BR112021026789A2 - Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmas - Google Patents
Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmasInfo
- Publication number
- BR112021026789A2 BR112021026789A2 BR112021026789A BR112021026789A BR112021026789A2 BR 112021026789 A2 BR112021026789 A2 BR 112021026789A2 BR 112021026789 A BR112021026789 A BR 112021026789A BR 112021026789 A BR112021026789 A BR 112021026789A BR 112021026789 A2 BR112021026789 A2 BR 112021026789A2
- Authority
- BR
- Brazil
- Prior art keywords
- sialidase
- fusion proteins
- methods
- recombinant human
- sialidase fusion
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4244—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6815—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01018—Exo-alpha-sialidase (3.2.1.18), i.e. trans-sialidase
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962870403P | 2019-07-03 | 2019-07-03 | |
| US202062957011P | 2020-01-03 | 2020-01-03 | |
| PCT/US2020/040828 WO2021003469A2 (en) | 2019-07-03 | 2020-07-03 | Recombinant human sialidases, sialidase fusion proteins, and methods of using the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112021026789A2 true BR112021026789A2 (pt) | 2022-05-10 |
Family
ID=74101301
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112021026789A BR112021026789A2 (pt) | 2019-07-03 | 2020-07-03 | Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmas |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20220356457A1 (https=) |
| EP (1) | EP3994275A4 (https=) |
| JP (2) | JP7777988B2 (https=) |
| KR (1) | KR20220032576A (https=) |
| CN (1) | CN114258431A (https=) |
| AU (1) | AU2020301037A1 (https=) |
| BR (1) | BR112021026789A2 (https=) |
| CA (1) | CA3145676A1 (https=) |
| WO (1) | WO2021003469A2 (https=) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102914621B1 (ko) | 2018-01-03 | 2026-01-21 | 팔레온 파마슈티칼스 인크. | 재조합 인간 시알리다제, 시알리다제 융합 단백질, 및 이를 사용하는 방법 |
| BR112021026852A2 (pt) * | 2019-07-03 | 2022-02-22 | Palleon Pharmaceuticals Inc | Sialidases recombinantes e métodos de uso das mesmas |
| US20220387616A1 (en) * | 2019-07-03 | 2022-12-08 | Palleon Pharmaceuticals Inc. | Sialidase-her2-antibody fusion proteins and methods of use thereof |
| JP7777988B2 (ja) * | 2019-07-03 | 2025-12-01 | パレオン ファーマシューティカルズ インコーポレイテッド | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびその使用方法 |
| WO2025217138A1 (en) * | 2024-04-09 | 2025-10-16 | Palleon Pharmaceuticals Inc. | Recombinant human sialidases, sialidase fusion proteins, and methods of using the same |
| WO2026037175A1 (zh) | 2024-08-16 | 2026-02-19 | 上海宝济药业股份有限公司 | 靶向靶细胞的复合物及其应用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE474925T1 (de) * | 1993-05-17 | 2010-08-15 | Genentech Inc | Rekombinante cho zell sialidase |
| US8512710B2 (en) * | 2002-11-22 | 2013-08-20 | Ansun Biopharma, Inc. | Class of therapeutic protein based molecules |
| WO2007108464A1 (ja) * | 2006-03-20 | 2007-09-27 | Kyowa Hakko Kogyo Co., Ltd. | 哺乳動物由来細胞質シアリダーゼに対する抗体 |
| CN100376689C (zh) * | 2006-03-28 | 2008-03-26 | 北京大学 | 一种预测达菲类药物用药安全性的方法 |
| CN101896616B (zh) * | 2007-10-12 | 2014-06-04 | 西格马-奥利奇股份有限公司 | 提高糖蛋白唾液酸化作用的组合物与方法 |
| AU2010270979B2 (en) * | 2009-06-22 | 2015-04-23 | Medimmune, Llc | Engineered Fc regions for site-specific conjugation |
| JP2013510169A (ja) * | 2009-11-06 | 2013-03-21 | ネクスバイオ,インク. | 呼吸器管の治療及び予防のための方法、化合物、及び組成物 |
| US10081801B2 (en) * | 2013-04-12 | 2018-09-25 | Danmarks Tekniske Universitet | Mutant sialidase having trans-sialidase activity for use in production of sialylated glycans |
| WO2018006066A1 (en) * | 2016-07-01 | 2018-01-04 | The Board Of Trustees Of The Leland Stanford Junior University | Inhibitory immune receptor inhibition methods and compositions |
| MX2018016393A (es) * | 2016-07-01 | 2019-08-12 | Univ Leland Stanford Junior | Conjugados para la edición de la superficie de la celula diana. |
| DK3630968T3 (da) * | 2017-05-26 | 2024-07-29 | Genovis Ab | Enzymer til glycananalyse |
| KR102914621B1 (ko) * | 2018-01-03 | 2026-01-21 | 팔레온 파마슈티칼스 인크. | 재조합 인간 시알리다제, 시알리다제 융합 단백질, 및 이를 사용하는 방법 |
| WO2020142727A1 (en) * | 2019-01-03 | 2020-07-09 | Palleon Pharmaceuticals Inc. | Methods and compositions for treating cancer with immune cells |
| JP7777988B2 (ja) * | 2019-07-03 | 2025-12-01 | パレオン ファーマシューティカルズ インコーポレイテッド | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびその使用方法 |
-
2020
- 2020-07-03 JP JP2021578065A patent/JP7777988B2/ja active Active
- 2020-07-03 US US17/624,121 patent/US20220356457A1/en active Pending
- 2020-07-03 EP EP20834151.1A patent/EP3994275A4/en active Pending
- 2020-07-03 AU AU2020301037A patent/AU2020301037A1/en active Pending
- 2020-07-03 BR BR112021026789A patent/BR112021026789A2/pt unknown
- 2020-07-03 CN CN202080058167.7A patent/CN114258431A/zh active Pending
- 2020-07-03 KR KR1020227003418A patent/KR20220032576A/ko active Pending
- 2020-07-03 WO PCT/US2020/040828 patent/WO2021003469A2/en not_active Ceased
- 2020-07-03 CA CA3145676A patent/CA3145676A1/en active Pending
-
2025
- 2025-11-18 JP JP2025197401A patent/JP2026032063A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2026032063A (ja) | 2026-02-25 |
| WO2021003469A2 (en) | 2021-01-07 |
| EP3994275A2 (en) | 2022-05-11 |
| CA3145676A1 (en) | 2021-01-07 |
| WO2021003469A3 (en) | 2021-04-08 |
| JP2022538894A (ja) | 2022-09-06 |
| KR20220032576A (ko) | 2022-03-15 |
| EP3994275A4 (en) | 2023-11-29 |
| US20220356457A1 (en) | 2022-11-10 |
| CN114258431A (zh) | 2022-03-29 |
| JP7777988B2 (ja) | 2025-12-01 |
| AU2020301037A1 (en) | 2022-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BR112021026789A2 (pt) | Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmas | |
| MX2020007024A (es) | Sialidasas humanas recombinantes, proteinas de fusion de sialidasa y metodos para usar las mismas. | |
| CL2020003096A1 (es) | Anticuerpos frente a entpd2, terapias de combinación y métodos de uso de los anticuerpos y las terapias de combinación | |
| BR112021021843A2 (pt) | Composições de proteína de fusão quimicamente projetada e métodos de uso das mesmas | |
| MX2022005252A (es) | Composiciones de escherichia coli y metodos de las mismas. | |
| BR112018068189A2 (pt) | proteínas de ligação induzíveis e métodos de uso | |
| PH12021500031A1 (en) | Anti-il2 receptor gamma antigen-binding proteins | |
| BR112015021979A2 (pt) | Anticorpos humanos para grem1 | |
| BR112018070676A2 (pt) | construtos de ligação a antígeno multiespecífico que têm como alvo agentes imunoterapêuticos | |
| BR112019000098A2 (pt) | proteína de fornecimento ao cérebro, método de tratamento e/ou profilaxia de distúrbios cerebrais em mamíferos que possuem ou encontram-se em risco de desenvolver o mencionado distúrbio e método de diagnóstico e/ou detecção de distúrbios cerebrais em mamíferos suspeitos de possuir ou que se encontram em risco de desenvolver o mencionado distúrbio | |
| BRPI0819909B8 (pt) | anticorpo sintético humano ou humanizado isolado ou um fragmento funcional do mesmo, fragmento funcional e composição farmacêutica | |
| BR112016013347A2 (pt) | anticorpo monoclonal humano neutralizante anti-il-33 | |
| BR112015017307A2 (pt) | composições de espécies com baixa acidez e métodos para produção e uso das mesmas | |
| BR112016014810A2 (pt) | Antagonistas de fcrn e métodos de uso | |
| BR112018010160A2 (pt) | inibidor da c1 esterase humana recombinante e usos do mesmo | |
| BR112022011570A2 (pt) | Anticorpos anti-mertk e métodos de uso dos mesmos | |
| BR112017021484A2 (pt) | anticorpos de direcionamento à proteína morfogenética óssea 9 (bmp9) e métodos para os mesmos | |
| BR112021025077A2 (pt) | Anticorpos anti-sortilina para uso em terapia | |
| BR112014024751A2 (pt) | antígenos de clostridium difficile | |
| BR112017017609A2 (pt) | proteína de fusão fc, e, composição farmacêutica. | |
| BR112021016791A2 (pt) | Proteínas de ligação de antígenos que se ligam a bcma | |
| BR112022008653A2 (pt) | Conjugado anticorpo-fármaco, método para tratar câncer, e, uso do conjugado anticorpo-fármaco | |
| MX2023000243A (es) | Sialidasas recombinantes con sensibilidad reducida a la proteasa, proteinas de fusion de sialidasa y metodos para utilizarlas. | |
| PH12018502275B1 (en) | Interferon beta antibodies and uses thereof | |
| BR112022007776A2 (pt) | Composições e métodos para minimizar a perda de proteína em baixas concentrações de proteína |