API and IP Newsletter

 Contents

• First Generic Approvals in 2023

• General information

• Pharmaceutical companies have $700 billion for acquisitions and investment

• Croda strengthens global position with Solus Biotech acquisition

• Intellectual Property

• T 1095/21 (Stabilized ACC/Amorphical) 14-06-2023

First Generic Approvals in 2023

FDA publishes list of first generic approvals. Recently such list for ANDA approvals till April 2023 is published. “First generics” are the first generic approval by FDA which permits a manufacturer to market a generic drug product in the United States.

No	Generic Name	ANDA Applicant	Approval Date	ANDA Indication
1	Nitisinone Capsules, 2 mg, 5 mg, 10 mg, and 20 mg	Torrent Pharma Inc.	09-Jan-23	For the treatment of adult and pediatric patients with hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine
2	Phenylephrine Hydrochloride Ophthalmic Solution USP, 10 %	Mankind Pharma Limited	11-Jan-23	For the purpose of dilating the pupils
3	Morphine Sulfate Injection USP, 2 mg/mL, 4 mg/mL, 8 mg/mL, 10 mg/mL, 15 mg/mL	Hikma Pharmaceuticals International Limited	12-Jan-23	For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate
4	Cysteine Hydrochloride Injection USP, 725 mg/10 mL (72.5 mg/mL)	Nivagen Pharmaceutical, Inc.	26-Jan-23	For use as an additive to amino acids solutions to meet nutritional requirements of newborn infants requiring total parenteral nutrition (TPN) and of adult and pediatric patients with severe liver disease who may have impaired enzymatic processes and require TPN
5	Tirofiban Hydrochloride Injection, 5 mg/100 mL (50 mcg/mL), Single-Dose Containers	Nexus Pharmaceutical, Inc.	07-Feb-23	To reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome
6	Topiramate Extended-Release Capsules, 200 mg	Zydus Pharmaceuticals (USA) Inc.	09-Feb-23	Initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 6 years of age and older; adjunctive therapy for the treatment of partial-onset, primary generalized tonic-clonic seizures or seizures associated with Lennox-Gastaut syndrome (LGS) in patients 6 years of age and older; preventive treatment of migraine in patients 12 years of age and older
7	Doxepin Hydrochloride Cream, 5%	Teva Pharmaceuticals Development, Inc.	17-Feb-23	For the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus
8	Tiopronin Delayed-Release Tablets, 100 mg and 300 mg	Par Pharmaceutical, Inc.	24-Feb-23	For the prevention of cystine stone formation in adults and pediatric patients 9 years of age and older with severe homozygous cystinuria, who are not responsive to these measures alone
9	Acetaminophen and Ibuprofen Tablets, 250 mg/125 mg (OTC)	L. Perrigo Company	28-Feb-23	Temporarily relieves minor aches and pains due to headache, toothache, backache, menstrual cramps, muscular aches, minor pain of arthritis
10	Bismuth Subcitrate Potassium, Metronidazole & Tetracycline Hydrochloride Capsules, 140 mg/125 mg/125 mg	Par Pharmaceutical, Inc.	06-Mar-23	For the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori
11	Tofacitinib Tablets, 5 mg and 10 mg	Micro Labs Limited	13-Mar-23	For the treatment of adult patients with moderately to severely active rheumatoid arthritis; active psoriatic arthritis; moderately to severely active ulcerative colitis
12	Calcipotriene and Betamethasone Dipropionate Foam, 0.005%/0.064%	Glenmark Pharmaceuticals Limited	21-Mar-23	For the topical treatment of plaque psoriasis in patients 12 years and older
13	Tenofovir Alafenamide Tablets, 25 mg	Lupin Limited	30-Mar-23	For the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease
14	Budesonide Rectal Foam, 2 mg/dose	Padagis Israel Pharmaceuticals Ltd.	12-Apr-23	For the induction of remission in patients with active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge
15	Loteprednol Etabonate Ophthalmic Suspension, 0.2%	Akorn Operating Company LLC	12-Apr-23	For the temporary relief of the signs and symptoms of seasonal allergic conjunctivitis
16	Estradiol Transdermal System USP, 0.014 mg/day	Zydus Noveltech, Inc	17-Apr-23	For the prevention of postmenopausal osteoporosis
17	Midazolam in 0.9% Sodium Chloride Injection, 50 mg/50 mL (1mg/mL) and 100 mg/100 mL (1 mg/mL) Single-Dose Bags	Hikma Pharmaceuticals USA Inc.	17-Apr-23	Continuous intravenous infusion for sedation of intubated and mechanically ventilated adult, pediatric, and neonatal patients as a component of anesthesia or during treatment in a critical care setting
18	Thalidomide Capsules USP, 50 mg, 100 mg, 150 mg, 200 mg	Natco Pharma Limited	27-Apr-23	For the treatment of patients with newly diagnosed multiple myeloma; for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL); as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence

Certain ANDAs are deemed “first generic” for the purposes of review prioritization. In this context, a first generic application is any received ANDA: (1) That is a first-to-file ANDA eligible for 180-day exclusivity, or for which there are no blocking patents or exclusivities; and (2) for which there is no previously-approved ANDA for the drug product.

One could notice there are 5 Indian companies sought first generic approval out of total 18 approvals till April 2023.

General information

Pharmaceutical companies have $700 billion for acquisitions and investment

The global pharmaceutical sector has around $700 billion at its disposal to acquire other companies and invest in research and development, according to Goldman Sachs Research. That war chest will be important as patents expire for some of the industry’s blockbuster drugs.

News here.

Croda strengthens global position with Solus Biotech acquisition

Croda International Plc (Croda), a global specialty chemicals company, has completed the acquisition of Solus Biotech from Solus Advanced Materials, expanding its biotechnology capabilities and presence in Asia. Solus Biotech, a leader in premium biotechnology-derived materials, brings valuable technologies in biotech-derived ceramide and phospholipids to Croda’s portfolio. Located in South Korea, this expands Croda’s Asian manufacturing capability further and will create a new biotechnology R&D hub in the region.

News here

Intellectual Property 

T 1095/21 (Stabilized ACC/Amorphical) 14-06-2023

This case is regarding EP 2882687. This patent titled Method for producing stabilized amorphous calcium carbonate and is issued to Amorphical Ltd. 

Schaefer Kalk GmbH & Co. opposed it. The first instance, i.e..  Opposition Division at EPO upheld the patent.  Schaefer Kalk GmbH appealed. The matter was heard before Board of Appeals at European Patent Office (EPO).

 

Claim 1 of the patent EP 2882687 reads as follows:

"1. A method of preparing amorphous calcium carbonate (ACC), comprising the steps of:

i) combining an aqueous solution comprising a soluble calcium salt and a first stabilizer with an aqueous solution comprising a soluble carbonate so as to form an ACC suspension; and

ii) adding a water miscible organic solvent and a solution comprising a second stabilizer, simultaneously or sequentially in any order so long as said second stabilizer and organic solvent contact said ACC suspension within 2 minutes of its formation, thereby obtaining a stabilized suspension of ACC;

wherein the first stabilizer and the second stabilizer are the same or different; and wherein the total amount of the stabilizer constitutes up to 12 wt% of the stabilized ACC suspension, and the water miscible organic solvent constitutes at least 5 wt% of the stabilized ACC suspension."

Claims 2 to 11 directly refer to claim 1.

There are couple of other independent claims and more arguments about novelty and added subject matter. We will discuss in this write-up inventive step arguments for claims 1 to 11. 

Following documents cited as prior art:

D1: S. Bentov et al., Journal of Structural Biology, 207-15

D3: CA 2 806 131

D14: G.B. Cai et al., CrystEngComm, 12, 2010, 234-41

The board decided this invention meets the inventive step requirements of Article 56 of EPC 

The reasons are as follows.

1. The invention relates to a process for preparing ACC.

2. In agreement with the parties, D3 and the process of example 1 is considered the closest prior art.

3. The alleged problem to be solved is to provide a process leading to an ACC with increased stability.

4. The proposed solution to this problem is a process according to claim 1 characterised at least in that a water miscible organic solvent and a solution comprising a second stabiliser are added to the ACC suspension within two minutes of its formation, thus obtaining a stabilised suspension of ACC in which the total amount of the stabiliser constitutes up to 12 wt% of the stabilised ACC suspension and the water miscible organic solvent constitutes at least 5 wt% of the stabilised ACC suspension.

5. The product of example 1 of prior art D3 is stable for at least five days. 

6. There is no direct comparison of the process according to claim 1 of the patent with the exact process of example 1 of D3, which would prove that the process stability of the claimed product is superior. 

7. The other prior art documents too do not include the exact process of D3 but a change of stabiliser. Furthermore, experimental details are rather limited in other cited prior arts. 

8. Therefore, the problem needs to be redefined in less ambitious terms as the provision of an alternative process for producing a stable ACC product.

9. The solution to the problem is not obvious for the following reasons.

10. The prior art D3 discusses when the stabiliser should be added. It discloses that it should be added most preferably at least five minutes after the reactants are mixed (page 15, fourth line from bottom). 

11. It is not credible that the skilled person would consider doing the addition within two minutes considering that the addition in example 1 of D3 was only done after 14.75 minutes. 

12. Furthermore, D3 is completely silent about the addition of part of the stabiliser in a second step. This teaching is also not available from the many documents cited by the appellant Schaefer Kalk GmbH. 

13. The Board stated, to argue that the skilled person would contemplate this addition is based on hindsight. Therefore, the board concurs with the opposition division's conclusion since at least this second process step is not obvious in view of the prior art.

Consequently, the subject-matter of claim 1 and claims 2 to 11 involve an inventive step.

Decision here