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The General Court has confirmed that a sign reproduced in a small size and in arguably a concealed location on the packaging of the product is unlikely to be noticed by the relevant consumer and, as a result, does not prove use of the mark.

T-668/19, Ardagh Metal Beverage Holdings GmbH & Co KG v EUIPO, EU:T:2021:420 (not available in English), 7 July 2021 The General Court clarifies its approach to sound marks and Article 7(1)(b) of the EU Trade Mark Regulation 2017/1001 (EUTMR).

General Court, T-193/18, Andreas Stihl v EUIPO, EU:T:2021:163, 24 March 2021 In its first judgment since the decision of the Court of Justice of the European Union (‘CJEU’) in the Red Bull case (C-124/18 P), the General Court has clarified its approach to colour marks and Article 4 of the EU Trade Mark Regulation 2017/1001 (‘EUTMR’).

Court of Justice of the European Union, MINERAL MAGIC/MAGIC MINERALS BY JEROME ALEXANDER et al, C-809/18 P, EU: C:2020:902, 11/11/2020 The Court of Justice provides clear guidance on the test to be applied under Article 8(3) of the EU Trade Mark Regulation 2017/1001 (‘EUTMR).

General Court of the European Union, Case T-573/18 FORM EINES SCHNÜRSENKELS (3D), EU:T:2020:32, 5 February 2020

Court of Justice of the European Union, EUIPO v Wajos GmbH, C-783/18 P, EU:C:2019:1073, 12 December 2019 By a judgment rendered on 12 December 2019, the Court of Justice of the European Union dismissed the appeal filed by the European Union Intellectual Property Office (EUIPO) against a judgment of the General Court allowing the registration of a bottle taking the shape of an amphora.

Background Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. Methods In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. Results eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6 ± 9.1 mL/min/1.73 m2 (P

Case T-569/18, Kordes' Rose Monique, General Court of the European Union, decision of 18 June 2019, EU:T:2019:421

Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.

The endothelin-converting enzyme (ECE)-1 gene is a candidate for human blood pressure (BP) regulation and we report the identification of the new gene variants T-839G, C-338A, L75F, A677V and C+295T. Transient transfection of the reporter constructs containing the -338A allele showed an increase in promoter activity compared with the wild-type promoter. EMSA revealed the specific binding of E2F-2 to both ECE-1b promoter sequences, with the -338A allele being associated with an increased affinity to E2F-2 compared with -338C. The clinical relevance of this finding was analyzed in 704 hypertensive patients. In untreated hypertensive women, both the -338A and -839G alleles were significantly associated with ambulatory BP values. This study provides the first evidence of a link between the cell-cycle-associated E2F family and BP regulation via a component of the endothelin system.

Aims The endothelin system plays a role in the complex pathophysiology of idiopathic dilated cardiomyopathy. We investigated whether genetic polymorphisms of the endothelin system might be associated with dilated cardiomyopathy-related cardiac phenotypes and differences in disease outcome. Methods One hundred and twenty-five unrelated dilated cardiomyopathy patients of a well characterized dilated cardiomyopathy cohort were genotyped for six common polymorphisms of the endothelin-1, endothelin-A (ETA) and endothelin-B (ETB) receptor genes using hybridization with allele-specific oligonucleotides. Results The H323H (C/T) polymorphism in exon 6 of the ETAreceptor gene was significantly associated with a shorter survival time after diagnosis. The odds ratio for carriers of the less frequent ETAT allele to die within 2 years after diagnosis was 5·5 (95% confidence interval, 1·4 to 21·0, P =0·013) compared to non-carriers. Kaplan–Meier analysis revealed a significantly different survival time for T allele carriers as compared to non-carriers as tested by logrank ( P =0·0196), Breslow ( P =0·0195), and Tarone tests ( P =0·020). The influence of the ETAH323H polymorphism on survival remained significant when known predictors of prognosis such as left ventricular ejection fraction, left ventricular end-diastolic diameter, age and NYHA functional classification were entered in a Cox proportional hazards analysis. In this model, end-diastolic diameter showed a trend to influence survival ( P =0·07) but only the ETAH323H polymorphism ( P =0·0029) was a significant independent predictor of survival. Conclusions Our results suggest that genetic variation in the ETAreceptor predicts survival in dilated cardiomyopathy patients, which might have important consequences for the identification of high-risk individuals.