WO2020197230A1 - 인간 히알루로니다제 ph20의 변이체와 약물을 포함하는 피하투여용 약학 조성물 - Google Patents
인간 히알루로니다제 ph20의 변이체와 약물을 포함하는 피하투여용 약학 조성물 Download PDFInfo
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Abstract
Description
Claims (33)
- (a) 약물 및(b) PH20 변이체를 포함하고,상기 PH20 변이체는 서열번호 1의 서열을 갖는 야생형 PH20에 있어, S343E, M345T, K349E, L353A, L354I, N356E 및 I361T로 구성된 군에서 선택된 하나 이상의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 상기 PH20 변이체는 L354I 및 N356E로 구성된 군에서 선택된 하나 이상의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 상기 PH20 변이체는 서열번호 1의 야생형 PH20의 알파나선 부위 및 그 연결부위에 해당하는 부위로 구성된 군에서 선택된 하나 이상의 부위에서 하나 이상의 아미노산 잔기의 치환을 더 포함하는 것을 특징으로 하는 약학 조성물.
- 제3항에 있어서, 상기 서열번호 1의 야생형 PH20의 알파나선 부위는 알파나선 8 부위(S347~C381)이고, 그 연결부위는 알파나선 7과 알파나선 8 연결 부위(A333~R346)인 것을 특징으로 하는 약학 조성물.
- 제4항에 있어서, 상기 서열번호 1의 야생형 PH20의 알파나선 부위 및 그 연결부위에 해당하는 부위는 T341~N363, T341~I361, L342~I361, S343~I361, I344~I361, M345~I361 또는 M345~N363인 것을 특징으로 약학 조성물.
- 제4항에 있어서, 상기 서열번호 1의 야생형 PH20의 알파나선 8 부위(S347~C381) 및 알파나선 7과 알파나선 8 연결 부위(A333~R346)로 구성된 군에서 선택된 하나 이상의 부위가 Hyal1의 대응되는 부위의 아미노산 서열의 일부 아미노산 잔기로 치환된 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 상기 PH20 변이체는 L354I 및/또는 N356E의 아미노산 잔기의 치환을 포함하고,추가적으로 T341, L342, S343, I344, M345, S347, M348, K349, L352, L353, D355, E359, I361 및 N363로 구성된 군에서 선택된 하나 이상의 위치에서의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제7항에 있어서, 상기 PH20 변이체는 L354I 및/또는 N356E의 아미노산 잔기 치환을 포함하고,추가적으로 T341S, L342W, S343E, I344N, M345T, S347T, M348K, K349E, L352Q, L353A, D355K, E359D, I361T 및 N363G로 구성된 군에서 선택된 하나 이상의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제7항에 있어서, 상기 PH20 변이체는 M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제9항에 있어서, 상기 PH20 변이체는 추가적으로 T341S, L342W, S343E, I344N 및 N363G로 구성된 군에서 선택된 하나 이상의 아미노산 잔기의 치환을 포함하는 것을 특징으로 하는 약학 조성물.
- 제10항에 있어서, 상기 PH20 변이체는 다음으로 구성된 군에서 선택된 어느 하나의 아미노산 치환을 포함하는 것을 특징으로 하는 약학 조성물:(a) T341S, L342W, S343E, I344N, M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T;(b) L342W, S343E, I344N, M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T;(c) M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T;(d) M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D, I361T, 및 N363G(e) I344N, M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T; 및(f) S343E, I344N, M345T, S347T, M348K, K349E, L352Q, L353A, L354I, D355K, N356E, E359D 및 I361T
- 제1항 내지 제11항 중 어느 한 항에 있어서,상기 PH20 변이체는 추가적으로 C-말단 및 N-말단 중 하나 이상의 말단에서 일부 아미노산 잔기가 결실된 것을 특징으로 약학 조성물.
- 제12항에 있어서, 상기 PH20 변이체는 N-말단의 M1 내지 P42로 구성된 군에서 선택된 아미노산 잔기 앞에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 약학 조성물.
- 제13항에 있어서, 상기 PH20 변이체는 N-말단의 L36, N37, F38, R39, A40, P41 또는 P42 잔기 앞에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 약학 조성물.
- 제12항에 있어서, 상기 PH20 변이체는 C-말단의 V455 내지 L509로 구성된 군에서 선택된 아미노산 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 약학 조성물.
- 제15항에 있어서, 상기 PH20 변이체는 C-말단의 V455 내지 S490로 구성된 군에서 선택된 아미노산 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 약학 조성물.
- 제16항에 있어서, 상기 PH20 변이체는 C-말단의 V455, C458, D461, C464, I465, D466, A467, F468, K470, P471, P472, M473, E474, T475, E476, P478, I480, Y482, A484, P486, T488 또는 S490 잔기 다음에서 절단되어 일부 아미노산 잔기가 결실된 것을 특징으로 하는 약학 조성물.
- 제1항 내지 제17항 중 어느 한 항에 있어서, 상기 PH20 변이체는 N-말단에 추가로 인간 Hyaluronidase-1(Hyal1), 인간 성장호르몬 또는 인간 혈청 알부민 유래의 신호 펩티드를 포함하는 것을 특징으로 하는 약학 조성물.
- 제1항 내지 제11항 중 어느 한 항에 있어서, 상기 PH20 변이체는 서열번호 5 내지 서열번호 50의 아미노산 서열로 구성된 군에서 선택되는 것을 특징으로 하는 약학 조성물.
- 제19항에 있어서, 상기 PH20 변이체는 서열번호 44의 서열을 갖는 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 상기 약물은 단백질 의약품(protein drugs), 항체(antibody), 소분자 화합물(small molecules), 앱타머(aptamer), RNAi, antisense 또는 세포 치료제인 것을 특징으로 하는 약학 조성물.
- 제21항에 있어서, 상기 약물은 항체, 수용성 수용체 또는 수용성 수용체와 Fc 융합 단백질인 것을 특징으로 하는 약학 조성물.
- 제22항에 있어서, 상기 항체는 4-1BB, 인테그린 (integrin), 아밀로이드 베타 (amyloid beta), 안지오포에틴, 안지오포에틴 유사물질3, B세포활성인자 (B-cell activating factor, BAFF), B7-H3, 보체5 (complement 5), CCR4, CD3, CD4, CD6, CD11a, CD19, CD20, CD22, CD30, CD33, CD38, CD52, CD62, CD79b, CD80, CGRP, 클라우딘18 (Claudin-18), 보체요소 D (complement factor D), CTLA4, DLL3, EGF 수용체, 혈우병인자, Fc 수용체, FGF23, 폴레이트 (folate) 수용체, GD2, GM-CSF, HER2, HER3, 인터페론 수용체, 인터페론 감마, IgE, IGF-1 수용체, 인터루킨1, 인터루킨2 수용체, 인터루킨4 수용체, 인터루킨5, 인터루킨5 수용체, 인터루킨6, 인터루킨6 수용체, 인터루킨7, 인터루킨12/23, 인터루킨13, 인터루킨17A, 인터루킨17 수용체A, 인터루킨31 수용체, 인터루킨36 수용체, LAG3, LFA3, NGF, PVSK9, PD-1, PD-L1, RANK-L, SLAMF7, 조직인자 (Tissue factor), TNF, VEGF 및 vWF로 구성된 군에서 선택된 하나 이상의 항원과 결합하는 것을 특징으로 하는 약학 조성물.
- 제22항에 있어서, 상기 항체는 유토밀루맙 (Utomilumab), 나탈리주맙 (Natalizumab), 에트롤리주맙 (Etrolizumab), 베돌리주맙 (Vedolizumab), 비마그루맙 (Bimagrumab), 바피네우주맙 (Bapineuzumab), 크레네주맙(Crenezumab), 솔라네주맙 (Solanezumab), 아두카누맙 (Aducanumab), 간테네루맙 (Gantenerumab), AMG 780, MEDI 3617, 네스바쿠맙 (Nesvacumab), 바누씨주맙 (Vanucizumab), 에비나쿠맙 (Evinacumab), 타발루맙(Tabalumab), 라나루맙 (Lanalumab), 베리무맙 (Belimumab), 옴부르타맙 (omburtamab), 라불리주맙 (Ravulizumab), 에쿨리주맙 (Eculizumab), 모가물리주맙 (Mogamulizumab), 오텔릭시주맙 (Otelixizumab), 테플리주맙 (Teplizumab), 무로모납 (Muromonab), 테벤타프스프 (Tebentafusp), 블리나두모맙 (Blinatumoma), REGN1979, 이발리주맙 (Ibalizumab), 자놀리무맙 (Zanolimumab), 이톨리주맙 (Itolizumab), 에팔리주맙 (Efalizumab), 이네빌리주맙 (Inebilizumab), 타파시타맙 (Tafasitamab), 론카스툭시맙 테시린 (Loncastuximab tesirine), 오크렐리주맙 (Ocrelizumab), 우블리툭시맙 (Ublituximab), 오비누투주맙 (Obinutuzumab), 오파투무맙 (Ofatumumab), 리툭시맙 (Rituximab), 토시투모맙 (Tositumomab), 이브리투모맙 티욱세탄 (Ibritumomab tiuxetan), 에프라투주맙 (Epratuzumab), 이노투주맙 오조가마이신 (Inotuzumab ozogamicin), 목세투모맙 파수도톡스 (Moxetumomab pasudotox), 브렌툭시맙 베도틴 (Brentuximab vedotin), 바다스툭시맙 탈리닌 (Vadastuximab talirine), 젬투주맙 오조가마이신 (Gemtuzumab ozogamicin), 다라투무맙 (Daratumumab), 이사툭시맙 (Isatuximab), 알렘투주맙 (Alemtuxumab), 크리잔리주맙 (Crizanlizumab), 폴라투주맙 베도틴 (Polatuzumab vedotin), 갈릭시맙 (Galiximab), 엪티네주맙 (Eptinezumab), 프레마네주맙 (Fremanezumab), 갈카네주맙 (Galcanezumab), 에레누맙 (Erenumab), 졸베툭시맙 (Zolbetuximab), 람팔리주맙 (Lampalizumab), 트레멜리무맙 (Tremelimumab), 잘리프렐리맙 (Zalifrelimab), 이플리무맙 (Ipilimumab), 로발피투주맙 테시린 (Rovalpituzumab tesirine), 세툭시맙 (Cetuximab), 데파툭시주맙 (Depatuxizumab), 잘루투무맙 (Zalutumumab), 네시투무맙 (Necitumumab), 파니투무맙 (Panitumumab), 에미시주맙 (Emicizumab), 니포칼리맙 (Nipocalimab), 로잔놀릭시주맙 (Rozanolixizumab), 부로스맙 (Burosumab), 팔레투주맙 (Farletuzumab), 미르베툭시맙 소랍탄신 (Mirvetuximab soravtansine), 디누툭시맙 (Dinutuximab), 낙시타맙 (Naxitamab), 오틸리맙 (Otilimab), 마르게툭시맙 (Margetuximab), 페르투주맙 (Pertuzumab), 트라스투주맙 (Trastuzumab), 트라수투주맙 데룩테칸 (Trastuzumab deruxtecan), 트라수투주맙 엠탄신 (Trastuzumab emtansine), 트라수투주맙 두오카르마진 (Trastuzumab duocarmazine), 파트리투맙 (Patritumab), 아니프롤루맙 (Anifrolumab), 에마팔루맙 (Emapalumab), 리겔리주맙 (Ligelizumab), 오말리주맙 (Omalizumab), 달로투주맙 (Dalotuzumab), 피기투무맙 (Figitumumab), 테프로투무맙 (Teprotumumab), 게보키주맙 (Gebokizumab), 카나키누맙(Canakinumab), 다클리주맙 (Daclizumab), 바실릭시맙(Basiliximab), 두필루맙 (Dupilumab), 메폴리주맙 (Mepolizumab), 레슬리주맙 (Reslizumab), 벤랄리주맙 (Benralizumab), 클라자키주맙 (Clazakizumab), 올로키주맙 (Olokizumab), 시루쿠맙 (Sirukumab), 실툭시맙 (Siltuximab), 사릴루맙 (Sarilumab), 사트랄리주맙 (Satralizumab), 토실리주맙 (Tocilizumab), REGN88, 세쿠키누맙 (Secukinumab), 우스테키누맙 (Ustekinumab), 브리아키누맙 (Briakinumab), 레브리키주맙 (Lebrikizumab), 트랄로키누맙 (Tralokinumab), 익세키주맙 (Ixekizumab), 비메키주맙 (Bimekizumab), 브로달루맙 (Brodalumab), 브라지쿠맙 (Brazikumab), 구셀쿠맙 (Guselkumab), 리산키주맙 (Risankizumab), 틸드라키주맙 (Tildrakizumab), 미리키주맙 (Mirikizumab), 네몰리주맙 (Nemolizumab), 스페솔리맙 (Spesolimab), 렐라틀리맙 (Relatlimab), 나르소플리맙 (Narsoplimab), 파시누맙 (Fasinumab), 타네주맙 (Tanezumab), 알리로쿠맙 (Alirocumab), 에볼로쿠맙 (Evolocumab), 보코시주맙 (Bococizumab), 람브롤리주맙 (Lambrolizumab), 발스틸리맙 (Balstilimab), 캄렐리주맙 (Camrelizumab), 쎄미플리맙 (Cemiplimab), 도스탈리맙 (Dostarlimab), 프롤골리맙 (Prolgolimab ), 신틸리맙 (Sintilimab), 스파르탈리주맙 (Spartalizumab), 티슬레리주맙 (Tislelizumab), 펨브롤리주맙 (Pembrolizumab), 니볼루맙 (Nivolumab), 아테졸리주맙 (Atezolizumab), 아벨루맙 (Avelumab), 엔바폴리맙 (Envafolimab), 둘발루맙 (Durvalumab), 빈트라푸스프 알파 (Bintrafusp alpha), 데노수맙 (Denosumab), 엘로투주맙 (Elotuzumab), 콘시주맙 (Concizumab), 말스타시맙 (Marstacimab), 인플릭시맙 (Infliximab), 아달리무맙 (Adalimumab), 골리무맙 (Golimumab), 세르톨리주맙 페골 (Certolizumab pegol), 오조랄리주맙 (Ozoralizumab), 브롤루시주맙 (Brolucizumab), 라니비주맙 (Ranibizumab), 베바시주맙 (Bevacizumab), 파리시맙 (Faricimab), 라무시루맙 (Ramucirumab) 및 카플라시주맙 (Caplacizumab)으로 구성된 군에서 선택된 1종 이상인 것을 특징으로 하는 약학 조성물.
- 제22항에 있어서, 상기 수용성 수용체 또는 수용성 수용체와 Fc 융합 단백질에 포함되는 수용성 수용체는 TNF-α 수용성 수용체, VEGF 수용성 수용체, CTLA-4, 인터루킨1 수용성 수용체 및 LFA3 수용성 수용체로 구성된 군에서 선택되는 것을 특징으로 하는 약학 조성물.
- 제25항에 있어서, 상기 수용성 수용체와 Fc의 융합 단백질은 에타너셉트(Etanercept), 아플리버셉트(Aflibercept), 아바타셉트 (Abatacept), 벨라다셉트(Belatacept), 릴로나셉트 (Rilonacept) 및 알레파셉트 (Alefacept)로 구성된 군에서 선택되는 것을 특징으로 하는 약학 조성물.
- 제1항에 있어서, 완충제, 안정화제 및 계면활성제로 구성된 군에서 선택되는 하나 이상을 추가로 포함하는 것을 특징으로 하는 약학 조성물.
- 제27항에 있어서, 상기 완충제는 말산염 (malate), 폼산염 (formate), 시트르산염 (citrate), 아세테이트 (acetate), 프로피오네이트 (propionate), 피리딘 (pyridine), 피페라진 (piperazine), 카코딜산 (cacodylate), 석신산 (succinate), 2-(N-모르폴리노)에탄설폰산 (2-(N-morpholino)ethanesulfonic acid, MES), 히스티딘 (histidine), 트리스 (Tris), 비스-트리스 (bis-Tris), 인산염 (phosphate), 에탄올아민 (ethanolamine), 탄산염 (carbonate), 2-에테인술폰산 (piperazine-N,N′-bis(2-ethanesulfonic acid), PIPES), 이미다졸 (imidazole), 비스-트리스 프로판 (BIS-TRIS propane), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), MOPS (3-(N-morpholino) propanesulfonic acid), HEPES (Hydroxyethyl piperazine Ethane Sulfonic acid), 피로인산염(pyrophosphate), 및 트리에탄올아민 (triethanolamine)으로 구성된 군에서 선택된 1종 이상의 완충제이고;상기 안정화제는 탄수화물, 당류 또는 이들의 수화물, 당알콜류 또는 이들의 수화물 및 아미노산으로 구성된 군에서 선택된 1종 이상이며;상기 계면활성제는 폴리옥시에틸렌-소르비탄 지방산, 폴리에틸렌-폴리프로필렌 글리콜, 폴리옥시에틸렌-스테아레이트, 폴리옥시에틸렌 알킬 에테르, 폴리옥시에틸렌-폴리옥시프로필렌 공중합체 및 나트륨 도데실 설페이트(SDS)로 구성된 군에서 선택된 하나 이상의 비이온성 계면활성제인 것을 특징으로 하는 약학 조성물.
- 제28항에 있어서, 상기 탄수화물, 당류 또는 당알콜류는 트레할로스 또는 그의 수화물, 수크로스, 사카린, 글리세롤, 에리스톨, 트레이톨, 자일리톨, 아라비톨, 리비톨, 만니톨, 소르비톨, 갈락티톨, 푸시톨, 아이디톨, 이노시톨, 볼레미톨, 이소말트, 말티톨, 폴리글리시톨, 사이클로덱스트린(cyclodextrin), 하이드로옥실프로필 사이클로덱스트린(Hydroxypropyl Beta-cyclodextrin)및 글루코스로 구성된 군에서 선택된 1종 이상이고,상기 아미노산은 글루타민, 글루탐산, 글라이신, 라이신, 라이실라이신, 류신, 메치오닌, 발린, 세린, 셀레노메치오닌, 시트룰린, 아르지닌, 아스파라진, 아스파트산, 오르니틴, 아이소류신, 타우린, 테아닌, 트레오닌, 트립토판, 타이로신, 페닐알라닌, 프롤린, 피롤라이신, 히스티딘 및 알라닌으로 구성된 군에서 선택된 1종 이상인 것을 특징으로 하는 약학 조성물.
- 제27항에 있어서, pH 5.5 ± 2.0의 히스티딘 완충액, 트레할로스 및 메티오닌을 포함하는 것을 특징으로 하는 약학 조성물.
- 제27항에 있어서, pH 5.5 ± 2.0의 히스티딘 완충액, 트레할로스, 메티오닌 및 폴리소르베이트를 포함하는 것을 특징으로 하는 약학 조성물.
- 제31항에 있어서, pH 5.5 ± 2.0의 히스티딘 완충액, 10 내지 400 mM의 α,α-트레할로스, 1 내지 50 mM의 메티오닌 및 0.0000001% 내지 0.5%(w/v)의 폴리소르베이트를 포함하는 것을 특징으로 하는 약학 조성물.
- 제1항 내지 제32항 중 어느 한 항에 따른 약학 조성물을 포함하는 피하 투여용 주사 제형.
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CN202310758097.1A CN117100867A (zh) | 2019-03-25 | 2020-03-24 | 用于皮下注射的包含人透明质酸酶ph20变体和药物的药物组合物 |
KR1020227016935A KR102507853B1 (ko) | 2019-03-25 | 2020-03-24 | 인간 히알루로니다제 ph20의 변이체와 약물을 포함하는 피하투여용 약학 조성물 |
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DO2021000197A DOP2021000197A (es) | 2019-03-25 | 2021-09-22 | Composición farmacéutica, que comprende la variante de hialuronidasa ph20 humana y fármaco, para inyección subcutánea |
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ZA2021/08027A ZA202108027B (en) | 2019-03-25 | 2021-10-20 | Pharmaceutical composition for subcutaneous injection comprising human hyaluronidase ph20 variant and drug |
JP2022068166A JP7166478B2 (ja) | 2019-03-25 | 2022-04-18 | ヒトヒアルロニダーゼph20の変異体及び薬物を含む皮下投与用医薬組成物 |
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EP3992285A4 (en) * | 2020-01-23 | 2023-01-25 | Alteogen, Inc. | NOVEL HYALURONIC HYDROLYZING ENZYME VARIANT WITH IMPROVED STABILITY AND PHARMACEUTICAL COMPOSITION CONTAINING IT |
WO2022146947A1 (en) | 2020-12-28 | 2022-07-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
WO2022146948A1 (en) | 2020-12-28 | 2022-07-07 | Bristol-Myers Squibb Company | Subcutaneous administration of pd1/pd-l1 antibodies |
WO2023012515A2 (en) | 2021-08-02 | 2023-02-09 | argenx BV | Subcutaneous unit dosage forms |
WO2023042096A1 (en) | 2021-09-14 | 2023-03-23 | Takeda Pharmaceutical Company Limited | Facilitated delivery of concentrated antibody formulations using hyaluronidase |
WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
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