Two Prostate Cancer Drugs in One Tablet A Claim Set Narrower Than Its Title

This application covers combining two prostate cancer drugs, abiraterone acetate and niraparib, into a single tablet and giving it alongside a steroid. The title and the abstract talk about prostate cancer in general, but claim 1 does not. It is limited to one stage of the disease, metastatic castration-sensitive prostate cancer, and it requires a specific salt form of niraparib and mandatory co-administration of prednisone. The applicant is Janssen Pharmaceutica NV, the Belgian arm of Johnson and Johnson’s pharmaceutical business, and the application is a divisional of Australian application 2021267146.

The Problem

Prostate cancer grows on androgens. The specification sets out the usual sequence: localised disease is often curable with surgery or radiotherapy, but local therapy fails in up to a third of men, and the disease then spreads. The first systemic response is to take the androgens away, which is androgen deprivation therapy, delivered either as drugs or as surgical castration. While the tumour still responds to that, it is called castration-sensitive. When it learns to grow despite castrate testosterone levels, it is called castration-resistant, and the specification lists the options at that point as taxane chemotherapy and androgen receptor targeted drugs such as apalutamide and enzalutamide.

Abiraterone acetate attacks the same axis from a different angle. It blocks an enzyme the body uses to make androgens, cutting supply from the testes, the adrenal glands and the tumour itself. Because that enzyme also sits on the pathway to cortisol, blocking it drives up a hormone that causes fluid retention, high blood pressure and low potassium, which is why abiraterone is always given with a corticosteroid. The specification notes that abiraterone plus prednisone had been approved for metastatic castration-resistant disease.

Niraparib comes from a different direction entirely. It is an oral PARP inhibitor active against PARP-1 and PARP-2, and the specification explains the mechanism in a few sentences. PARP enzymes repair single-strand breaks in DNA. Inhibit them and the breaks accumulate, replication forks stall and collapse, and single-strand damage becomes double-strand damage. Healthy cells fix double-strand breaks by homologous recombination. Tumour cells carrying a fault in that repair machinery cannot, so they die while normal cells survive. The specification states that cancers with DNA repair anomalies account for roughly 20 to 30 per cent of sporadic cancers.

The practical problem the formulation work addresses is mundane and specific. Abiraterone acetate is dosed at 1000 mg a day and niraparib at 200 mg, and the two were supplied as separate products, tablets and capsules, made by different processes. Getting both actives into one tablet that releases them properly is the engineering task the examples document.

What This Invention Does

Claim 1 is a product claim written in the European “combined preparation for use” style rather than as a method. It reads on a pharmaceutical formulation comprising abiraterone acetate and niraparib tosylate monohydrate, as a combined preparation for simultaneous, separate or sequential use with prednisone, in treating mCSPC, optionally where the mCSPC is deleterious germline or somatic homologous recombination repair gene-mutated mCSPC, in a male human patient.

Four limitations in that sentence are worth pulling out, because the title conceals all of them.

The disease is restricted. Claim 1 covers metastatic castration-sensitive prostate cancer only. The body of the specification lists a dozen disease states as objectives of the invention, including metastatic castration-resistant disease, non-metastatic castration-resistant disease, biochemical recurrence and localised prostate cancer. None of those is claimed here. That matters because the castration-resistant setting is the one the combination was first approved in, and it is the subject of Example 7 of this very document.

The salt form is fixed. Claim 1 requires niraparib tosylate monohydrate, not niraparib free base. The salt factor is stated as 1.594, so 79.70 mg of the tosylate delivers 50 mg of niraparib.

Prednisone is mandatory. The formulation is claimed as a combined preparation for use with prednisone, so a tablet given without the steroid falls outside claim 1.

The gene mutation is optional. The HRR-mutated subgroup is introduced by the word “optionally”, so claim 1 covers castration-sensitive metastatic disease whether or not the tumour carries a repair gene fault. Claim 2 lists the genes when the option is taken: BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD51B and RAD54L.

Claims 2 to 19 narrow the patient’s prior treatment history, then split the product into a free-dose combination, where the two drugs are taken as separate units, and a fixed-dose combination in one tablet. Claim 16 sets out the eight strength pairs contemplated: 50 or 100 mg of niraparib equivalent with 500 mg, 375 mg or 250 mg of abiraterone acetate, and 33 or 67 mg of niraparib equivalent with 333 mg of abiraterone acetate. Claims 20 to 39 repeat the whole structure as method of treatment claims, still limited to mCSPC.

The examples are formulation work. The lead tablet in Table 1 is a 1500 mg core containing 500 mg of abiraterone acetate and 79.70 mg of niraparib tosylate monohydrate, wet granulated with a hypromellose and sodium lauryl sulfate binder solution, with lactose monohydrate and crospovidone inside the granule and silicified microcrystalline cellulose, more crospovidone, more sodium lauryl sulfate, colloidal silica and magnesium stearate outside it. Film coating takes it to 1560 mg. The higher strength in Table 3 is a 1600 mg core with 159.40 mg of the tosylate, coated to 1664 mg.

The manufacturing data are specific. For the Table 1 composition, five samples gave average tablet weights of 1502.7 to 1506.6 mg, thickness 7.80 to 7.83 mm, hardness 265 to 273 N, and disintegration times of 2 minutes 51 seconds to 3 minutes 12 seconds. The Table 3 tablets ran harder, 306 to 330 N, and took 3 minutes 2 seconds to 4 minutes 27 seconds to disintegrate. Content uniformity for the Table 3 composition averaged 101.32 per cent for abiraterone acetate and 102.18 per cent for niraparib tosylate, with relative standard deviations of 1.91 and 2.03 per cent. Example 5 reports no degradation of either active in the dried granules, with oxidative degradants of abiraterone acetate within specification after 12 months at 5 degrees C, 25 degrees C at 60 per cent relative humidity and 30 degrees C at 75 per cent relative humidity, and after 6 months at 40 degrees C at 75 per cent relative humidity.

Examples 7 and 8 are clinical trial protocols, not results. Example 8 is the AMPLITUDE study in castration-sensitive disease, the setting claim 1 is drawn to: roughly 788 participants randomised one to one to niraparib 200 mg plus abiraterone acetate 1000 mg plus prednisone 5 mg daily, or abiraterone acetate 1000 mg plus prednisone 5 mg daily, everyone on background androgen deprivation, with radiographic progression-free survival as the primary endpoint. The specification prints the objectives, the inclusion and exclusion criteria and the endpoint definitions. It reports no outcome data at all.

Key Features

• A single tablet carrying two different oncology drugs. The fixed-dose combination puts an androgen synthesis blocker and a DNA repair inhibitor into one 1500 or 1600 mg core tablet, replacing a tablet plus capsule regimen.
• Claim 1 is limited to castration-sensitive disease. Despite a title that says “prostate cancer” and a body that lists a dozen disease states, every independent claim in this divisional is confined to metastatic castration-sensitive prostate cancer.
• Prednisone written into the claim. The formulation is claimed as a combined preparation for simultaneous, separate or sequential use with prednisone, reflecting the fact that blocking androgen synthesis also disrupts cortisol production.
• A named salt and hydrate, not the free base. Claim 1 requires niraparib tosylate monohydrate. At the stated salt factor of 1.594, 79.70 mg of tosylate gives 50 mg of niraparib and 159.40 mg gives 100 mg.
• Three alternative manufacturing routes. Example 2 wet granulates both actives together, Example 3 dry granulates the niraparib separately and blends it with fluid bed granulated abiraterone, and Example 4 dry granulates the two actives as co-granules. All three end in compression and film coating.
• Eight strength pairs and a defined dissolution method. Claims 16 and 36 list the niraparib to abiraterone ratios contemplated, and Example 6 fixes the release test: USP paddle apparatus, 900 mL of 0.25 per cent sodium lauryl sulfate in 0.05 M phosphate buffer at pH 4.5, 75 rpm, analysed by UHPLC with UV detection at 236 nm.

Who Is Behind It

Janssen Pharmaceutica NV is the Belgian research company founded by Paul Janssen in 1953, now part of Johnson and Johnson Innovative Medicine. The inventor list on the title page splits cleanly into two groups. Thomas Ronald A. Quinten, Urbain Alfons C. Delaet, Philip Erna H. Heyns, Tatiana Marcozzi, Johny Bertels, Katrien Luyten, Kaustubh Ramesh Tambwekar and Paul J. A. Hartman Kok are formulation and process people, which matches the granulation, blending and tabletting content of Examples 1 to 6. Angela Lopez-Gitlitz is the clinical name, matching the trial protocols in Examples 7 and 8.

The commercial context sits outside the document. In August 2023 the United States Food and Drug Administration granted accelerated approval to a fixed-dose combination of niraparib and abiraterone acetate, marketed as Akeega, with prednisone, for adults with BRCA-mutated metastatic castration-resistant prostate cancer. The approved dose is 200 mg of niraparib with 1000 mg of abiraterone acetate once daily plus 10 mg of prednisone. That is the castration-resistant setting, which this divisional does not claim. The claims here reach the earlier, castration-sensitive stage, which is the subject of the AMPLITUDE trial written into Example 8 and which reported positive progression-free survival results in 2025, four years after the priority date and well after the parent application was filed.

On priority the specification is explicit. The opening paragraph states that the application is a divisional of Australian application 2021267146, itself the national phase entry of PCT/EP2021/062186, which claims priority from United States provisional applications 63/142,919 filed 28 January 2021 and 63/174,282 filed 13 April 2021, and European provisional application 20173749.1 filed 8 May 2020. The earliest of those is the European filing in May 2020.

Why It Matters

The interesting thing about this application is the gap between what it is called and what it claims. Anyone reading the title, “Treatments of prostate cancer with combinations of abiraterone acetate and niraparib”, would expect coverage of the combination across the disease. Anyone reading the abstract, which promises free-dose and fixed-dose combinations and methods of treating prostate cancer, would expect the same. The claims deliver something much narrower: one disease stage, one salt form, one mandatory companion drug. Divisionals are often filed precisely to carve out a slice of subject matter left over from the parent, and reading only the front page of one of these documents will mislead you about its scope.

The second point is that combining two approved drugs into one tablet is not a trivial exercise, and the examples show why it took a team of eight formulators. Abiraterone acetate is poorly soluble and is dosed at five times the daily milligram load of its partner, and ten times it in the lower strength tablet, which is why every formulation in this document needs a wetting agent inside and outside the granule and why the finished tablets weigh a gram and a half. The three different granulation routes in Examples 2, 3 and 4 read like a record of trying to get one process to handle two actives with very different behaviour.

Finally, the clinical logic behind the claim is worth understanding even though the document does not argue it. PARP inhibitors were built for tumours that cannot repair double-strand DNA breaks, which is why the gene list in claim 2 exists. Adding one to androgen blockade earlier in the disease, while the tumour is still castration-sensitive, is a bet that hitting both the hormone supply and the repair machinery before resistance develops will hold the disease back longer than treating them in sequence. Whether that bet pays off is not something this specification attempts to show. It sets out the protocol and stops.

Related Concepts

• Synthetic lethality – the principle that makes PARP inhibition selectively kill repair-deficient tumour cells.
• CYP17A1 – the androgen synthesis enzyme abiraterone blocks, and the reason prednisone has to be given with it.
• BRCA2 – the best known of the repair genes listed in claim 2 and the basis of the approved indication in castration-resistant disease.
• Granulation – the powder processing step the examples run three different ways to get both actives into one tablet.
• Dissolution testing – the in vitro release measurement Example 6 specifies for comparing the combination tablet against the separate products.

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AU 2026202227 was published in the Australian Official Journal of Patents on 9 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.