Biologics and Biosimilars Bits and Bytes – November 30, 2015

As our BRIC Wall readers are aware, biologics and biosimilars are becoming more newsworthy and noteworthy around the world. To help our readers stay current, we are introducing a new feature – Biologics and Biosimilars Bits and Bytes – to provide periodic updates on the most significant developments. We hope you find this new feature informative.

Amgen Files for First U.S. Approval of a Biosimilar to AbbVie’s Humira®

On November 25, 2015, Amgen filed a 351(k) application with the U.S. Food and Drug Administration (FDA) for ABP 501, a biosimilar version of AbbVie Inc.’s (AbbVie) Humira® (adalimumab). The filing was noteworthy not only because it is believed to be the first biosimilar application filed in the U.S. for adalimumab, but also because it was Amgen’s first submission of any biosimilar application to the FDA.

Adalimumab is a human monoclonal antibody that is used to treat autoimmune diseases. It works by binding to tumor necrosis factor (TNF)-alpha preventing it from activating TNF receptors (which cause the inflammatory reactions associated with autoimmune diseases). Adalimumab has been approved for the treatment of rheumatoid, juvenile idiopathic and psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and ulcerative colitis. In 2014, worldwide sales reached almost $13 billion.

According to Amgen, its submission included analytical, clinical and pharmacokinetic data. Phase 3 comparative efficacy and safety studies were conducted in both moderate-to-severe plaque psoriasis and moderate-to-severe rheumatoid arthritis patients. These studies met their primary endpoints demonstrating clinical equivalence to adalimumab. Additionally, the submission also included data to support the switching of adalimumab patients to ABP 501.

In addition to Amgen, a number of other companies are developing biosimilar versions of adalimumab. These include: Boehringer Ingelheim (for BI695501), Baxalta and Momenta Pharmaceuticals (for M923), Samsung Bioepsis (for SB5) and Oncobiologics (for ONS-3010).

The EMA Recommends the first Enbrel® Biosimilar for Approval In Europe

On January 21, 2015, Samsun Bioepis, a joint venture between Samsun Biologics and Biogen, filed for approval of Benepali™ (etanercept), also known as SB4, by the European Medicine Agency (EMA). On November 19, 2015, the EMA’s Committee for Medicinal Products for Human Use (CHMP), recommended Benepali™ for marketing authorization. If approved, this will bring the first biosimilar of Enbrel® to market in Europe.

Etanercept is a fusion protein that inhibits the activity of tumor necrosis factor alpha. The CHMP recommended Benepali™ for use:

  1. In combination with methotrexate for treatment of moderate to severe rheumatoid arthritis in adults that have an inadequate response to disease-modifying anti-rheumatic drugs, including methotrexate;
  2. Alone in adults intolerant to methotrexate or when continued treatment with methotrexate is not appropriate;
  3. In the treatment of active and progressive psoriatic arthritis in adults who fail to respond to disease-modifying anti-rheumatic drugs;
  4. In the treatment of severe active ankylosing spondylitis in adults who have had an inadequate response to conventional therapy;
  5. In the treatment of severe nonradiographic axial spondyloarthitis with objective signs of inflammation in adults who have had an inadequate response to nonsteroidal anti-inflammatory drugs; and
  6. In plaque psoriasis in adults with moderate to severe psoriasis who fail to respond to, who have a contraindication to, or who are intolerant to other systemic therapy (such as ultraviolet A light, methotrexate, psoralen, ciclosporin, etc.).

The CHMP’s recommendation will now be referred to the European Commission which grants approval for the European Union, Iceland and Norway. Final approval is anticipated by February 2016. Once final approval is received, Benepali™ will be commercialized in Europe and Switzerland by Biogen which also holds the commercialization rights in Japan. Merck & Co. will commercialize in all other markets except the U.S.

This post was written by Lisa Mueller.

TPP and the Continuing Controversy Over the Exclusivity Period for Biologics

This is our third post examining certain of the patent related provisions of the Trans-Pacific Partnership (TPP) from the WikiLeaks released final “agreed version of the TPP chapter on intellectual property rights.”  Our first post, which examined patentable subject matter and grace periods, can be found here.  Our second post, which examined the provisions relating to patent revocation, publication of patent applications and procedures for adjusting patent term due to an unreasonable delay by a patent office, can be found here. In this post, we examine the controversial provisions relating to the exclusivity period for biologics.

The exclusivity period for biologics was one of the major issues that held up the negotiations of the TPP. During the negotiations, the U.S. and Japan favored longer periods of exclusivity (up to 12 years) while Australia and New Zealand favored shorter (up to five years).

What is the difference between data and market exclusivity?

Data exclusivity refers to the period of time following market approval during which a biosimilar manufacturer cannot use the safe and efficacy data (such as preclinical and clinical trial information) of an innovator company. For example, in the U.S., a biosimilar application cannot be submitted to the U.S. Food and Drug Administration (FDA) during the period of data exclusivity (which is four years).

In contrast, market exclusivity refers to the period during which a biosimilar manufacturer cannot be approved for sale; however, a biosimilar manufacturer may use the data of the innovator company for review of its regulatory application. Currently, the U.S. FDA provides eight years of market exclusivity for biologics. The four-year data exclusivity plus the eight-year market exclusivity provides for a total exclusivity period in the U.S. of 12 years.

Article QQ.E.20 of the TPP

The exclusivity period for biologics is provided in Article QQ.E.20 of the TPP which is reproduced below.

Article QQ.E.20: {Biologics}

1. With regard to protecting new biologics, a Party shall either:

(a) with respect to the first marketing approval in a Party of a new pharmaceutical product that is or contains a biologic, provide effective market protection through the implementation of Article QQ.E.16.1 and Article QQ.E.16.3 mutatis mutandis for a period of at least 8 years from the date of first marketing approval of that product in that Party; or alternatively

(b) with respect to the first marketing approval in a Party of a new pharmaceutical product that is or contains a biologic, provide effective market protection:

(i) through the implementation of Articles QQ.E.16.1 and QQ.E.16.3 mutatis mutandis for a period of at least 5 years from the date of first marketing approval of that product in that Party;
(ii) through other measures; and
(iii) recognizing that market circumstances also contribute to effective market protection

to deliver a comparable outcome in the market.

2. For the purposes of this Section, each Party shall apply this provision to, at a minimum, a product that is, or alternatively, contains, a protein produced using biotechnology processes, for use in human beings for the prevention, treatment or cure of a disease or condition.

3. Recognizing that international and domestic regulation of new pharmaceutical products that are or contain a biologic is in a formative stage and that market circumstances may evolve over time, the Parties shall consult after 10 years, or as otherwise decided by the TPP Commission, to review the period of exclusivity provided in paragraph 1 and the scope of application provided in paragraph 2, with a view to providing effective incentives for the development of new pharmaceutical products that are or contain a biologic, as well as with a view to facilitating the timely availability of follow-on biosimilars, and to ensuring that the scope of application remains consistent with international developments regarding approval of additional categories of new pharmaceutical products that are or contain a biologic.

A choice between one of two alternatives

Article QQ.E.20, provides countries with two options for providing a biologics exclusivity period. These options are:

1. A period of at least eight years from the date of first marketing approval; or
2. A period of at least five years from the date of first marketing approval as well as “protection through other measures,” (while recognizing that “recognizing that market circumstances also contribute to effective market protection.”)

Regardless of the option a country chooses, the article is clear that the option selected must provide a “comparable” outcome in the market. Because the article provides varying transition periods for each country, these provisions will come into effect gradually during the next decade. Interestingly, the article also provides that the parties to the agreement will consult after 10 years (unless otherwise decided by the TPP commission), to review the period of exclusivity.

Does the TPP provide data exclusivity, market exclusivity or both?

The provisions of Article QQ.E.16.1 and Article 16.3 as well as Article QQ.E.20, appear to provide only “market” exclusivity for biologics. It is currently unclear whether or not any period of “data” exclusivity can be built into the eight-year period recited under Article QQ.E.20.

Other items of concern

Under the second option, Article QQ.E.20 provides that exclusivity for biologics can be achieved “through other measures.” It is unclear what those provisions might be. In addition, the article also refers to a “comparable outcome in the market.” Given the price tags of biologics, it is hard to see how a three-year difference could result in a comparable outcome.

What has changed?

Not much. Several countries will not have to make any changes to their laws providing biologic exclusivity. For example, the U.S. will not have to shorten its 12-year exclusivity period and Japan and Canada, which each provide eight-years exclusivity, will be able to maintain that number as well. Australia and New Zealand have indicated that their five-year exclusivity periods meet the requirements of the TPP and expect no change. While Mexico did not have any specific legislation providing for data protection for biologics, Mexican courts have been contemplating the possibility of having the period of five years pursuant to NAFTA as the minimum period of protection. Of all the signatories to the TPP, only Brunei currently provides less than five years of exclusivity.

What has the reaction been and where do we go from here?

As with most things, the reaction the TPP in the U.S. depends on who you ask. Both the Biotechnology Industry Organization (BIO) and Pharmaceutical Research and Manufacturers of America (PHARMA) expressed disappointment that the TPP failed to include a 12-year exclusivity period. BIO expressed concern that while the TPP would not impact the 12-year exclusivity period in the U.S., it might “chill global investment” and slow the development of new biologics. Doctors without Borders were far more critical stating that “the TPP will still go down in history as the worst trade agreement for access to medicines in developing countries.”

Hillary Clinton has stated that she believes that pharmaceutical companies got more benefits and consumers fewer. Senator Orrin Hatch (a supporter of the 12-year exclusivity period) has expressed concern that the TPP does not provide enough protection to foster global innovation. On November 20th, House Speaker Paul Ryan expressed concern about the level of intellectual property protection available for biologics in the TPP as well as other aspects of the agreement. Specifically, he stated, “I’m concerned about biologics, quite frankly. There’s other issues I’m concerned about.” He indicated that he believes that Congress can vote on the TPP in 2016 but he is not sure when. Moreover, he stressed that he wants to ensure that the deal meets the objectives set out by Congress in the Trade Promotion Authority (TPA) law. He stated, “Let me back up and say one thing: getting it right matters. This will be the largest trade agreement. It’s 40 percent of gross domestic product. And the goal here, and the reason why we passed TPA is because we need to be writing the rules of the global economy.” Speaker Ryan also made it clear that the TPP should ensure strong IP protections around the world.

Time will tell when and if Congress will vote on the TPP in 2016. Additionally, given that several members of Congress are unhappy with the exclusivity provisions for biologics in the TPP, it will be interesting to see whether or not the Obama administration will have to renegotiate the biologics provisions to ensure greater protection for biologics.

This post was written by Lisa Mueller.

Brazilian Patent and Trademark Office Publishes New Rule on the Prioritization Examination of Patent Applications

On November 10, 2015, the Brazilian Patent and Trademark Office (INPI) published Rule #151 regarding the conditions for requesting priority examination of patent applications. Specifically, Rule #151 revokes Rule #68 of 2013 but maintains many of the previously established conditions. Under the Rule #151 an applicant may request priority examination of a patent application under the following conditions:

  1. An applicant is shown to be at least 60 years old;
  2. A third party is shown to be reproducing the subject matter of the patent application without the applicant’s previous consent;
  3. Promotion funds from promotion agencies or official national credit institutions cannot be obtained unless a patent is granted (provided that such funds have been demonstrated to be an economic subsidy, financing or corporate stake, or otherwise arise from mutual investment funds that will exploit the relevant product or process); and
  4. An applicant is a person with a functional or mental disability or has a severe disease.

Rule #151/2015 revoked the specific provision allowing the Ministry of Health to request prioritized examination of applications involving drugs regularly purchased by the Brazilian Public Health System. The Ministry of Health can still request priority examination of strategic drugs for the Public Health System pursuant to Rule #80/2013.

Furthermore, the Brazilian Government has retained its right to prioritize examination of those applications relevant for national emergency or public interest.

Please watch the BRIC Wall Blog for updates on patent examination in Brazil.

This post was written by Lisa Mueller and Roberto Rodrigues of Licks Attorneys.

Lisa Mueller Featured in Wisconsin Lawyer

Lisa Mueller, author and creator of the BRIC Wall Blog, was featured in Wisconsin Lawyer’s article, “Wisconsin Biotech: A New Frontier for Lawyers,” on November 10, 2015.

In the article, Mueller discusses the importance of her undergraduate career in helping with her legal successes today.

Here is a small excerpt:
Some biotech lawyers hold degrees in the life sciences, which help them understand the nuances of a gene patent or protein manufacturing process. Mueller, a partner at Michael Best & Friedrich, Chicago, and a member of its management committee, received B.S. degrees in chemistry and biology before pursuing her law degree.

“My educational background was a huge help,” says Mueller. “Whether you’re working as a patent or corporate attorney, or doing transactional work and trying to facilitate deals, having an understanding of biotechnology is crucial.”

To read more about Lisa and her career path, click here.

A Review of the Patent Related Provisions of the TPP – Patent Revocation, Publication and Delays

This is our second post examining certain of the patent related provisions of the Trans-Pacific Partnership (TPP) from the WikiLeaks released final “agreed version of the TPP chapter on intellectual property rights.  Our first post, which examined patentable subject matter and grace periods, can be found here. In this post, we review the TPP provisions relating to patent revocation, publication of patent applications and procedures for adjusting patent term due to an unreasonable delay by a patent office.

Procedures allowing for patent revocation

Section QQ.E.3 provides that each country shall provide procedures to allow a patent to be cancelled, revoked or nullified, but only on those grounds that would have justified a refusal to grant a patent. A country may also provide that fraud, misrepresentation or inequitable conduct may provide a basis for cancelling, revoking or nullifying a patent or holding a patent unenforceable. A country may provide that a patent can be revoked in a manner consistent with Article 5A of the Paris Convention and the TRIPS Agreement.

Publication of Patent Applications

Section QQ.E.11 provides that each country shall “endeavor” to publish (unpublished) patent applications promptly after expiration of 18 months from the filing date, or, if priority is claimed, from the priority date. If an application is not published, then the application or corresponding patent must be published as soon as practicable. Moreover, each country is required to provide procedures for the early publication of an application (prior to the expiration of 18 months from the filing date or earliest claimed priority date).

Patent Office Delays

Section QQ.E.12 provides that each country shall use its “best” efforts to process patent applications in an “efficient and timely manner” and avoid “unreasonable or unnecessary delays”. Additionally, each country may provide procedures that allow an applicant to request expedited examination of a patent application. Moreover, this section provides that in the event of unreasonable delays in a country’s issuance of an applicant’s patent, mechanisms shall be provided that shall “adjust the term of the patent to compensate for such delays” upon the request of the patent owner.

An “unreasonable” delay includes at least a delay in the issuance of a patent of more than five years from the date of the filing of the application in the territory, or three years after a request for examination of the application has been made, whichever is later.

A country may exclude from the determination of such delay, periods of time that:

  1. Do not occur during the processing (meaning the initial administrative processing as well at the time of grant) of or the examination of, the patent application by the granting authority;
  2. Are not directly attributable (namely, those that are outside the direction or control of the granting authority) to the granting authority; and
  3. Are attributable to the applicant.

This post was written by Lisa Mueller.