Amgen is at it Again – Sues Hospira For Not Wanting to Dance Over its Biosimilar

On September 18, 2015, Amgen Inc. (Amgen) sued Hospira Inc. (Hospira) in the U.S. District Court for the District of Delaware for allegedly violating the information sharing and advance-notice provisions of the Biologics Price Competition and Innovation Act of 2009 (BPCIA) as well as for infringement of U.S. Patent Nos. 5,856,298 and 5,756,349.

In December 2014, Hospira submitted a 351(k) application (Biologic License Application No. 125545) to the U.S. Food and Drug administration (FDA) for a biosimilar version of Amgen’s anti-anemia drug EPOGEN® (epoetin alfa). EPOGEN® was approved by the FDA for the treatment of anemia associated with chronic renal failure (including end-stage renal disease). Over time, additional approvals were obtained, specifically, for use in patients with certain cancers suffering from anemia due to concomitant chemotherapy and in patients with HIV infection and anemia due to antiviral drugs. Since approval, Amgen has manufactured and sold EPOGEN® in the U.S. for the treatment of anemia associated with chronic kidney disease in patients with dialysis. FDA is expected to complete its review of Hospira’s product by November 2015.

On February 23, 2015, Hospira notified Amgen that its 351(k) application had been accepted by the FDA. On March 3, 2015, Hospira provided a copy of its application to Amgen but did not provide its marketing information as required by the information-sharing provisions of the BPCIA. Amgen sent four letters to Hospira (on March 31, April 17, April 27 and May 1, 2015) identifying that the manufacturing information was missing. Hospira allegedly refused to provide this information (and thus, did not provide the information within 20 days of receiving notification of FDA acceptance of its application for review).

Despite the absence of the manufacturing information, Amgen engaged Hospira in the patent exchange process of the patent dance. Specifically, Amgen provided Hospira with a list of patents Amgen believed could be reasonably asserted within 60 days of receipt of Hospira’s 351(k) application. Additionally, within 60 days of receiving Hospira’s statement, Amgen provide its reciprocal statement on a claim-by-claim basis as well as the factual and legal basis for its opinion that each patent was infringed as well as a response to Hospira’s statement regarding validity and enforceability. However, Amgen alleges that Hospira has refused to engage in “good-faith negotiations” to agree which, if any, patents would be the subject of an action for patent infringement. Instead, Hospira decided simply to “accept” the patent listed by Amgen.

Regarding the advance-notice provisions, on April 9, 2015, Hospira provided Amgen with 180-day advance notice of commercial marketing. On May 8, 2015, Amgen objected stating that the notice was premature (and hence invalid) but Hospira allegedly refused to withdraw it. On August 18, 2015, after the Federal Circuit issued its decision in Amgen v. Sandoz (Amgen), Amgen renewed its objection and requested Hospira confirm that it would follow the law. However, according to the complaint, Hospira allegedly refused to acknowledge the import of the holding in Amgen and according to correspondence dated August 19 and September 15, 2015, took the position that it would not provide any notice of commercial marketing. Specifically, in its complaint Amgen states that “Hospira has categorically represented to Amgen that it does not intend to provide Amgen with notice of commercial marketing after the FDA licenses the Hospira Epoetin Biosimilar Product and 180 days before commercial marketing of the Hospira Epoetin Biosimilar Product is to be begin”.

In addition to patent-specific relief, some of the relief Amgen requested includes:

  1. An order enjoining Hospira from commercially marketing its biosimilar version of EPOGEN® until Amgen is restored to the position it would have been had Hospira met its obligations under the BPCIA;
  2. An order enjoining Hospira from continuing to seek FDA review of its 351(k) application and/or compelling Hospira to suspend FDA review of its application until Hospira obtained permission from Amgen to use the EPOGEN® license or Hospira has restored Amgen the benefits afforded to reference product sponsors under the BPCIA;
  3. A declaration that the notice of commercial marketing that Hospira provided on April 9, 2015 was ineffective;
  4. An injunction requiring Hospira to provide Amgen, on or after FDA licensure of its biosimilar, notice of the date of first commercial marketing and prohibiting Hospira from beginning such marketing until 180 days after Hospira provides the requisite notice; and
  5. A declaration that Hospira violated the BPCIA by failing to provide Amgen with its manufacturing information by the statutory deadline.

Please continue to watch the BRIC Wall Blog for updates on this and other biosimilar litigation.

This post was written by Lisa Mueller

Indian Patent Office Rejects Pfizer’s Patent for Tofacitinib – Again!

Background

Pfizer Products, Inc. (Pfizer) filed Indian patent application 991/MUMNP/2003 (‘991 application) entitled “Chiral Salt Resolution” in the Indian Patent Office (IPO) on October 27, 2003. The ‘991 application is a national phase application of WO 02/096909 (PCT/IB02/01905) filed on May 29, 2002. WO 02/096909 claims priority to U.S. application no. 60/294,775 filed on May 31, 2001 and U.S. application no. 60/341,048 filed on December 6, 2001.

The ‘991 application describes methods for effecting chiral salt resolution from racemic mixtures of enantiomers, particularly precursor enantiomers, for use in making pyrrolo[2,3-d]pyrimidine compounds. The pyrrolo[2,3-d]pyrimidine compounds are inhibitors of protein kinases, such as the enzyme Janus Kinase 3 (JAK3). The specification describes the enantiomer, 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile, also known as tofacitinib.   Tofacitinib, which is sold as XELJANZ®, is approved for use in the treatment of rheumatoid arthritis.

The closest prior art, WO 01/42246 (D1), also owned by Pfizer, was filed on November 23, 2000 and published on June 14, 2001. D1 claims priority to U.S. application no. 60/170,179 filed on December 10, 1999. D1 relates to pyrrolo[2,3-d]pyrimidine compounds (which are inhibitors of protein kinases, such as JAK3) and the use of these compounds in the treatment of various diseases, such as lupus, multiple sclerosis, rheumatoid arthritis, etc. Example 14 of D1 discloses 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile, the racemate of the enantiomer claimed in claim 1 of the ‘991 application. Additionally, D1 discloses all conformational isomers (e g., cis and trans isomers). Although D1 does not disclose any specific enantiomers, it teaches that compounds have asymmetric centers and thus exist in different enantiomeric and diastereomeric forms. Specifically, the specification states, “This invention relates to the use of all optical isomers and stereoisomers of the compounds of the present invention, and mixtures thereof, and to all pharmaceutical compositions and methods of treatment that may employ or contain them. In this regard, the invention includes both the E and Z configurations. The compounds of formula I may also exist as tautomers.”

Although D1 published after the earliest claimed priority date of the ‘991 application (May 31, 2001), it claimed an earlier priority date (December 10, 1999). D1 was also filed in India and granted as Indian Patent No. IN 241773.

A first examination report was issued in the ‘991 application on March 13, 2008. Pfizer filed a reply and amended claims on January 27, 2009. The Examiner issued a hearing letter ordering the Applicant to attend a hearing on January 22, 2015. During the hearing, the Examiner raised a new objection that the claims were unpatentable under Section 3(d) of the India Patents Act 1970, as amended (Patent Act). Ultimately, the application was rejected. Pfizer appealed and on October 31, 2014, the Intellectual Property Appellate Board (IPAB) set aside the order and directed the IPO to reconsider the application.

On February 3, 2015, Pfizer submitted an amended claim set amending claim 1 as recited below and canceling the remaining claim (claim 2).

Amended claim 1:

  1. The compound 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof. 

In addition, Pfizer submitted copies of declarations of Dr. James D. Clark and Dr. Mark Edward Flanagan.

A hearing was held on January 22, 2015. The issues discussed were: (1) lack of novelty of claim 1 in view of D1; and (2) the unpatentability of claim 1 under Section 3(d) of the Patent Act.

During the hearing, Pfizer argued that D1 was not prior art and hence not novelty destroying because it was published after the priority date of the ‘991 application. With respect to the rejection of the claim under Section 3(d), Pfizer argued that this section was not applicable to the ‘991 application. Specifically, Pfizer argued that Section 3(d) applied to salts and isomers of a known substance. Although the rejected application was directed to an isomer, there was no known substance known to the public through a prior publication. Although D1 was filed earlier, it was not prior art. Therefore, because the compound of example 14 was a published after the priority date of the ‘991 application, it could not be considered a “known substance” for purposes of Section 3(d).

September 3, 2015 Decision by the Assistant Controller of Patents and Designs (Assistant Controller)

Regarding the novelty rejection, the Assistant Controller rejected Pfizer’s argument that D1 was not prior art. Specifically, the Assistant Controller referred to Section 13(1)(b) which refers to “anticipation by prior claiming” and states that “the invention is claimed in any claim of any other complete specification published on or after the date of filing of the applicant’s complete specification, being a specification filed in pursuance of an application for a patent made in India and date before or claiming the priority date earlier than that date”. The Assistant Controller noted that for the purpose of determining novelty, an application for a patent filed in the Indian Patent Office before the filing date of a complete specification of a later filed application but published later, is prior art for the purposes of “prior claiming”.

The Assistant Controller also noted that Pfizer was the applicant for both the ‘991 application and D1. Moreover, the Assistant Controller did not find any “distinctive” difference between the claimed compound and the compound disclosed in D1, noting that the compound claimed in the ‘991 was the enantiomer of the compound disclosed in D1. Additionally, the Assistant Controller stated that Pfizer failed to furnish comparative data distinguishing the features of the claimed compound over D1 (which was a similar compound). Instead, Pfizer provided comparative data of the four enantiomeric forms of the compound disclosed in D1 and published in 2008 in the Journal of Medicinal Chemistry (Journal), which, according to the Assistant Controller, was irrelevant.

Regarding the rejection under Article 3(d), the Assistant Controller referred to the decision in Novartis AG v/s Union of India (Civil Appeal Nos. 2706-2716 of 2013) which held that an applicant must establish the therapeutic enhanced efficacy of the claimed compound over a base compound. According to the Assistant Controller, Pfizer failed to provide experimental data demonstrating that 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile exhibited enhanced efficacy over the compound in D1 (namely, 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile). Instead, Pfizer submitted experimental data comparing the efficacy of the claimed compound with three other possible enantiomers disclosed in the Journal. No where did the Journal provide data demonstrating enhanced efficacy of the claimed compound with the compound disclosed in D1. Specifically, the Assistant Controller stated, “[T]he applicant is supposed to establish the enhancement of therapeutic efficacy of the specifically claimed form over D1 by substantive research data. They failed to provide such findings.”

The Assistant Controller concluded:

From the present amended claim 1, it can be concluded that the compound claimed in claim 1 is the enantiomer of compound of the cited document 1 and hence not novel and inventive as stated above. However, in absence of disclosure of any test result and comparative data over the base compound 3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile (compound in D1), I do not admit that the claimed compound has enhanced efficacy over the base compound in D1 and hence not patentable under Section 3(d) of Patents Act. The applicant’s contention that D1 can’t be the document to assess the patentability aspect of the invention claimed, since not known only to the public is not acknowledged.

After having considered the submissions submitted by the applicant in the hearing, the written submission and amended claims filed, in view of the above discussions and findings by me, it is hereby ordered that the invention disclosed and claimed in the instant application i.e., ‘3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof’ (amended claim 1 submitted on 30/01/2015) is not considered as an invention under the provisions of the Act as discussed above and I therefore, hereby refuse this Application No. 991/MUMNP/2003 to proceed further.

This post was written by Lisa Mueller and Nidhi Anand of Chadha & Chadha

Divisional Applications and the Patent Prosecution Highway Program between U.S. and Mexico

The Patent Prosecution Highway (PPH) Program between the Mexican Institute of Industrial Property (IMPI) and the United States Patent and Trademark Office (USPTO) was established as a permanent program on September 1, 2012. The object of this program is to accelerate the granting of Mexican applications that have a granted U.S. counterpart, having a common claim of priority, when both the Mexican and U.S. national phase applications derive from the same PCT application.

It is important to note that in order to request PPH examination in Mexico, the following issues should be considered:

  • The Mexican application must be published in IMPI’s gazette.
  • The request for PPH examination must be filed before the start of substantive examination.
  • At least one of the claims granted in the U.S. counterpart must be included in the Mexican application.
  • The PPH request must include a comparative table between the claims granted in the U.S. application and the claims pending in the Mexican application.

There is a practice in the Mexican Patent Office in which it is possible to request PPH examination for a parent application and, at the same time, request PPH examination for one or more divisional applications. In order for this to happen, the USPTO must have identified patentable matter in the claims of both the parent and the divisional application. In other words, in a single day, an applicant may file a PPH request for the parent case, a Mexican divisional(s) application(s) and a PPH request for the divisional(s) application(s). The reason this is possible is because divisional applications are not published in IMPI’s gazette until granted.

It is important to note that the above information is not contained in the guidelines for requesting participation in the PPH program at IMPI. This information has been generated according to Olivares’ experience in filing requests for PPH examination between USPTO and IMPI.

Requests for PPH examination are an attractive option for U.S. applicants because it is possible to obtain a Notice of Allowance for a corresponding Mexican application approximately 2 to 3 months after the PPH request is filed.

This post was written by Lisa Mueller, Mauricio Samano and Jose Luis Salgado of Olivares.

Update in Amgen v. Sandoz

On August 31, 2015, to support the launch of its Zarxio™ (a biosimilar of Amgen’s Neupogen® (filigrastim) product), Sandoz filed an opposition to Amgen’s emergency motion for injunction pending en banc consideration and review.  The opposition can be found here:  Sandoz opposition 08-31-2015 — 17703935 v1.

Sandoz argues that Amgen’s emergency motion should be denied since it does not meet the “applicable standard for such an injunction.”  Specifically, Sandoz alleges that Amgen cannot make a strong showing of a likelihood of success on the merits on its en banc petition, and that Amgen has not shown a likelihood of irreparable harm.  Further, Sandoz states that the balance of hardship weighs in Sandoz’s favor (as “any further injunction would seriously jeopardize the first-to-market advantage Sandoz earned”), and that the requested injunction would “disserve the public interest” by harming the interests of cancer patients and purchasers.  Moreover, Sandoz argues that Amgen’s own delay in seeking injunction on any alleged patent rights (despite having received Sandoz’s biosimilar application on February 9, 2015) precludes the equitable relief it seeks. The panel decision on July 21, 2015 maintains the injunction over the launch of Zarxio™ through September 2, 2015.

Today, a divided (2-1) Federal Circuit rejected Amgen’s bid to block sales of Sandoz’s Zarxio™ during continued litigation between the companies. Without any explanation, the Court denied Amgen’s request for a new injunction while the full Federal Circuit considers Amgen’s petition for en banc rehearing. As a result, this decision clears the way for the first biosimilar approved under the Biologics Price Competition and Innovation Act. In fact, sales of Zarxio™ may begin as early as tomorrow. A copy of the order can be found here:  order.

The BRIC Wall Blog will continue to monitor the ongoing litigation between Amgen and Sandoz as well as Sandoz’s launch of Zarxio™.

This post was written by Lisa Mueller and Wei Yan.

BRIC Wall Blog Nominated for “2015 Best Legal Blog Content”

The BRIC Wall blog has been nominated for The Expert Institute’s Best Legal Blog Contest. This year’s 250 finalists have been identified as the “most exciting, entertaining, and informative legal blogs online today,” by The Expert Institute, and the BRIC Wall Blog has been included as a leader in the Intellectual Property Category.

Readers can vote for the BRIC Wall Blog to be named the 2015 Best Legal Blog Content winner! To vote, please click here: https://www.theexpertinstitute.com/blog-category/intellectual-property/

Polls are open until Friday, October 9, 2015. Thank you for your support!