I recently wrote about my experiences teaching a course, Intellectual Property and Healthcare Technologies, at Cornell Law School. I received a lot of questions and comments about that post so I decided to write a follow up with a few more lessons that I learned while teaching at Cornell Law. I hope these lessons can teach both instructors and students (after all, aren’t we all students?) about what worked for me and how some of these lessons can be incorporated into presentations, written materials, and even daily practices.
First, the benefit of collaborations cannot be understated. As I previously mentioned, since my course at Cornell was longer than my course at Harvard, I had the opportunity to expand the subject matter that I taught. To help teach some of the new topics, I engaged experts from the field to help lead the class discussions. In particular, I invited Michael Carrier, a leading expert in pharmaceutical antitrust law and Distinguished Professor at Rutgers Law School, and Joe Fuhrer Jr., Professor Emeritus of Economics Widener University, to teach classes on antitrust and drug pricing, respectively. Not only did I get to know these two professionals better by inviting and hearing them lecturer, but so did the students. Networking is an important part of almost any job, especially in business and law, and the students and I both benefited from having these experts present.
Second, working with students throughout the semester resulted in better final papers. I know many people like to procrastinate when writing their papers, whether it be a final paper for a class, a brief, an agreement, or even a patent application. I know I certainly did. The lesson I learned, however, is that the students who started outlining and writing their papers and submitted their papers to me for comments early on in the semester were the ones who ended up producing the better papers. Rarely is anything you write perfect the first time around. To produce your best possible product, you have to start early, receive feedback (whether from a teacher, a colleague, or a client), and implement the necessary changes to take your paper to the next level.
Third, examples, example, examples! The life science industry is certainly filled with examples on any given topic, particularly when it comes to drugs and the controversies surrounding them. One of the biggest improvements I made to my slides this year was adding more real-life examples. If we talked about building a diverse patent portfolio, we looked at Humira® and the 100+ patents protecting that drug. If we talked about antitrust, we examined the current case surrounding Remicade®and allegations of inappropriate rebates and bundling. If we talked about potential legislative reforms to the brand and generic/biosimilar dynamic, we evaluated recent proposals by Congress, the FDA, and the Trump administration. I also encouraged students to include specific case studies and examples in their papers to better illustrate the points they were trying to make. Providing examples not only puts concepts into perspective, it also makes presentations and papers more engaging.
Fourth, I encouraged students to publish their works. As mentioned in my first point, networking is a very important part of one’s job in business and law. Another part of the job is getting your name out there and being recognized. One great way of doing that is to write and publish your work. When I first started practicing, I was fortunate enough to work with partners who really valued the benefit of publishing legal articles whether it be in newspapers, magazines, or business journals. As a result, I got into a habit of writing and publishing my work. Many of my speaking opportunities down the road and clients that I engaged came because someone read something that I wrote. Since my class was a writing class and students had to write a paper, I also wanted to encourage them to try to get their papers published. By publishing their papers, not only are the students be able to add a publication to their resumes, but they also start getting their names out there.
Finally, take any opportunity you can find for personal and professional growth. Since I had to drive every week to and from Cornell (about an hour and forty-five minutes each way), I spent a lot of time in the car by myself. I took this time to listen to audiobooks through Audible. In fact, the best thing I did for myself last year was to invest in Audible. I listened to everything from negotiation books such as Never Split the Difference, to personal development books such as The Power of Habit, to fun books like Crazy Rich Asians. I admittedly did not achieve many of the professional goals I had set for myself for 2018, but I did achieve my goal of reading (or listening to) at least 60 books in 2018! I have a whole list of books that I can highly recommend if anyone is interested. Time alone in a car is not only a good time for reflection, but also a good time to consume information. Listening to audiobooks was a great way for me to learn a lot of new content while also making my drive more enjoyable.
I hope you enjoyed learning from my experiences. Please feel free to reach out with any questions or comments.
Last week Bristol Myers Squibb (BMS) announced that it planned to acquire Celgene in a deal valued at $74 billion. Following the acquisition, the resulting company will have nine products in its portfolio that each generate more than $1 billion a year. This portfolio will include Celgene’s Revlimid®, a derivative of thalidomide (lenalidomide) used to multiple myeloma (MM), transfusion-dependent anemia due to myelodysplastic syndromes (MDS), and mantel cell lymphoma. Revlimid® sales exceeded $8 billion in 2017, but there are questions surrounding its long-term value since it may face generic competition in 2022 by Dr. Reddy’s.
A settlement conference is scheduled for tomorrow, January 10, 2019, in the Hatch-Waxman patent case between Celgene and Dr. Reddy’s. To date, the parties have not been able to reach a settlement. However, this may now change with Bristol Myers at the table.
Celgene has many patents protecting Revlimid®, including a composition of matter patent covering lenalidomide (U.S. Patent No. 5,635,517) which expires in October 2019. The other patents mainly fall into two categories: method-of-use or indication patents and polymorph patents. The method-of-use patents mostly expire by 2022 but the polymorph patents, including U.S. Patent Nos. 7,855,217 and 7,465,800, do not expire until 2024 and 2027, respectively. Revlimid’s® long-term value thus stems from these polymorph patents which look to extend Revlimid’s® monopoly past 2022.
In terms of generic competition, Celgene faced an early threat from Natco back in 2010, which ended in a settlement in 2014 that would allow Natco to enter the market with a limited quantity of product in 2022 and gradually increasing to an unlimited quality in 2026. At least according to this settlement, the generic cliff for Revlimid® would not fully be 2022, but rather 2026. This agreement most likely includes, although we have not been able to verify through public documents, an acceleration or most-favored-nation provision that would allow Natco to enter the market sooner if a subsequent generic was able to obtain a better entry date.
Since Natco, several other companies have filed ANDA’s against Revlimid®, including Dr. Reddy’s, Zydus, Cipla, and Lotus Pharmaceuticals. The case with Dr. Reddy’s is the furthest along. Although a trial date has not yet been scheduled, it would likely take place in the second or third quarter of 2019, as the parties have thus far been engaging in discovery.
The trial will likely focus on the polymorph patents and Dr. Reddy’s argument that is does not infringe those patents because its generic product is “amorphous” lenalidomide, whereas the patents are limited to “crystalline” lenalidomide. Dr. Reddy’s thus believes it can circumvent the polymorph patents. Celgene, on the other hand, will likely argue that even though Dr. Reddy’s product is amorphous at certain stages, it is also crystalline at others. There is at least some support for this type of argument as the Federal Circuit suggested in a 1994 case (Zenith Laboratories, Inc. v. Bristol-Myers Squibb Co.) that a drug that is not infringing when made or sold, but converted into a patented polymorph when ingested, may be infringing.
Another possible venue for challenging the polymorph patents would be through an inter partes review (IPR) proceeding. Dr. Reddy’s, however, chose not to challenge the polymorph patents that way, focusing instead on challenging three MDS patents which expire in 2022. There are two potential reasons why Dr. Reddy’s chose not to challenge the polymorph patents through an IPR. First, IPR challenges are limited to Section 102 and Section 103 issues, meaning that you are challenging the validity of those patents. Dr. Reddy’s appears to be arguing that its product does not infringe, which is not an appropriate argument for an IPR. Second, if Dr. Reddy’s were to challenge the polymorph patents in an IPR and win, then it would open the door for other generics to launch their products. By arguing non-infringement in a district court litigation rather than invalidity in an IPR, Dr. Reddy’s can keep other generics off the market.
To date, Celegene and Dr. Reddy’s have not been able to resolve their differences and it appears as though they are headed for trial. One main obstacle to settlement has been Celgene’s prior settlement agreement with Natco, which limits what Celgene can offer Dr. Reddy’s.
Nevertheless, Dr. Reddy’s probably wants to beat Natco to the market. If Dr. Reddy’s can successfully show non-infringement of the polymorph patents, and wait for the expiration of the other patents, then it could enter the market with an unlimited quantity by 2022. This would be a better outcome than the one that Natco received.
BMS’s presence at the table may change the dynamics of any potential settlement. While Celgene may not have had the ability or the economics to broker a settlement, the new BMS/Celgene entity with its new product pipeline and business model just may.
We will keep you informed of any new developments following the January 10 settlement conference.
With the JP Morgan Healthcare Conference taking place this week in San Francisco, we thought it would be worth looking at the issues that biotech companies need to remember about intellectual property (IP) when pitching to investors. At BioPharma Law Group, we help our clients prepare and finetune their presentations to investors, and we also act as judges in startups competitions. Based on these experiences, we provide below a list of IP issues that start-ups should keep at the top of their mind when making an investor pitch.
First, know your own IP. Make sure you are familiar with your patent portfolio and know exactly which patent applications you have filed, where they stand in prosecution, and who owns them. If you are licensing IP from somewhere else, whether it be a university or other company, be prepared to discuss whether your license is exclusive or not. If the technology involves core IP, and your license is not exclusive, you may have to explain why you think you do not need an exclusive license. Moreover, know the scope of your patents. Be prepared to talk about at least your main claims and how they cover the product that you are trying to develop and eventually market. If your claims do not cover the product, be prepared to discuss why and what you can do to improve them. This may include strategies for filing continuation applications or follow on applications to yield the desired claim scope.
Second, know proper IP terminology. Do not say that you have a “patent” when in fact you only have a patent application on file. Patent terminology can be difficult for the lay person. Practitioners such as us do not always appreciate this fact since we deal with patents and patent applications on a daily basis, but we cannot emphasize enough the importance of accurately and properly discussing your IP. Investors know IP terminology and using improper terminology will not only confuse the investors, but it could also reduce the value of your technology in their eyes or give the impression that the start-up is not really ready for investment. Saying that you have an “international patent in many countries” can mean a variety of things, or it can mean nothing at all. Work with your company’s IP counsel to make sure you understand what you actually have in your IP portfolio and what you need to focus on in your presentation.
Third, know your competitor IP. Unless you discovered some groundbreaking technology, chances are you have competitors. Every company looking for investors has IP competition. Be prepared to discuss your competitors, their IP (i.e. the patent landscape for your market), and what your company’s strategy is for steering around any IP landmines. This may include plans for licensing certain competitor IP or designing around it.
Fourth, know your company IP strategy. Have an IP strategic plan. Investors do not expect you to have dozens of patent applications already filed but they do expect you to be able to tell them how you plan on building on what you already have and avoiding known patent threats in your target market. Further, any strategic plan should include cost estimates and ballparks for patent applications you plan to file in the future and where you plan to file them and why. Other key components include fleshing out whether your company will be filing on a platform technology, improvements on established technology, or new embodiments of technology. Your company may also need to license or acquire certain IP already existing in your field to bring your product to market. Be prepared to discuss how and when you plan on accomplishing that goal.
Finally, know the current patent and regulatory environment and how it may impact your strategic IP plan. Depending on your specific technology, the current patent climate may have significant implications on your ability to get the claims you want. Top of the list of issues today include 35 U.S.C. Section 101 subject matter issues and 35 U.S.C. Section 112 written description issues. If you are developing biologics, the current climate favoring biosimilars and generic drugs may be problematic for you. If your technology falls within the types that may be affected by today’s uncertain patent and regulatory climates, be prepared to discuss how you plan on mitigating that risk and what backup positions you might pursue.
Good luck to everyone participating in JP Morgan this week!
I recently concluded my first semester of teaching my course Intellectual Property and Healthcare Technologies at Cornell Law School. This was not my first time teaching the course. In fact, I have taught it six previous semesters at the Harvard School of Public Health. However, in the seven semesters that I have taught the class, I am always amazed by what I learn, both from the course material and from the students. Below are five lessons that I learned from teaching my course this semester.
Overall, I really enjoyed teaching my class at Cornell. I hope to take some of the lessons learned from this semester to make the class even more informative and valuable next year.
On December 4, 2018, the District Court for the Eastern District of Pennsylvania again denied Johnson & Johnson and Janssen’s (“J&J”) motion to dismiss antitrust claims regarding sales of its blockbuster biologics, Remicade. In this case, retailers Walgreens and Kroger are suing on behalf of themselves and as the assignees of AmerisourceBergen Drug Corporation and Cardinal Health, Inc., respectively, who are pharmaceutical wholesalers that directly purchased Remicade from J&J for resale to Walgreens and Kroger. Walgreens and Kroger allege antitrust injury because they pay higher prices for Remicade as a result of J&J’s “Biosimilar Readiness Plan,” which involves exclusive agreements and rebate bundling with insurers and health care providers and prevents lower-priced biosimilar versions of Remicade to compete.
J&J moved to dismiss the claims on two grounds. First, J&J argued that the retailers lacked antitrust standing because they do not have consent from the distributors to pursue these claims, as may be required under their distributor agreements. To consider whether the retailers have antitrust standing and whether the distributor agreement encompasses their antitrust claims, the Court decided that it will have to interpret the agreements. To this end, the Court converted J&J’s motion to one for summary judgment and agreed to hear additional evidence.
Second, J&J argued that the retailers failed to sufficiently allege antitrust injury. J&J’s primary argument was that the retailers failed “to plead specific facts showing that Pfizer and Merck were excluded from competing in the infliximab market by Defendants’ Biosimilar Readiness Plan, rather than choosing not to compete.” In this regard, the Court denied the motion, finding that J&J’s Biosimilar Readiness Plan foreclosed lower priced biosimilar infliximab drugs from competing with Remicade and resulted in retailers paying “inflated prices for those products.”
This is the second time that the Pennsylvania Court has denied J&J’s motion to dismiss a lawsuit dealing with Remicade. We previously wrote that on August 10, 2018, the Court denied J&J’s motion to dismiss Pfizer’s antitrust lawsuit relating to its biosimilar, Inflectra. In that case, Pfizer sued J&J alleging that J&J has been conducting “anti-competitive practices,” such as forcing hospitals and insurers to enter exclusive arrangements and bundled rebate programs, to prevent biosimilar competition by preventing health insurers, hospitals, and clinics from offering Pfizer's lower-priced biosimilar product.
The results of these antitrust cases will be important for companies developing innovator and biosimilar products alike as these cases will likely provide more insights on which pricing practices are permissible under antitrust laws and which are not. We will continue to monitor the case and provide updates as they become available.
Contractors should take note of the recent changes to the landmark 1980 Bayh-Dole Act. Almost 40 years later this piece of legislation has proven its worth as critically important to the vibrant US start-up scene, especially in the biotech/biopharma field.
Bayh-Dole made it possible for US universities, not-for-profit organizations and companies to retain the ownership of inventions "conceived or first actually reduced to practice” in their laboratories with government funds, for example grants doled out by the National Institutes of Health, the National Science Foundation or the Department of Health and Human Services. Before Bayh-Dole the government owned all inventions made with grant money which often were not commercially utilized.
But Bayh-Dole did not stop there, it also encourages universities to promote the utilization of their patents and other IP by actively looking for the best way of commercializing the inventions, e.g. by licensing them. Bayh-Dole encourages utilization of intellectual property created with tax payer money and with that, ultimately, benefits the public.
Under Bayh-Dole the inventor has to fulfill a number of conditions to be able to retain ownership of an invention. Some of the most important ones are:
If the contractor fails to comply with these regulations the grant giving agencies of the government can elect – but do not have to - to request title to the invention within 60 days of the contractor’s non-compliance.
The May 2018 Amendments to Bayh-Dole and What They Mean
In 2016 the Secretary of Commerce gave the National Institutes of Standards and Technology the authority to suggest changes to the Bayh-Dole regulations. These changes went into effect on May 14, 2018. Following is an overview of the most critical changes:
Formalizing the Expansion to Include Large Companies
The right to retain the title to an invention was expanded to include large companies - in addition to small companies and nonprofit organizations – via an Executive Order in 1987. Only now, however, were the implementing regulations in 37 C.F.R formally amended to include this expansion. The revised 37 C.F.R. § 401.1(b) now explicitly states that it applies “to all funding agreements with firms regardless of size.”
This clarification finally makes sure that all contractors, regardless of their size, are subject to the same set of rules with respect to the treatment of inventions.
Removal of the 60-Day Election Limit
The 60-day limitation for the government to elect to request title to the invention after a contractor’s non-compliance has been eliminated.
This change is very important as it seems to give the government unlimited time to take title from a non-compliant contractor instead of just 60 days. This leaves the contractor with just one option for recourse, namely seeking a retroactive extension of time. Granting this extension is at the discretion of the agency and therefore probably a long shot in a case where the agency has decided to take title of the invention. Contractors need to make sure to adhere to the timelines to avoid inadvertent transfer of title.
Responding to USPTO Office Action
Previously contractors had to notify the agencies of a decision not to prosecute an application within 30 days before a response was due to an Office Action issued by the USPTO. This period has now been extended to 60 days.
This amendment seems small but spells potential trouble for contractors who tend to respond to Office Actions late in the allotted response period (typically: an initial three-month response deadline and three additional months of extensions). The new 60-day rule requires a decision whether to respond to the Office Action within the first 4 months after receipt.
The Case of the Federal Agency Employed Co-Inventor
In addition, the amendments address a number of issues that previously left room for interpretation. One such area is a joint invention where a co-inventor is a federal employee. The amendments clarify that the federal agency, at its discretion but in consultation with the contractor, can file the initial patent application, provided the contractor retains its ability to elect rights. This means that the agency that employs a government employee co-inventor now has patenting priority over the funding agency when the contractor has declined to elect title.
For contractors this means that they have to carefully evaluate joint invention scenarios; it is likely to in their best interest to control the patent prosecution rather than leave it to the federal agency that employs the co-inventor.
Requirement of Written Assignments
Another amendment expands the duty of contractors vis-a-vis their employees. Previously, a contractor had to get written agreements from each employee stating that they would promptly disclose any invention to their employer (the contractor). The amendments add an additional requirement: contractors also have to obtain written assignments from all their employees stating that they assign all rights and title to any inventions to them.
This addition is considered a reaction to the Supreme Court ruling in Stanford vs. Roche and an attempt to temper that ruling.
Provisional Patent Application
The previous version of Bayh-Dole required a contractor to file PCT and/or foreign patent applications within 10 months of filing an initial US application. The amendment expands these filing requirements to non-provisional applications filed after an initial provisional application. If these timelines are not met, the Federal Agency has the right to obtain the title to the invention.
For contractors, paying close attention to filing dates and deadlines is now even more important than it used to be.
Government grants are very attractive for founders or companies looking to grow their business or undertake potentially risky but rewarding R&D. And although government money comes with strings attached those strings are generally considered well worth it for the title to the inventions. For contractors it is therefore very important to make sure they are aware of the changes to Bayh-Dole and adhere by the new timelines and requirements to not jeopardize their ability to obtain and retain title. To this end, companies should review any funding agreements governed by the Bayh-Dole Act to ensure compliance with the regulations to avoid any unnecessary surprises down the road with respect to patent ownership.
On Monday, October 22, 208, the US Court of Appeals for the Federal Circuit issued another blow to Allergan’s deal with the Saint Regis Mohawk Tribe (“Tribe”) by refusing to reconsider an earlier decision that rejected use of tribal sovereign immunity in inter partes reviews (IPRs). This is the latest setback for Allergan and the Tribe in their efforts to avoid IPRs before the Patent Trial and Appeals Board (“PTAB”).
As a general background, in September 2017, Allergan announced that they entered into an agreement with the Saint Regis Mohawk Tribe (the Tribe) in which Allergan transferred ownership of all Orange Book-listed patents for RESTASIS® (Cyclosporine Ophthalmic Emulsion) 0.05% to the Tribe, while being granted exclusive licenses in the patents related to the product. The patents transferred to the Tribe included U.S. Patent Nos. 8,629,111; 8,633,162; 8,642,556; 8,648,048; 8,685,930 and 9,248,191. RESTASIS® is an important product for Allergan since it generated around $1.5 billion in 2017. By transferring ownership of the RESTASIS® patent portfolio to the Tribe, Allergan and the Tribe hoped to dismiss the ongoing IPRs of the RESTASIS® patents based on the Tribe’s status of being a recognized sovereign tribal government to which sovereign immunity applies.
Thus far, however, Allergan’s strategy to avoid IPR challenges has faced significant hurdles. In February 2018, the PTAB rejected the attempt to dismiss based on tribal sovereign immunity, finding that Allergan retained ownership in the patents and the Tribe retained nothing more an “illusory or superficial right” to sue for infringement of the challenged patents. According to the PTAB, “[i]n view of the recognised differences between the state sovereign immunity and tribal immunity doctrines, and the lack of statutory authority or controlling precedent for the specific issue before us, we decline the tribe’s invitation to hold for the first time that the doctrine of tribal immunity should be applied in IPR proceedings.”
In July 2018, the Federal Circuit upheld the PTAB’s decision, concluding that tribal sovereign immunity cannot be asserted in IPRs, and therefore cannot be used to dismiss the IPRs filed against Allergan.
A month later, in August 2018, Allergan and the Tribe requested a panel rehearing and an en banc rehearing. This request was denied on Monday.
Despite the recent denial, Allergan and the Tribe can still appeal to the U.S. Supreme Court.
Allergan’s controversial move to circumvent IPRs in an effort to stave off generic drug entry adds fuel to the ongoing debate over IPR proceedings. We will keep you informed of developments related to IPRs as they occur.
On October 10, 2018 President Trump signed into law the “Patient Right to Know Drug Prices Act” (S.2554) which requires antitrust scrutiny of biosimilar settlements by the Federal Trade Commission (FTC). The law amends the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 to require Reference Product Sponsors and biosimilar applications to submit their settlement agreements to the FTC for review. The bill was introduced in March 2018 by Senators Susan Collins (R-Maine), Clair McCaskill (D-Missouri), and Debbie Stabenow (D-Michigan).
The new law will allow the FTC to access the terms of a deal without seeking additional authority from the commission. It will also allow the FTC to track biosimilar deals and develop a data record of relevant terms, similar to what has been down with small molecule generics.
The law comes at an important time. Humira®, which is the best-selling drug in the world yielding more than $18 billion in sales in 2017, entered the market in Europe this past Tuesday on October 16, 2018. However, no biosimilars of Humira® are expected to enter the market in the US until at least 2023. This is because in the US, AbbVie not only maintains a robust patent portfolio protecting Humira®, it has also reached deals with multiple biosimilar manufacturers, including Amgen, Samsung Bioepis, Mylan, Sandoz, and as of yesterday, Fresenius Kabi, to hold off competition until 2023.
Apart from this new law, other legislations addressing settlement agreements are also moving forward in Congress. It will be interesting to see if these legislations will increase the entry of biosimilars on the US market.
We will keep you informed of any new developments in this field.
It has been one year since the Federal Circuit issued its opinion in Amgen v. Sanofi that raised the hurdle for protecting antibody inventions by requiring more data when disclosing and claiming antibodies. Since the court decision on October 5, 2017, it has become more challenging for pharmaceutical companies to obtain broad protections for therapeutic monoclonal antibodies. While obtaining protection for antibodies is still very much possible in this current climate, certain types of claims are now more susceptible to attack and possible invalidation. Below we analyze the different types of claims protecting antibody inventions and discuss their relative strengths in the wake of Sanofi.
In Amgen v. Sanofi, the Federal Circuit ruled that in order to obtain broad patent coverage for a class of antibodies that bind to a particular antigen and perform a particular function, companies must disclose a sufficient number of representative antibodies across the claimed genus or establish a clear relationship between the function of the antibody and the genus of the antibody in their specification. In Sanofi, the claims were directed to a monoclonal antibody that bound to one or more of 15 different amino acid residues on the sequence of the target antigen and performed a certain function (e.g., blocked the antigen from binding to its target). Claim 1 of U.S. Patent No. 8,829,165 ("'165 patent") is representative. It recites:
“An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDL[-]R.”
To support its claim that antibodies that bound one of the 15 residues or any combination of them were covered by the patent, Amgen disclosed two specific antibodies with binding data and affinity data. These data probably would have been sufficient prior to Sanofi. In Sanofi, however, the Federal Circuit ruled that such disclosure was insufficient. The court noted that patent specifications must disclose a representative number of species of the genus of claimed antibodies in order satisfy the written description requirement. The Federal Circuit did not, however, provide any guidance as to what a “representative number” of species would be. Therefore, it still remains an open question as to what counts as a representative number of species remains today.
Below we review several types of antibody-related claims in search of trends on which types of claims have fared better than others in the last year.
Historically, one of the broadest types of claims a company could get to an antibody was by its function. Functional claims to a genus of antibodies typically recite the functional property of an antibody without reciting any sequence information, for example “an antibody that binds to target Y”. Similarly, functional claims can be in the form of competition claims where “an antibody that competes with antibody X for binding to antigen Y” is covered. While such broad claims can cover nearly any antibody in a group of antibody products that are directed to the same target, such functional claims are becoming increasingly vulnerable in light of Sanofi, as courts will require a “representative number” of examples of the genus, i.e. a representative number of antibody sequences and associated binding data.
Method of Use/Treatment
Method of use or method of treatment claims have also proven to be vulnerable as these types of claims have not fared well when challenged in an Inter Partes Review (IPR) at the PTAB. These types of claims are by far the most popular target of IPR petitioners. In a study of antibody-related IPR petitions, the IPR petition grant rate on method of treatment claims is 65% (24 petitions granted, 13 denied), but, in all 6 of the Final Written Decisions to date, all instituted claims were held unpatentable. Therefore, it appears that if the PTAB institutes an IPR on a method of treatment antibody claim, those claims are likely to be found unpatentable. One potential reason for why these types of claims are easy to invalidate is because if you knew the antigen and what it does, it would be obvious to develop an antibody to treat people against that antigen. As such, method of use and method of treatment claims are probably the weakest types of claims in protecting antibodies.
On the opposite side are sequence claims. These types of claims define an antibody by its structure, which is most commonly claimed by its six complementary determining regions (CDRs), by its two variable regions, or even by its heavy and light chain sequences (both cDNA and peptide sequences). Patent prosecutors keen on obtaining the most protection for clients will attempt to claim sequences by the shortest and fewest number of sequences possible. Often times the amount of sequence data needed to pass examination hurdles will depend on the examiner. These types of claims will likely survive invalidation attempts because they are specific to one particular antibody. However, while antibody sequence claims are a strong type of claim to have, they are also the narrowest option, which makes them easier for a competitor to design around.
Besides claiming the antibody itself, a company can claim a pharmaceutical composition or formulation. While these types of claims are theoretically easier to design around because they include the antibody structure, they appear to be successful in surviving IPR challenges at the PTAB. In fact, the PTAB rarely institutes challenges to composition claims, and when it has, the claims almost always survive. Antibody formulation claims are the second most frequently challenged type of antibody claim behind method of treatment claims, discussed above. However, of the 13 IPRs that have been filed against claims to antibody formulations, three were instituted and 10 were denied. In the three instituted IPRs, all of the claims survived the challenge. Of the IPR petitions that were denied, most were because the petitioner failed to establish “a reasonable likelihood that the petitioner would prevail.” It is likely that these types of claims survive challenges because there is high unpredictability in the art since even small changes in antibody formulations can have unexpected effects on protein aggregation, viscosity, and other factors, making it harder to prove that such formulations are predictable and obvious. As such, pharmaceutical formulation patent are important to include when deciding how to protect antibodies.
A final type of patent for protecting an antibody is to develop antibody conjugates. These types of claims describe an antibody with a particular sequence fused to, or conjugated to, a drug. In an IPR challenge to Kadcyla®, an antibody-drug conjugate consisting of the monoclonal antibody trastuzumab, Herceptin®, linked to the cytotoxic agent emtansine, the PTAB ultimately upheld the claims because a person skilled in the art at the time of the invention would have expected Herceptin®-maytansinoid immunoconjugates to be unacceptably toxic. While claims to antibody conjugates may survive obviousness challenges, it is important to remember that they are also narrower because they describe both the antibody sequence and a drug. They will also likely face challenges as to how much data and support is required to be in the specification to broadly claim the antibody conjugate. Nevertheless, these types of claims may be valuable to an antibody patent portfolio.
The case law in the antibody space has made it more challenging for companies to obtain broad protections for therapeutic monoclonal antibodies, especially in the wake of the Sanofi decision. To maximize the value of your antibody portfolio, it is therefore important to review the antibodies on a case-by-case basis and decide which features to claim based on the amount of data and investment available.
Brand companies employ a variety of mechanisms to maintain their market exclusivity and delay generic entry. We have recently written about Johnson & Johnson’s rebate and bundling schemes in trying to hinder uptake of a Remicade® biosimilar. We have also written about Allergan’s attempts to sell its patents covering Restasis® to an Indian tribe in an effort to avoid inter partes review challenges. Well, Allergan again finds itself again in the middle of a dispute that touches on intellectual property, this time Allergan is alleged to have engaged in anticompetitive practices to delay generic competition because of its misuse of citizen petitions.
While citizen petitions are supposed to allow citizens an opportunity to raise legitimate safety concerns with the U.S. Food and Drug Administration (FDA), they have often been misused by innovator drug companies as a way of delaying generic market approval. One study analyzed all citizen petitions filed with the FDA between 2011 and 2015 that targeted pending generic drugs and found that innovator manufacturers file 92% of all the citizen petitions, with the FDA denying nearly all these petitions.
This situation arose recently in a class action case filed against Allergan Inc. alleging antitrust violations aimed at protecting its dry-eye drug Restasis®. Amongst other violations, the suit alleged that Allergan filed four baseless citizen petitions in an effort to hinder generic competition. Allergan filed a motion to dismiss this claim asserting that the suit was “meritless”.
Last week, however, U.S. District Judge Nina Gershon shot down Allergan’s efforts to sidestep the suit and sided with plaintiff union benefit plans and various pharmaceutical purchasers, claiming that it is probable that Allergan acted dishonestly in hindering generic competition.
In its ruling, the Federal judge declined to apply the Noerr-Pennington doctrine, which shields good-faith petitioning of the government even if it results in a competitive edge. She provided two reasons for not applying the doctrine.
First, Judge Gershon noted that the doctrine does not protect “objectively baseless” petitioning. Since the FDA denied each of Allergan’s petitions, the Judge found that it could be probably that the petitions were scientifically unfounded.
Second, Judge Gershon noted that that the doctrine does not protect actions that are solely intended to hinder competition. Since Allergan petitioned the FDA repeatedly asking for testing of generic Restasis® in human, something not required for generic drugs, and then did not appeal the FDA’s rejections of its petitions but instead filed subsequent petitions using duplicative motives, the Judge found that Allergan’s actions could show that Allergan filed the petitions with improper motives. According to Judge Gershon, “[i]t is highly plausible that a company willing to engage in such conduct was intending to delay the entry of generics into the market, rather than seeking to protect the public health.”
Citizen petitions are a legally protected act so attacking them under antitrust law has traditionally been difficult. To prove that a citizen petition violates the law, plaintiffs have to show they are so baseless that they constitute a total sham. This case shows that its is possible to clear the first hurdle in demonstrating that citizen petitions are a sham and thus shows a possible path forward for generic drug plaintiffs hit with such petitions in future disputes.
BioPharma Law Blog posts updates and analyses on IP topics, FDA regulatory issues, emerging legal developments, and other news in the constantly evolving world of biotech, pharma, and medical devices.