Atorvastatin Calcium

Recorlev now holds four Orange Book-listed patents to 2040 CHICAGO--(BUSINESS WIRE)--Aug. 25, 2025-- Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a fast-growing biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies, today announced the U.S Patent and Trademark Office has issued patent number 12,377,096 to the Company for Recorlev® (levoketoconazole) and that this patent is now listed in the publication, “Approved Drug Products with Therapeutics Equivalence Evaluations,” commonly known as the “Orange Book.” This patent, entitled “Methods of Treating Disease with Levoketoconazole,” covers therapeutic uses of levoketoconazole in methods that minimize drug-drug interactions between levoketoconazole and other commonly co-administered drugs known as MATE1 substrates, and extends to March 2040. “We are pleased to expand and further strengthen the intellectual property protection for Recorlev with the grant of our latest patent and its addition to the FDA’s Orange Book,” said John Shannon, Chief Executive Officer of Xeris. “Recorlev represents a meaningful therapeutic advancement for patients with endogenous Cushing’s syndrome and hypercortisolemia, a complex and underserved condition. As we continue to make strategic investments in education, patient support, and market access, we are equally committed to protecting the long-term value of this important asset. Strengthening our IP position reinforces our confidence in Recorlev’s growth potential and our mission to improve the lives of patients with rare endocrine diseases.” Orange Book-listed patents cover drugs that the FDA has approved and deemed both safe and effective for the general public's use. Inclusion in the book's list of patents can make it easier for drug makers to monitor for new generic drugs that could potentially arrive on the U.S. market and infringe on their patents. Recorlev® (levoketoconazole) was approved by the FDA in December 2021 for the treatment of endogenous Cushing’s syndrome in adult patients for whom surgery is not an option or has not been curative. Recorlev is an adrenal steroidogenesis inhibitor and a purified enantiomer of ketoconazole. The product is protected by multiple patents listed in the FDA’s Orange Book. Recorlev is not classified as a controlled substance by the U.S. Drug Enforcement Administration (DEA). Important Safety Information RECORLEV is contraindicated in patients: With cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT >3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug-induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes With prolonged QTcF interval >470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or long QT syndrome With hypersensitivity to levoketoconazole, ketoconazole, or any excipient in RECORLEV Taking certain drugs that are sensitive substrates of CYP3A4 or CYP3A4 and P-gp RECORLEV may lead to hypocortisolism with a potential for life-threatening adrenal insufficiency. Dosage reduction or interruption may be necessary Hypersensitivity to RECORLEV has been reported. Anaphylaxis has been reported with oral ketoconazole RECORLEV may lower serum testosterone in men and women. Inform patients to report associated symptoms Most common adverse reactions are nausea/vomiting, hypokalemia, hemorrhage/contusion, systemic hypertension, headache, hepatic injury, abnormal uterine bleeding, erythema, fatigue, abdominal pain/dyspepsia, arthritis, upper respiratory infection, myalgia, arrhythmia, back pain, insomnia/sleep disturbances, and peripheral edema Avoid use of strong CYP3A4 inhibitors and inducers 2 weeks before and during RECORLEV treatment. Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating RECORLEV. For atorvastatin, metformin, and gastric acid modulators, see full Prescribing Information for recommendations regarding concomitant use with RECORLEV Breastfeeding is not recommended during treatment and for one day after final dose With cirrhosis, acute liver disease or poorly controlled chronic liver disease, baseline AST or ALT >3 times the upper limit of normal, recurrent symptomatic cholelithiasis, a prior history of drug-induced liver injury due to ketoconazole or any azole antifungal therapy that required discontinuation of treatment, or extensive metastatic liver disease Taking drugs that cause QT prolongation associated with ventricular arrhythmias, including torsades de pointes With prolonged QTcF interval >470 msec at baseline, history of torsades de pointes, ventricular tachycardia, ventricular fibrillation, or long QT syndrome With hypersensitivity to levoketoconazole, ketoconazole, or any excipient in RECORLEV Taking certain drugs that are sensitive substrates of CYP3A4 or CYP3A4 and P-gp Please see Medication Guide and full Prescribing Information, including Boxed Warning, for RECORLEV. About Xeris Xeris (Nasdaq: XERS) is a fast-growing biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products: Recorlev®, for the treatment of endogenous Cushing’s syndrome; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, and a gastrointestinal motility inhibitor when used as a diagnostic aid; and Keveyis®, a proven therapy for primary periodic paralysis. Xeris also has a pipeline of development programs led by XP-8121, a Phase 3-ready, once-weekly subcutaneous injection for hypothyroidism, as well as early-stage programs leveraging Xeris’ technology platforms, XeriSol® and XeriJect®, for its partners. Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit www.xerispharma.com, or follow us on X, LinkedIn, or Instagram. Forward-Looking Statements Any statements in this press release other than statements of historical fact are forward-looking statements. Forward-looking statements include, but are not limited to, statements about future expectations, plans, opportunities, and prospects for Xeris Biopharma Holdings, Inc., including statements regarding its strategic investments in education, patient support, and market access, commitment to protecting the long-term value of its assets, the growth potential of its drug products, including Recorlev, the market and therapeutic potential of its products and product candidates, and other statements containing the words “will,” “would,” “continue,” “expect,” “should,” “anticipate,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on numerous assumptions and assessments made in light of Xeris’ experience and perception of historical trends, current conditions, business strategies, operating environment, future developments, geopolitical factors and other factors it believes appropriate. By their nature, forward-looking statements involve known and unknown risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. The various factors that could cause Xeris’ actual results, performance or achievements, industry results and developments to differ materially from those expressed in or implied by such forward-looking statements, include, but are not limited to, its financial position and need for financing, including to fund its product development programs or commercialization efforts, whether its products will achieve and maintain market acceptance in a competitive business environment, its reliance on third-party suppliers, including single-source suppliers, its reliance on third parties to conduct clinical trials, the ability of its product candidates to compete successfully with existing and new drugs, and its collaborators’ ability to protect its intellectual property and proprietary technology, and general macroeconomic and geopolitical conditions, including the possibility of an economic downturn, changes in governmental priorities and resources, announced or implemented tariffs, and market volatility. No assurance can be given that such expectations will be realized and persons reading this communication are, therefore, cautioned not to place undue reliance on these forward-looking statements. Additional risks and information about potential impacts of financial, operational, economic, competitive, regulatory, governmental, technological, and other factors that may affect Xeris can be found in Xeris’ filings, including its most recently filed Annual Report on Form 10-K and subsequent filings with the U.S. Securities and Exchange Commission, the contents of which are not incorporated by reference into, nor do they form part of, this communication. Forward-looking statements in this communication are based on information available to management, as of the date of this communication and, while the Company believes its assumptions are reasonable, actual results may differ materially. Subject to any obligations under applicable law, the Company does not undertake any obligation to update any forward-looking statement whether as a result of new information, future developments or otherwise, or to conform any forward-looking statement to actual results, future events, or to changes in expectations. View source version on businesswire.com: https://www.businesswire.com/news/home/20250825676155/en/ Xeris Investor Contact Allison Wey Senior Vice President, Investor Relations and Corporate Communications awey@xerispharma.com Source: Xeris Biopharma Holdings, Inc.

立项一个仿制药，最先被问到的往往不是“能不能做出来”，而是“能不能做得出来又不踩雷”，这里的“雷”99%是专利。 一、原研药的“知识产权护城河”到底有多深？ 原研公司绝不会只申请一件专利，而是把能想到的保护点全部锁死。 1.基础化合物专利：这是最核心的壁垒，保护药物活性成分（API）的化学结构本身。这是仿制药绕不开的“硬骨头”，通常也是原研药独占期的基石。 2.晶型专利：同一化合物可能形成不同的晶体结构（多晶型）。某些晶型可能在稳定性、溶解性、生物利用度上更优，原研公司会为这些优势晶型申请专利。例如：诺华的格列卫（甲磺酸伊马替尼）的β晶型专利（涉及CN97197460.X等）就是著名的案例，在中国曾引发诉讼。 3.制剂专利：保护药物的特定剂型、处方组成（辅料种类和比例）、制备工艺等，旨在延长对特定给药形式的保护。 4.用途专利（适应症专利）：保护药物的新医疗用途或新适应症。即使化合物专利过期，针对新发现的适应症治疗用途仍可能受到保护。例如：西地那非（万艾可）最初用于心绞痛，后发现用于ED，其ED用途专利（US09261260等）提供了额外保护。 5.制备方法专利：保护合成API或制造制剂的特定、优化的工艺路线，仿制药企业需要开发不侵权的替代工艺。 6.组合物专利：保护药物与其他活性成分的特定组合。 这些专利到期日参差错落，仿制药立项的第一件事就是画出“专利时间轴”：谁最先到期、谁最难撼动、谁是纸老虎，一目了然。 二、仿制药立项的专利“扫雷” 1.锁定目标专利 官方登记与清单： 中国：NMPA的《中国上市药品专利信息登记平台》是法定登记平台。查询目标原研药登记的所有相关专利（化合物、用途、制剂等）。 美国：FDA的“橙皮书”列出了新药获批时提交的、与其相关的专利及其到期日。 其他主要市场：查询相应监管机构，如EMA、PMDA、HealthCanada类似数据库或药品信息。 检索策略：以原研公司、药物通用名、化学名、CAS号、关键适应症为核心，结合IPC/CPC分类号进行组合检索。 地域覆盖：需覆盖目标仿制药上市的所有国家和地区（中国、美国、欧洲、日本、印度等）。 类型覆盖：不仅关注已授权专利，更要密切关注处于审查阶段的专利申请（公开文本），它们可能在未来构成威胁。 2.深度专利分析（FTO初步评估）： 权利要求解读：这是核心中的核心。逐字逐句分析独立权利要求和从属权利要求保护的范围边界。明确哪些技术特征被保护，仿制行为可能落入哪些权利要求的范围。需要专业专利律师或专利分析师的深度参与。 专利家族与法律状态：理清目标专利在全球的同族专利情况，确认其在目标市场（尤其是中国）的当前法律状态（有效、失效、届满、被异议/无效中）。 到期日计算：精确计算关键专利（特别是化合物专利、关键制剂/用途专利）在目标市场的到期日（考虑专利期补偿/延长，如中国的专利权期限补偿制度，美国的PTE，欧洲的SPC）。这是仿制药上市的理论最早时间点。 稳定性评估（无效可能性）：初步评估核心专利的稳定性。查找是否存在可能使其无效的现有技术（在先专利、科技文献、公开使用证据等）？专利撰写是否存在瑕疵，如公开不充分、不支持、修改超范围等？这直接关系到后续是否发起专利挑战。 三、主动进攻：专利挑战的三板斧 等专利自然到期是最笨的办法。只要有一丝缝隙，就要主动出击。 1.专利无效宣告 这是最硬的正面战场。石药打达沙替尼晶型专利（第48328号无效决定），前后提交12篇对比文件，最终把原研晶型专利一锅端。证据必须铁证如山，论证必须“刀刀见骨”。 2.不侵权设计（DesignAround） 换晶型：阿托伐他汀钙我们选了与原研专利完全不同的晶型，溶出曲线却做到Q1/Q2等效。 改工艺：原研用流化床包衣，我们改挤出滚圆；原研用HPMC，我们换PEO，每一步都让专利律师签字确认“不踩线”。 适应症切割：如果原研有ED用途专利，标签上直接删掉相关表述，临床方案也同步收窄。 规避设计最怕“顾头不顾腚”，改完晶型又掉进制剂专利的坑。因此每出一个新方案，立即补一轮FTO。 3.Bolar例外：合法抢跑 中国《专利法》第75条第五项就是护身符。我们在化合物专利到期前18个月启动BE试验，样品生产、稳定性研究全部合法。但红线必须牢记：样品只能用于注册，仓库钥匙由QA和法律部双签。 四、诉讼来了，怎么办？ 一旦发起专利挑战（尤其是提交第IV类声明或进行规避设计），或原研药企主动发起维权，诉讼风险陡增。有效应对是关键： 1.积极应诉，绝不回避： 收到诉状后，迅速组建专业应诉团队（内部法务、外部资深知识产权诉讼律师、技术专家）。 在法定时限内（通常15日答辩期）提交答辩状，进行有力抗辩。 2.核心抗辩策略： 不侵权抗辩：详细论证仿制药产品或方法的技术方案未落入涉案专利权利要求的保护范围，进行细致的特征比对分析。 专利无效抗辩：在侵权诉讼中，通常可同时向CNIPA提起专利无效宣告请求，法院可能（视情况）中止侵权诉讼，等待无效决定，成功无效专利则釜底抽薪。 现有技术/先用权抗辩：如能证明在专利申请日前已掌握相同技术并做好制造准备（需严格证据）。 Bolar例外抗辩：证明被诉行为属于为行政审批目的。 3.诉讼策略运用： 管辖权异议：在符合条件下提出，争取有利诉讼地点。 证据开示与质证：充分利用程序获取对方证据，并对对方证据进行有效质证。 专家证人：聘请技术专家就专利技术、侵权比对等出具专家意见，辅助法官理解复杂技术问题。 和解谈判：诉讼成本高昂且结果不确定。在适当时机，基于对案件走向的评估，可与对方进行许可谈判或达成其他和解方案，如延迟上市协议-需注意反垄断审查风险。 真实案例启示：诺华诉正大天晴等甲磺酸伊马替尼专利侵权系列案，该案涉及化合物专利到期后的晶型专利。正大天晴等被告积极应诉，一方面进行不侵权抗辩（主张其产品使用的晶型不同），另一方面向CNIPA请求宣告诺华的晶型专利无效；诉讼过程漫长且激烈，最终部分案件达成和解，部分案件法院基于无效决定作出判决。没有永远的敌人，只有永远的利益。 五、我们踩过的雷 1.漏检外围专利 化合物专利到期就上马，结果原研还有晶型+制剂双保险，产品上市3个月被下禁令。 教训：外围专利必须单独出一份FTO报告，由合伙人级别的律师签字。 2.权利要求解读失误 把“约5%”理解成“±2%”，结果法院认定“约”就是“±0.5%”，直接侵权。 教训：所有数字范围、功能限定都要让制剂和专利律师一起抠字眼。 3.规避设计“换汤不换药” 换晶型时忘了热力学稳定性，BE试验溶出突变，被迫重新开发。 教训：技术可行性永远排在法律可行性之后。 4.Bolar例外越界 临床样品多生产了一批，被原研抓到“商业规模”证据。 教训：QA留样、生产批记录、发运单据，所有数据链必须闭环。 仿制药的“仿”，绝非简单的复制粘贴。在知识产权保护日益严密、法规环境不断完善的今天，专利问题已成为仿制药立项、研发、注册、上市全生命周期管理的核心主线。唯有以专业为矛，以策略为盾，方能在这场“仿创结合”中赢得未来。 参考来源： [1]《药品专利纠纷早期解决机制实施办法（试行）》 [2]《药品专利纠纷早期解决机制的实施进展与展望》 [3]Pharmaceuticals: Commission Refines Intellectual Property Rules. [4]《遭7家仿制药企进攻，原研药“躲”过集采》 [5]Federal Court of Appeal Raises New Questions on Obviousness-Type Double Patenting. [6]《奥希替尼首仿获批，留给仿制企业不少思考》 立即扫码加入药事纵横交流群