[Ip-health] Do Pharmaceutical Firms Invest More Heavily in Countries with Data Exclusivity?"

Biotech. Info. Inst. biotech at biopharma.com
Sun May 12 09:30:59 PDT 2013


I should add that my analysis of marketed U.S. biopharmaceutical product patent expirations was a 'best case' type analysis (in the context of this group surely favoring early patent expiration; worst-case for industry), in the sense that I used the earliest among likely patent expiration dates.  But in the real world, we all know innovator/reference product companies are going to file suit against initial biosimilar competitors using every potentially-applicable patent they have received and licensed.  

Thus, the data I reported the other day showing U.S. patent protection for marketed biopharmaceuticals almost always exceeding any approvals-conferred exclusivities would be even more dramatic, have shown even less relevance of market and data exclusivity (perhaps, even zero), if I had not simply used the earliest among likely patent expiration dates. 

With biopharmaceuticals, retrieving relevant patents and determining their relevance to products and their manufacture is difficult and ultimately subjective.  With many, probably most, products, I actually report multiple possible dates (patents) and/or range.  But for purposes of calculating the product's patent expiration (the data I reported), I select the single likely earliest date.  For example, below is my patent expiration full text/annotation field for Humira (the no. 1-selling biopharmaceutical), with me here adopting 2016 for my study (comparisons with orphan market and data exclusivities):

U.S. patent 6,090,382,"Human antibodies that bind human TNF-alpha," and others in its family, including 6,258,562 and 7,223,394, have a calculated expiration date in 2016.  Abbott in an “Information Statement” filed with the Securities and Exchange Commission (SEC) reported that the US composition of matter patent for Humira is expected to expire in Dec. 2016. Various discussions of the spin-off of Abbvie from Abbott cite expiration in 2016.

US 7,223,394, "Human antibodies that bind human TNF?," assigned to Abbott, with some rather specific claims (that may or may not apply to Humira) has a calculated expiration date of March 16, 2019.  

2018, if Cabilly III (broad recombinant mAb patent held by Genentech/Roche) was licensed by Abbott with indications- or TNF mAb class-based exclusivity [which has not been publicly reported]

US 7,070,775, "Recombinant A2-specific TNF specific antibodies." assigned to Centocor/Johnson & Johnson and New York University, with Abbott found guilty of violating this patent and having to pay about $1.8 billion in penalties (showing strong patent and ownership by J&J), had a calculated expiration date of March 18, 2011.

Thomson Reuters has reported U.S. patent expiration in 2016.  ABN Ambro has reported U.S. expiration in 2013.  Tech. Catalysts Intl., affiliated with Harvest Moon Pharmaceuticals, has reported U.S. patent expiration in 2017.  

Compared to many products, this is a relatively simple patent analysis, with many involving more patents and uncertainties.  With Humira, I went with 2016, but that does not mean that Abbott will not bring suit against biosimilar candidates using 7,223,494; if Abbott has or decides to exclusively license Cabilly III from Roche, that could extend coverage to late 2018; etc.

I know my findings are not at all welcome news for most list members, with shorter or even no patent protection preferred, and with shortening data exclusivity seemingly a simple way to enable earlier biosimilar market entry.  If anyone has contrary data or is interested in using my data in their own or collaborative studies, please contact me.  

Thank you.

Ronald A. Rader
President / Author & Publisher of BIOPHARMA:  Biopharmaceutical Products in the U.S. and European Markets
Biotechnology Information Institute
1700 Rockville Pike, Suite 400
Rockville, MD 20852
Phone:  301-424-0255
E-mail:  biotech at biopharma.com
Web sites:  www.biopharma.com; www.bioinfo.com; 
    www.biosimilars.com; www.biopharmacopeia.com




On May 10, 2013, at 10:11 AM, Biotech. Info. Inst. wrote:

> I don't have much time now, but to hit some major points:
> 
> My analysis only concerns comparing patent vs. regulatory approval-conferred exclusivity expirations for U.S. marketed biologics/biopharmaceutical products.  I evaluated relevant patents (identified using my BIOPHARMA database at www.biopharma.com), often did some updating or confirmatory patent searching, calculated related patent expirations, and then calculated potential orphan (7 years from approval) and granted data exclusivity (12 years from approval), and compared the dates.  This was done for 119 currently-approved biologics (excluding vaccines and blood products), with ≥90% of these being recombinant proteins/antibodies, obviously including those products with any significant markets.  In fact, all or nearly all of these 119 products have one or more biosimilar/biobetter versions reported as in development (derived from the most extensive biosimilars/biobetters pipeline database, which I will be launching soon; see www.biosimilars.com, left side).  For comparison, there are ≥140 recombinant proteins currently approved in the U.S.  The core data are shown in the following figure:
> 
> Table 1:  Percent of Reference Products with Patents Expiring After Market and Data Exclusivities Expirations
> Patents Expire After
> 
> U.S.
> 
> EU
> 
> Data exclusivity
> 
> 87% (12 yr.)
> 
> 86% (10 yr.)
> 
> Orphan exclusivity
> 
> 96% (7 yr.)
> 
> 96% (10 yr.)
> 
> 
> Regarding how many products evaluated have ≤10 years U.S. patent protection post-approval, it looks to be 15 out of 119 or 12.6%.  Also, the above chart shows that European patents expire after 10 years EU orphan and data exclusivities with 96% of products evaluated. 
> 
> Yes, from my analyses, all the effort put in, by both industry and activists, made over biologics data exclusivity in the context of BPCIA legislation was a waste.  I welcome receiving information about any U.S. biopharmaceutical products where relevant patents expire before approvals-conferred exclusivities.  
> 
> A major reason why I may be reporting longer patent protection than others is that I believe my patent analysis has been done in more depth than other published studies.  Besides starting out with more extensive patent information (from BIOPHARMA), similar studies have mostly simplistically concentrated on just the composition-of-matter (sequence)-type patents and ignored:  other types of patents (use/indications, formulation, bioprocessing, reference standards, etc.); exclusively licensed patents (just as important as company-assigned patents); and patent extensions.  
> 
> I hope to provide more information this weekend.
> 
> Thank you for your interest.
> 
> Ronald A. Rader
> President / Author & Publisher of BIOPHARMA:  Biopharmaceutical Products in the U.S. and European Markets
> Biotechnology Information Institute
> 1700 Rockville Pike, Suite 400
> Rockville, MD 20852
> Phone:  301-424-0255
> E-mail:  biotech at biopharma.com
> Web sites:  www.biopharma.com; www.bioinfo.com; 
>     www.biosimilars.com; www.biopharmacopeia.com
> 
> 
> 
> 
> On May 10, 2013, at 7:23 AM, Jamie Love wrote:
> 
>> I agree with Brook's comments about the importance of test data
>> exclusivity as regards developing countries with different patent
>> landscapes, and thank Michael for addressing an important policy issue
>> of particular relevance to developing countries.
>> 
>> It is also true that BIO and PhRMA have gone to the wall in the US
>> legislative battles to get 12 rather than 7 years of test data
>> protection for biologic drugs. Were the companies spending their
>> political capital for an issue that was unimportant in practice?
>> 
>> These are a few additional comments and questions.
>> 
>> It is more difficult to understand the patent terms for biologic
>> drugs, because we don't yet have a good biosimilar pathway, and we
>> also don't have Orange Book patent disclosures.
>> 
>> The first drug that I worked on was Taxol, the cancer drug, which had
>> zero patent protection when first registered, and test data was the
>> only barrier for generic competition.  It is true that for small
>> molecule drugs, with only a bioequivalence standard for generic entry,
>> few NMEs have term terms less than 5 years of patent protection, but
>> it does happen, on drugs that are expense because of the test data
>> barrier to entry.  I imagine it happens more frequently the longer the
>> term of the test data protection.
>> 
>> For Ronald Rader, you say that the mean period of patent protection
>> for drugs is 15.3 years. That number seems roughly consistent with
>> some earlier work that Michael Palemdo and I did looking at the period
>> of time before a drug has one or more competitor.   Can you tell us
>> more about your sample?  Is this all NMEs?  All small molecule drugs?
>> Does it include or exclude NDAs that involve fixed dose combinations
>> or new formulations of drugs?   Also, can you tell us how many drugs
>> have less than 10 years of patent protection (as opposed to 7)?
>> Between 7 years and 12 years, there are probably more cases where the
>> test data would become relevant.
>> 
>> 
>> On Thu, May 9, 2013 at 12:49 PM, Biotech. Info. Inst.
>> <biotech at biopharma.com> wrote:
>>> Yes, the 2013 administration budget proposal cites $4 billion in savings over 10 years for federal pharmaceutical expenditures from shortening U.S. data exclusivity from 12 to 10 years.  $.4 billion/year is not all that much considering over 100 current products with a current U.S. market about $60 billion, including >40 current blockbusters (>$1 billion/year worldwide revenue), will be coming off-patent with biosimilars entering the U.S. market by the end of the decade.  If  $400 million/year savings is spread out over just 20 products affected by this data exclusivity change, that's a an average savings of $20 million/year/product.  In this context, the $4 billion/decade savings could even be low.
>>> 
>>> But my data shows that patents almost always determine U.S. biosimilar marketability.  So where does this study come up with any savings from shortening the U.S. data exclusivity period?  It would be interesting to know what products data exclusivity shortening promoters and lobbyists presume would get into the market sooner, if U.S. data exclusivity were shortened, and how patent expirations were calculated.  As with nearly all biosimilar-related patent expiration studies, did the one used simplistically just look at composition-of-matter (sequence) patents, and as I've reported concerning nearly all such published data, ignore:  patent extensions; licensed patents, particularly exclusively exclusively licensed patents; and other types of patents, including key use/indications, bioprocessing, formulation, reference standards, etc. patents (as my analysis included)?  I suspect so, since essentially all published data have ignored these aspects.
>>> 
>>> To address the question posed by the subject of this thread:  At least in the U.S. and with biopharmaceuticals, I expect data exclusivity to not have any significant impact.  In fact, it is rather irrelevant.  I realize that this is not welcome news for most members of this list, and I welcome learning of conflicting studies.
>>> 
>>> Thank you.
>>> 
>>> Ronald A. Rader
>>> President
>>> Biotechnology Information Institute this
>>> 1700 Rockville Pike, Suite 400
>>> Rockville, MD 20852
>>> Phone:  301-424-0255
>>> E-mail:  biotech at biopharma.com
>>> 
>>> 
>>> On May 9, 2013, at 10:42 AM, Michael Palmedo wrote:
>>> 
>>>> Thanks for your comment.
>>>> 
>>>> The paper wasn’t really written about whether or not biologics in the U.S. should have 12 or 7 or X years of data exclusivity.  It says that Member countries of the WTO have a range of options for data protection;  data exclusivity has been shown to raise prices (see Oxfam and Shaffer and Brenner); and the relationship between whether or not a country has data exclusivity and the level pharmaceutical investment is uncertain at best.
>>>> 
>>>> That said, the Obama Administration certainly thinks that less data exclusivity for biologics will lead to greater access to generics/FOBs.  As you know, the 2013 budget proposalpredicts that reducing the term of exclusivity will "will result in $4 billion in savings over 10 years to Federal health programs including Medicare and Medicaid.”  A footnote would have been nice… any idea where the number comes from?
>>>> 
>>>> Mike
>>>> 
>>>> 
>>>> From: Biotech. Info. Inst. [mailto:biotech at biopharma.com]
>>>> Sent: Wednesday, May 08, 2013 3:05 PM
>>>> To: Michael Palmedo
>>>> Cc: Ronald A. Rader; ip-health
>>>> Subject: Re: [Ip-health] Do Pharmaceutical Firms Invest More Heavily in Countries with Data Exclusivity?"
>>>> 
>>>> Regarding data exclusivity, I've recently evaluated the patent, market and data exclusivities in the U.S. and EU for 119, essentially all, currently-approved potential reference biologics/biopharmaceuticals (ignoring vaccines and blood products; >90% recombinant proteins/antibodies), and calculated biosimilar and biobetter launchability in these major markets.  [See www.biosimilars.com, left side; with patent and exclusivities data already included in the BIOPHARMA database (www.biopharma.com)].  I found that patent expiration exceeds the regulatory-granted exclusivities with 87% of products in the U.S. and 86% in the EU.  The average length for patent protection after initial approval was 15.3 years in the U.S.  Patent coverage exceeds market (orphan) exclusivity, 7 years in U.S. and 10 in EU, with 96% of products in both the U.S. and EU.
>>>> 
>>>> Bottom Line:  Patents are what really matters in terms of follow-on biopharmaceutical marketability in the U.S. and EU.  Regulatory-granted market and data exclusivities are essentially totally irrelevant.  Shortening U.S. data exclusivity for biologics, with proposals for this recurring periodically, would be useless in terms of getting follow-on biologics on the market  sooner.
>>>> 
>>>> Does anyone still believe that shortening data exclusivity for U.S. biologics will have any affect on U.S. biosimilars marketability?  Are there any studies, either pre-BPCIA that have withstood peer review or more recent, showing that shortening U.S data exclusivity would accelerate access to biosimilars?
>>>> 
>>>> For those interested in the biosimilars development pipeline and likely evolution of the U.S. market, watch for an article on these topics I authored to be published in the June issue of BioProcess International (journal and articles free online).  Most members of this list will likely be encouraged by my asserting that the U.S. biosimilars market will be more like that of generic drugs, with lots of competition, likely >10-12 biosimilars for most current major (blockbuster) products, with prices significantly lower than the wimpy 20%-30% at best currently projected for U.S. biosimilars.
>>>> 
>>>> Thank you.
>>>> 
>>>> Ronald A. Rader
>>>> President / Author & Publisher of BIOPHARMA:  Biopharmaceutical Products in the U.S. and European Markets
>>>> Biotechnology Information Institute
>>>> 1700 Rockville Pike, Suite 400
>>>> Rockville, MD 20852
>>>> Phone:  301-424-0255
>>>> E-mail:  biotech at biopharma.com
>>>> Web sites:  www.biopharma.com; www.bioinfo.com;
>>>>    www.biosimilars.com; www.biopharmacopeia.com
>>>> 
>>>> 
>>>> On May 8, 2013, at 10:45 AM, Michael Palmedo wrote:
>>>> 
>>>> 
>>>> Hello all.
>>>> 
>>>> 
>>>> 
>>>> I wanted to share my paper "Do Pharmaceutical Firms Invest More Heavily
>>>> in Countries with Data Exclusivity?" which will be coming out in
>>>> Currents International Trade Law Journal this summer.
>>>> 
>>>> 
>>>> 
>>>> Abstract:     Countries may choose various methods of data protection in
>>>> order to comply with the TRIPS Agreement. Policymakers should consider
>>>> the effects of data exclusivity on prices and investment relative to
>>>> other types of data protection. The data presented here suggest there is
>>>> no relationship between whether or not a country has data exclusivity,
>>>> and the amount of investment in the country by the pharmaceutical
>>>> industry. On the other hand, empirical evidence in previous papers has
>>>> shown that data exclusivity does drive prices higher.
>>>> 
>>>> 
>>>> 
>>>> Full paper: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=2259797
>>>> 
>>>> 
>>>> 
>>>> Mike
>>>> 
>>>> 
>>>> 
>>>> --
>>>> 
>>>> Mike Palmedo
>>>> 
>>>> Program on Information Justice and Intellectual Property
>>>> 
>>>> American University Washington College of Law
>>>> 
>>>> 4801 Massachusetts Ave., NW, Washington, D.C. 20016
>>>> 
>>>> W: 202-274-4442 | M: 571-289-3683
>>>> 
>>>> wcl.ameican.edu | infojustice.org | pijip-impact.org
>>>> 
>>>> 
>>>> 
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>>> 
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>> 
>> 
>> 
>> -- 
>> James Love.  Knowledge Ecology International
>> http://www.keionline.org, +1.202.332.2670, US Mobile: +1.202.361.3040,
>> Geneva Mobile: +41.76.413.6584, efax: +1.888.245.3140.
>> twitter.com/jamie_love
> 




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