Anavex Life Sciences Corp (AVXL)

[orveko_inc]

What I don't understand is why Anavex never went after a method of use patent targeting AD with 2-73 alone. Was that not possible according to some issue with patent law? I've tried to read the abandoned patent application and the multiple claims submissions and corrections prior to abandonment and it looks more like a first attempt at the current melanoma patent than a simple method of use for AD using 2-73.

In short, I don't think they can.

In not-so-short:

U.S. application 12/522761 was filed in July of 2009 and based on Greek patent 1005865, filed in 2007. It covered, quite broadly, a method of using A2-73 as a pharmaceutical product with neuroprotective, anti-depressive, anticonvulsive, anti-cancer, anti-metastatic, and anti-inflammatory activity.

This application received a final rejection, was abandoned, was resubmitted in February of 2013 as 13/777471, and as of today, remains unpublished. I believe the problem here is Greek patent 1002616, filed in 1996. One of the claims covered the use of A2-73 "for the preparation of pharmaceuticals with anticonvulsant, antidepressive and nootropic activity." Thus, claims in 12/522761 that relate to neuroprotective, anti-depressive, and anticonvulsive activity were anticipated by Greek patent 1002616. Even if they went straight to the point and stated Alzheimer's, they'd get caught in the net cast by Greek patent 1002616. Regarding claims related to anti-cancer, anti-metastatic, and anti-inflammatory activity, the USPTO stated “a chemical composition and its properties are inseparable. Therefore, if the prior art [Greek patent 1002616] teaches the identical chemical structure, the properties applicant discloses and/or claims [in 12/522761] are necessarily present.” In other words, even though the original Greek patent does not mention anti-cancer, anti-metastatic, and anti-inflammatory activity, these properties must be present because the compound is present.

U.S. application 13/201271 was filed in August of 2011 and based on Greek patent 1006794, filed in 2009. It covered the composition and method of using A2-73 in combination with Quinacrine, Methylene blue, or Astemizole as pharmaceutical products with anti-cancer, anti-metastatic, anti-viral, cytoprotective, anti-inflammatory pain, and anti-neuropathic pain activity.

This application received a final rejection, was abandoned, was resubmitted in March 2014 as 14/205637, and eventually was allowed as a patent in November 2015. The final claims cover the composition and method of using A2-73 in combination with Quinacrine, Methylene blue, or Astemizole as pharmaceutical products for the treatment of melanoma. The difference here is that A2-73 is being combined with something else.

Enter applications 13/940352 (filed July 2013) and 14/395581 (filed October 2014), both based on Greek patent 1008233, filed in 2013. Both cover the composition and method of using A2-73 in combination with Donepezil, Rivastigmine, Galantamine, and/or Memantine (13/940352 only) as pharmaceutical products for the treatment of Alzheimer’s. These applications are currently being examined, with some difficulty.

More recently, applications 14/865862 (filed September 2015) and 15/194792 (filed ???) were submitted based on 14/395581. 15/194792 isn’t published yet, so not much is known, but 14/865862 claims a method of using A19-144 (the metabolite of A2-73) as a pharmaceutical product for the treatment of Alzheimer’s, Huntington’s, Parkinson’s, depression, and brain ischemia. Additionally, the application claims the composition and method of using A19-144 in combination with acetylcholinesterase inhibitors (e.g.: Donepezil, Rivastigmine, Galantamine) for the treatment of Alzheimer’s and against the cholinergic adverse effects of acetylcholinesterase inhibitors.

Speculation Warning

It’s interesting that Anavex has recently distanced themselves from “Anavex Plus” (A2-73 + donepezil), after early and rather inconclusive data. Perhaps the company is positioning themselves to “relaunch” Anavex Plus as A19-144 + donepezil. A19-144 is a bit of a sleeper. It’s effectively at the same stage of development as A2-73 (being the metabolite of A2-73). PK/PD data from the ongoing Phase 2a trial will provide valuable information on both A2-73 and A19-144. Perhaps the future of Alzheimer’s and other large indications is A19-144?

Anavex is making both an offensive and defensive move by seeking Orphan Drug Designations for A2-73. This may enable a quicker path to market while providing valuable market exclusivity in lieu of patent protection. If they can bring A2-73 to market with one or more orphan indications while showing promising clinical data for Alzheimer’s or other larger indications, then they will likely see significant off-label use. Now, let’s say Anavex chooses not to do a pivotal Alzheimer’s trial for A2-73 and switches gears to A19-144 instead. This could significantly deter competitors from launching generic versions of A2-73 (unless of course they wanted to conduct their own Alzheimer’s trial, which would be unlikely because there would be zero market protection incentives for them). Anavex could hit the market with A2-73 as an orphan drug, generate sales and interest and then follow up a few years later with A19-144 combination therapies for Alzheimer’s and other larger indications – hopefully with patents in tow.

And then there's A3-71...