Keytruda Qlex (pembrolizumab; berahyaluronidase alfa-pmph)

BL 761467

Keytruda Qlex (pembrolizumab; berahyaluronidase alfa-pmph)

BL 761467

U.S. License Holder:

Merck Sharp Dohme

Date of License:

September-19-2025

Last Update:

Sep-30-2025

approved_indications FDA-Approved Indications

KEYTRUDA QLEX (pembrolizumab; berahyaluronidase alfa-pmph) is a combination of pembrolizumab, a programmed death receptor-1 (PD-1)-blocking antibody, and berahyaluronidase alfa, an endoglycosidase, indicated:

Melanoma: for the treatment of adult patients with unresectable or metastatic melanoma; for the adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection;

Non-Small Cell Lung Cancer (NSCLC): in combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations; in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of adult patients with metastatic squamous NSCLC; as a single agent for the first-line treatment of adult patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) greater than or equal to 1 percent] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberations, and is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic; as a single agent for the treatment of adult patients with metastatic NSCLC whose tumors express PD-L1 (TPS greater than or equal to 1 percent) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA QLEX; for the treatment of adult patients with resectable (tumors greater than or equal to 4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a greater than or equal to 4 cm), II, or IIIA NSCLC;

Malignant Pleural Mesothelioma (MPM): in combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with unresectable advanced or metastatic MPM;

Head and Neck Squamous Cell Cancer (HNSCC): In combination with platinum and FU for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC; As a single agent for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) greater than or equal to 1] as determined by an FDA-approved test; As a single agent for the treatment of adult patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy;

Urothelial Cancer: in combination with enfortumab vedotin, for the treatment of adult patients with locally advanced or metastatic urothelial cancer; as a single agent for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: are not eligible for any platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant treatment with platinum-containing chemotherapy; as a single agent for the treatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy;

Microsatellite Instability-High or Mismatch Repair Deficient Cancer: for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options;

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC): for the first-line treatment of adult patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test;

Gastric Cancer: in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS greater than or equal to 1) as determined by an FDA-approved test; In combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS greater than or equal to 1) as determined by an FDA approved test;

Esophageal Cancer: for the treatment of adult patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either: in combination with platinum- and fluoropyrimidine-based chemotherapy, for patients whose tumors express PD-L1 (CPS greater than or equal to 1), or s a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS greater than or equal to 10) as determined by an FDA-approved test;

Cervical Cancer: In combination with chemoradiotherapy, for the treatment of adult patients with locally advanced cervical cancer involving the lower third of the vagina, with or without extension to pelvic sidewall, or hydronephrosis/nonofunctioning kidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA); in combination with chemotherapy, with or without bevacizumab, for the treatment of adult patients with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 (CPS greater than or equal to 1) as determined by an FDA-approved test; as a single agent for the treatment of adult patients with recurrent or metastaticcervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS greater than or equal to 1) as determined by an FDA-approved test;

Hepatocellular Carcinoma (HCC): for the treatment of adult patients with HCC secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen;

Biliary Tract Cancer (BTC): In combination with gemcitabine and cisplatin, for the treatment of adult patients with locally advanced unresectable or metastatic biliary tract cancer;

Merkel Cell Carcinoma (MCC): for the treatment of adult and pediatric patients 12 years and older with recurrent locally advanced or metastatic Merkel cell carcinoma;

Renal Cell Carcinoma (RCC): In combination with axitinib, for the first-line treatment of adult patients with advanced RCC; In combination with lenvatinib, for the first-line treatment of adult patients with advanced RCC; For the adjuvant treatment of adult patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions;

Endometrial Carcinoma: In combination with carboplatin and paclitaxel, followed by KEYTRUDA QLEX as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma; In combination with lenvatinib, for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; As a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation;

Tumor Mutational Burden-High (™B-H) Cancer: For the treatment of adult and pediatric patients 12 yeears and older with unresectable or metastatic tumor mutational burden-high (™B-H) [greater than or equal to 10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options;

Cutaneous Squamous Cell Carcinoma (cSCC): For the treatment of adult patients with recurrent or metastatic cSCC or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer (TNBC): For the treatment of adult patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery; In combination with chemotherapy, for the treatment of adult patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS greater than or equal to 10) as determined by an FDA approved test.

approved_indications Inter Partes Review Proceedings

PTAB Portal

IPR Case No(s):

PGR2025-00003

U.S. Patent No.
11,952,600 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-4, 7-21

Claim Types Challenged Under § 103
Composition of Matter Other (Vector, Host Cell) Formulation Method of Treatment Manufacturing

§ 103 Challenge Instituted
Y: Claims 1-4, 8-21; Disclaimed Claim 7

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 5-7 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-21) and Enablement (Claims 1-21). Claims 5-7 Disclaimed Prior to Institution Decision. Instituted; Pending, Director Review of Institution Decision Denied

PGR2025-00004

U.S. Patent No.
12,018,298 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-4, 7-22

Claim Types Challenged Under § 103
Composition of Matter Other (Vector, Host Cell) Formulation Method of Treatment Manufacturing

§ 103 Challenge Instituted
Y: Claims 1-4, 7-19, 22; Disclaimed Claims 20-21

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 5-6, 20-21 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-22) and Enablement (Claims 1-22). Claims 5-6, 20-21 Disclaimed Prior to Institution Decision. Instituted; Pending, Director Review of Institution Decision Denied

PGR2025-00006

U.S. Patent No.
12,152,262 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-4, 7-13

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Y: Claims 1-4, 8-13; Disclaimed Claim 7

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 5-7 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-13) and Enablement (Claims 1-13). Claims 5-7 Disclaimed Prior to Institution Decision. Instituted; Pending, Director Review of Institution Decision Denied

PGR2025-00009

U.S. Patent No.
12,123,035 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-34

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Y: Claims 1, 2, 6-14, 16-29; Disclaimed Claims 5, 15, 30-34

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-5, 15, 30-34 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-34) and Enablement (Claims 1-34). Claims 3-5, 15, 30-34 Disclaimed Prior to Institution Decision. Instituted; Pending, Director Review of Institution Decision Denied

PGR2025-00017

U.S. Patent No.
12,110,520 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-35

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Y: Claims 1, 2, 6-15, 17-30; Disclaimed Claims 5, 16, 31-35

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-5, 16, 31-35 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-35) and Enablement (Claims 1-35). Claims 3-5, 16, 31-35 Disclaimed Prior to Institution Decision. Instituted; Pending

PGR2025-00024

U.S. Patent No.
12,060,590 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-35

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-5, 16, 31-35 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-35) and Enablement (Claims 1-35). Claims 3-5, 16, 31-35 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00030

U.S. Patent No.
12,054,758 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-6, 8, 10-40

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment Other (Method of Delivery)

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-5, 31-40 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-40) and Enablement (Claims 1-40). Claims 3-5, 31-40 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00033

U.S. Patent No.
12,049,652 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-40

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-5, 30-40 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-40) and Enablement (Claims 1-40). Claims 3-5, 30-40 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00039

U.S. Patent No.
12,104,185 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-11

Claim Types Challenged Under § 103
Method of Treatment

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 5-6 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-11) and Enablement (Claims 1-11). Claims 5-6 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00042

U.S. Patent No.
12,037,618 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 4-5, 7-22, 24-40

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-4, 6, 34-40 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-40) and Enablement (Claims 1-40). Claims 3-4, 6, 34-40 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00046

U.S. Patent No.
12,091,692 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 4-5, 7-26, 29-40

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 3-4, 6, 34-40 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-40) and Enablement (Claims 1-40). Claims 3-4, 6, 34-40 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00050

U.S. Patent No.
12,077,791 (Ph20 Polypeptide Variants with a Modification at Position 309 of the Ph20 Polypeptide and a Method of Making Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
N

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part-Claims 4-5 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-10) and Enablement (Claims 1-10). Claims 4-5 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

PGR2025-00052

U.S. Patent No.
12,264,345 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-17

Claim Types Challenged Under § 103
Composition of Matter Formulation

§ 103 Challenge Instituted
Awaiting Institution Decision

IPR Status
Challenges Also Include Written Description (Claims 1-17), Enablement (Claims 1-17), and Indefiniteness (Claims 1-17). Awaiting Institution Decision

PGR2025-00053

U.S. Patent No.
12,195,773 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Patent Owner
Halozyme, Inc.

Petitioner(s)
Merck Sharp & Dohme Corp.

§ 102 Challenge
N

§ 103 challenge
Y: Claims 1-2, 5-15

Claim Types Challenged Under § 103
Composition of Matter Formulation Method of Treatment Manufacturing Other (Vector, Host Cell)

§ 103 Challenge Instituted
Awaiting Institution Decision

Settled / Challenged Claims Disclaimed / Challenge Terminated
Y (Disclaimed in Part- Claim 4 Disclaimed Prior to Institution Decision)

IPR Status
Challenges Also Include Written Description (Claims 1-15) and Enablement (Claims 1-15). Claim 4 Disclaimed Prior to Institution Decision. Awaiting Institution Decision

approved_indications U.S. Patent Litigations

PACER

Case No(s):

2:25-cv-03179 (D.N.J.)

U.S. Patent Nos.
10,865,400 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 11,041,149 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 11,066,656 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 11,952,600 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,018,298 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,037,618 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,049,652 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,054,758 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,077,791 (Ph20 Polypeptide Variants with a Modification at Position 309 of the Ph20 Polypeptide and a Method of Making Thereof) 12,091,692 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,104,185 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,110,520 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,152,262 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,195,773 (Ph20 Polypeptide Variants, Formulations and Uses Thereof) 12,264,345 (Ph20 Polypeptide Variants, Formulations and Uses Thereof)

Plaintiffs
Halozyme, Inc.

Defendants
Merck Sharp & Dohme LLC

Status
Case Ongoing

BPCIA
N

Methodology

Information contained in the Venable BiologicsHQ database relates to FDA-approved drug products listed in the CDER Purple Book or on the FDA website (www.fda.gov). Information relating to FDA licensed products, FDA-approved indications, and aBLA and 505(b)(2) applications is obtained from public sources including the U.S. FDA website (www.fda.gov). Information relating to litigations is given only for cases active from January 31, 2010 onward. Information relating to foreign biosimilar / biologics follow-on products approved in Australia, Canada, the E.U., Japan and South Korea is from public sources. Statistics graphics are compiled from information contained in the Venable BiologicsHQ database.

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