertain the utility of cocrystal systems.
At Renovo we consider salts and cocrystals to be a connected continuum of multi-component crystals. A significant portion of our contract work is performing salt screens using the same techniques that were developed for cocrystals. With the high prevalence of weakly basic APIs, we have found that combining salt and cocrystal screening into a unified process is more effective and efficient. Ask Renovo how we can extend and improve your salt screening.
An often overlooked area is polymorph screening of cocrystals. If a cocrystal is selected as the development form the FDA will want to see a polymorph study on the cocrystal. Renovo's expertise in cocrystal screening is applied equally well to cocrystal and salt polymorph studies.
While multi-component crystalline solids such as salts and cocrystals are the area of focus at Renovo, polymorph screens on single-component solids are often performed in parallel with salt or cocrytsal screens.
After a commercially relevant multi-component material has been identified, Renovo can provide the support needed to scale up production. Renovo can work with you and your CMO to identify a suitable crystallization process, construct the relevant phase diagrams, and deliver batches up to multi-liter reactor scale.
Finding and characterizing a cocrystal is just the first step. We know how to leverage cocrystal physical properties to create effective dosage forms.
One of the most useful properties of cocrystals of poorly soluble non-ionizable drugs is the ability to rapidly saturate. However, one of the biggest obstacles to effectively harnessing a cocrystal’s potential is formulating it in a way that doesn’t allow the API to immediately precipitate once the cocrystal has dissolved. Renovo has performed extensive R&D in this area in order to create supersaturating cocrystal formulations.
Renovo can assist with your cocrystal IP needs, including "finding all of the forms" and providing patent drafting support. Cocrystals also present a tremendous opportunity to create improved products as part of a life cycle management strategy using the 505(b)(2) filing route.
Renovo didn’t just adopt the cocrystal screening and characterization methods from the literature like most of the CRO’s that are advertising cocrystal screening services. We developed and published those methods, and we have continued to push the boundaries of the field. We have performed cocrystal screens on over 250 APIs to date and that experience cannot be found anywhere else.
Selection of the optimal physical form of an API is a critical part of the drug development process. Most drugs are administered as solids or are solids at some point of the drug manufacturing process. The solid state properties can significantly affect the efficacy and the manufacturing process of the drug product. Crystalline materials are the most preferred solid form and efforts to obtain crystalline API forms are an important goal during drug development.
In early phases of the drug development cycle, cocrystal screening is performed if polymorphs, hydrates or salts do not have appropriate physical properties. Cocrystals are especially useful if the API is non-ionizable and unable to form salts as polymorphs and hydrates would otherwise be the only crystalline form options available. In later stages of development more extensive cocrystal screening is performed to identify and patent all relevant solid forms of a drug molecule.
The Renovo cocrystal screening process is modular and flexible. Renovo will tailor the screening approach to the unique properties and goals of each API. Several different levels of screening are available depending on the project requirements. Screening project turn-around times average 4 to 6 weeks.
Renovo's cocrystal screening methods have proven to be very effective. For example, for one partner company Renovo screened 32 molecules for cocrystals and identified a cocrystal for 75% of the molecules screened. We have also been able to compare Renovo screening results with the screening results from other pharmaceutical research groups and CRO’s and in all cases the Renovo process found the same or additional cocrystals. The cocrystal screening process at Renovo is effective, efficient, reproducible and fast.
Renovo can provide a quote for your project that will specify the price, timeline, material requirements, and deliverables. If your project requires a confidentiality agreement in order to discuss the details necessary to generate a quote, Renovo can provide a template of a two-way NDA (non-disclosure agreement), also known as a confidentiality agreement (CA) or confidential disclosure agreement (CDA) or you can send your standard NDA to Renovo. Once a NDA is in place we can discuss your project details and pricing.
Our definition of a potent compound: A compound with an Occupational Exposure Limit (OEL) of approximately 1 – 10 μg/m³ (8h TWA). These specifications are also consistent with SafeBridge Level 3 and/or OEB Band 4 (on a 5 band table) or OEB Band 3 (on a 4 band table) designations.
Renovo does not work with 'highly potent' compounds that have an OEL below ~1 μg/m³ (8h TWA).
The properties of cocrystals, specifically the solubility and dissolution rate, are often dramatically different from the existing forms of the API. For example, many cocrystals of poorly soluble drugs can dissolve almost instantly and reach saturation levels. This behavior can be leveraged to create not only product improvements but also additional patent protection and market exclusivity for the product.
The improvements to the product should be directly tied to the physical properties of the cocrystal in order to maintain exclusivity based on a cocrystal. If the benefits afforded by the cocrystal can be duplicated in other ways, for example through advanced formulation, then the cocrystal patent protection could be vulnerable to a circumvention strategy.
An effective way of maintaining market exclusivity is to find and patent all of the solid forms and then use a solid form in the drug product that has patent protection beyond the expiration of the molecule patent. However, this strategy is vulnerable to generic products that use a clever formulation or alternative dosage form to circumvent your solid form patents. Additional protection can be gained by using a solid form whose properties are closely tied to the performance of the drug product.
For cocrystal based products, the properties of the cocrystal should be tied to the improved performance of the drug in order to maximize the potential of extending exclusivity based on the cocrystal solid form patent. If the enhancement cannot be easily duplicated with a non-infringing form then it will be difficult to circumvent the cocrystal patent.
Here is something that is becoming more assured every day for drugs that make it to market: If you don’t find and patent cocrystals (and salts, polymorphs and hydrates) of your API, someone else will. This could result in lost LCM opportunities or worse – a shorter exclusivity period.
Renovo can help you determine the potential of your API to form cocrystals and assist you in balancing the risks vs. the expense of performing a cocrystal screen in order to secure the IP on your API.
If a drug product uses a patent protected API polymorph to extend market exclusivity beyond the expiration of the original molecule patent, a traditional ANDA generic application, a.k.a. 505(j), would require the use of that patented polymorph in the bioequivalent generic product. However, if a cocrystal can be used to make a bioequivalent formulation, then this new product can be filed under the 505(b)(2) route and it should receive an AB rating as a bioequivalent product and not infringe on the polymorphic form patent protecting the reference drug product.