API and IP Newsletter
Contents
CDSCO New Drugs Approvals
CDSCO publishes the list of new approvals.
Recently the of List of New Drugs approved in the year 2023 till date is published. It is updated till July 2023. This year, till July 2023, 21 new drugs are approved. List is here. In this link one would notice, name of MA holder is not mentioned. One must search somewhere else at the same CDSCO site or search in public domain for an educated guess.
New drugs as define under Rule 122-E of Drugs and Cosmetics Rules include unapproved drugs, modified or new claims, namely, indications, dosage forms (including sustained release dosage form) and route of administration of already approved drugs and combination of two or more drugs
In this write-up we are covering drugs approved in May-June and July 2023.
General information
Johnson & Johnson is replacing its iconic logo
Johnson & Johnson is replacing its instantly recognizable logo that’s been in use for 135 years.
Gone is the cursive, which was based off the handwritten signature of company co-founder James Wood Johnson, and in its place is the name written in modernized font as the newly spun-off company focuses on medical devices and medications.
News here.
US FDA to seek public opinion before banning popular cough syrup ingredient
The U.S. Food and Drug Administration said on Thursday it would seek public opinion before finalizing its decision to remove a decongestant widely used in cough syrups from the agency's list of ingredients for over-the-counter (OTC) use.
The FDA's clarification follows a unanimous vote by its panel of outside experts on Tuesday against the effectiveness of oral OTC medicines made with phenylephrine, an ingredient widely used in cold and cough syrups.
News here
Intellectual Property
BMS has been accused of using fraudulent patents and other illegal tactics for Pomalyst
Bristol Myers Squibb has been accused in a new lawsuit of using fraudulent patents and other illegal tactics to maintain its monopoly on blockbuster blood cancer drug Pomalyst for years after it should have faced generic competition. The complaint was filed by Louisiana Health Service & Indemnity Company.
Natco, Teva, Aurobindo and Eugia are other defendants.
Patents in complaint are owned by Celgene. Bristol Myers Squibb took over Celgene in 2019.
Louisiana accused Bristol-Meyers Squibb and Celgene of patent fraud, alleged the firm misrepresented and hidden data about Pomalyst’s properties, formulations, and uses.
The lawsuit also contends that Bristol-Meyers Squibb and Celgene abused the federal judicial system by launching “sham lawsuits” against generic companies trying to enter the U.S. market for pomalidomide, which is the generic formulation sold under the brand name Pomalyst.
BMS and Co have been accused of anti-competitive practices, including paying off competitors to drop legal challenges to pomalidomide patents.
Louisiana alleged, there are several fraudulent submissions to patent office for various OB listed and non-OB listed patents. Some of those are mentioned in this article.
During the prosecution of OB US 8,198,262 (’262) patent, the PTO focused on whether the prior art taught pomalidomide or taught treating multiple myeloma. Prior art D’Amato (2001) teaches not just one, but both, of these critical points. This fact appears to have been lost on the PTO (Patent Office), likely due to confusion regarding nomenclature (the study refers to pomalidomide as 3-aminothalidomide instead of 4-aminothalidomide)
Patent applicant/inventors of Celgene Dr. Zeldis, Mr. Insogna, and Ms. Moon knew this material information, but fraudulently omitted to disclose the truth about D’Amato (2001) to the PTO because it undermined the patentability of the claimed invention.
Dr. Zeldis, Mr. Insogna, and Ms. Moon submitted to the PTO a “List of Referenced Cited by the Applicant,” which included D’Amato (2001).
The ’262 patent application and D’Amato (2001) included diagrams that made clear the application and D’Amato (2001) were referring to the same compound.
First, Celgene misrepresented that the treatment of multiple myeloma with pomalidomide had not been publicly disclosed previously. That was knowingly false.
Second, Celgene misrepresented that the use of one thalidomide compound over another had not been publicly disclosed previously. That was knowingly false.
Third, Celgene misrepresented that pomalidomide combined with dexamethasone produced unexpected results for treating relapsed or refractory multiple myeloma patients. That was knowingly false, as there was nothing surprising about these results.
In short, Celgene’s response to PTO was intended to deceive the examiner into withdrawing prior rejections, having the examiner not appreciate the full prior public disclosures regarding the potential to treat multiple myeloma using pomalidomide, and to believe the ostensible unexpected results were a lawful basis to allow the claims
On February 8, 2017, at least seven generic manufacturers (Teva, Natco/Breckenridge, Apotex, Hetero, Par, Aurobindo, and Mylan) filed ANDAs to market generic Pomalyst. At least nine ANDAs have been filed to date.
On May 4, 2017, Celgene filed its first Pomalyst patent infringement lawsuit. The suit, against Par and Teva, alleged infringement of four patents. On May 11, 2017, Celgene sued Hetero, Aurobindo/Eugia, Apotex, Mylan, and Natco/Breckenridge, for infringement of the same patents:
8,198,262 Method of treatment
8,673,939 Method of treatment
8,735,428 Method of treatment
In another alleged fraudulent act, in the Spring of 2018, Celgene pursued a formulation patent (the ’5939) through fraud. Celgene’s quest to acquire additional Pomalyst patents to block generic competition continued unabated.
On May 10, 2018, Celgene filed application no. 15/976,808. Celgene filed this patent application more than a year after receiving seven paragraph IV letters describing in detail the ANDA products those generic manufacturers sought to bring to market:
One more alleged wrong practice was in late 2018 to early 2019, the Celgene obtained the polymorph patents and promptly filed new sham litigation as to those three patents.
On October 9, 2018, the three polymorph patents (the ’647, ’648, and ’649) issued. Celgene had not even applied for the polymorph patents until months after receiving the ANDA filers’ paragraph IV letters.
Celgene nevertheless promptly filed new lawsuits against the generic manufacturers alleging infringement of the newly issued polymorph patents (‘647, 648, and ‘649):
According to the complaint Louisiana Health Service, this is not right business practice to sue on later OB listed polymorph patents.
Celgene’s claims of infringement were doomed from the start by a catch-22 of Celgene’s own making: if an earlier-in-time ANDA product would infringe one of Celgene’s later-intime polymorph patents, then the patent is invalid as anticipated and/or obvious in light of the prior art.
Earlier, on July 24, 1996, Celgene filed patent application no. 08/690,258, which led to the 5,635,517 (the “’517 patent”).
The ’517 patent identified analogs of thalidomide, including lenalidomide and pomalidomide, as compounds decreasing TNFα levels.
As the ’517 patent explains, “decreasing TNFα levels . . . constitutes a valuable therapeutic strategy for the treatment of many inflammatory, infectious, immunological or malignant diseases. . . . These include but are not limited to . . . cancer . . . .”
The ’517 patent also claimed the compound lenalidomide, an analog to thalidomide (having one fewer oxygen atom and one more nitrogen atom), and method of using lenalidomide to reduce undesirable levels of TNFα. (The ’517 patent would later become the foundation of Celgene’s Revlimid franchise, earning it $35 billion in the U.S. in the last five years alone. Revlimid, in combination with the steroid dexamethasone, is used primarily in the treatment of multiple myeloma).
As Teva (Natco’s Revlimid marketing partner) described it: with its Revlimid settlements, Celgene set up a “profit share.”
The royalty-free generic license prior to true generic competition constitutes a large reverse payment from Celgene to the generic that equates to hundreds of millions of dollars in the first year of generic sales alone.
And the most-favoured entry clause deters other generics from continuing to challenge Celgene’s patents and provides assurance to Natco that it will receive the most favourable entry date and retain its lucrative exclusivity period.
It was alleged in the complaint that Celgene would continue this pattern with other generics, engaging in a series of payoffs to would-be lenalidomide competitors. In the lenalidomide settlements, Celgene’s payoffs took the form of market allocation agreements in which Celgene sequentially granted small, volume limited licenses to each generic company to sell lenalidomide starting in 2022 and going to early 2026 (at which time there would be unconstrained competition). The volume-limited license agreements, which also contain no royalties to Celgene, significantly reduce the extent of price reduction and effectively allocate the market amongst competitors
In short, Celgene and Natco worked anticompetitive arrangements in the past by settling patent litigation and did so with respect to a product used in a complementary way to treat the same conditions. The date for bona fide agreed entry in the lenalidomide settlement is the first quarter of 2026, the same quarter to which the pomalidomide Celgene-Natco agreement delays pomalidomide entry. And Celgene is a repeat offender in reaching anticompetitive, market allocation agreements in the same period it reached the Celgene-Natco agreement.
The facts surrounding the disclosure of the settlement also show that the Celgene-Natco agreement contains an anticompetitive reverse payment.
Nearly all the generics that had a Pomalyst ANDA also had a Revlimid ANDA. After being sued by Celgene for infringement of Celgene’s Pomalyst and Revlimid patents, a generic often settled the two matters concurrently.
Summary:
Thus there are lot of allegations in 151 pages complaint by Louisiana. We covered very few in this write-up.
There are allegations for reverse payments to, and market allocation with, would-be competitors.
In summary, Louisiana said in the complaint that BMS and others violated U.S. antitrust law and had caused purchasers of the drug to overpay "by many hundreds of millions, if not billions, of dollars."
The anticompetitive reverse payment settlements occurred in the wake of Celgene’s litigations against the would-be generic competitors.
Now acquired by Bristol Myers and knowing that Celgene would not prevail in the patent litigation, Celgene and Bristol Myers paid off at least several of the first-to-file generic companies including Aurobindo, Eugia, Breckenridge, Natco, and Teva to have each discontinue its challenge to the pomalidomide patents and delay their entry into the U.S. market.
While the form of the payment is cloaked under an effort at absolute secrecy, each of the reverse payment agreements include a payment well into nine figures, and each vastly exceeds the net revenues any one of the generic companies could hope to earn even if it had prevailed in the patent litigation.
Each also allocates the pomalidomide market. Had Celgene and Bristol Myers not paid off their would-be competitors, generic pomalidomide would have been available sooner than it will be.
Complaint here
