RS60499B1 - Modifikovani polipeptidi za bispecifične skelete antitela - Google Patents

Modifikovani polipeptidi za bispecifične skelete antitela

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RS60499B1
RS60499B1 RS20200782A RSP20200782A RS60499B1 RS 60499 B1 RS60499 B1 RS 60499B1 RS 20200782 A RS20200782 A RS 20200782A RS P20200782 A RSP20200782 A RS P20200782A RS 60499 B1 RS60499 B1 RS 60499B1
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Partha S Chowdhury
Vaheh Oganesyan
Yariv Mazor
Nazzareno Dimasi
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Medimmune Llc
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46Hybrid immunoglobulins
    • C07K16/468Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244Interleukins [IL]
    • C07K16/248IL-6
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52Constant or Fc region; Isotype
    • C07K2317/526CH3 domain
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732Antibody-dependent cellular cytotoxicity [ADCC]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/90Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94Stability, e.g. half-life, pH, temperature or enzyme-resistance

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  • Organic Chemistry (AREA)
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  • Genetics & Genomics (AREA)
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  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
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Description

NOSEĆI BLOK ZA ZIDANJE
Oblast tehnike
Predmet pronalaska pripada, uopštcno poamatrano, u oblast gradjevinarstva odnosno u oblast visokogradnje, bliže-u oblast opštih gradjevinskih konstrukcija, zidova i gradjevinskih elemenata a konkretno u oblast pregradnih zidova za gradjevine odnosno elemenata u obliku blokova. ?'
Prema Medjuna'fodnoj klasifikaciji patenata (MKP) predmet pronalaska je označen i klasifikovan osnovnim kiasifikacionim simbolima: E 04 C 1/39 koji sc odnosi na elemente u obliku blokova karakterističnih po posebnoj prilagodjenosti i E 04 B 2/14 koji se odnosi na zidove izvedene od elemenata naslaganih jedan preko drugog kod kojih su zidovi sa šupljinama unutar elemenata.
Tehnički problem
Tehnički problem koji se želi resiti predmetnim pronalaskom sastoji se u sledećem: kako konstrukcijski izvesti element u obliku bloka za zidanje zidova gradjevina koji bi bio jednostavan za izradu, karakterističan po posebnoj prilagodjenosti koja bi olakšala sprovodjenje elektro i drugih instalacija, koji bi bio sa visokim koeficijentom termoizolacije, imao optimalna zvučna izolaciona svojstva, koji bi u zidnoj konstrukciji povećavao stabilnost i statiku gradjevine, čime bi se dobio blok za zidanje kod koga bi se smanjila upotreba maltera-vezivnog sredstva, koji bi bio praktičan i lak za zidanje i rukovanje, dugog veka trajanja, ekonomski isplatljiv i zadovoljavao standarde gradjevinskih elemenata.
Stanje tehnike
Postoje brojna rešenja gradjevinskih elemenata u obliku blokova ili drugih oblika za delove gradjevina najčešće za zidove. Uglavnom su poznata dva standardna oblika gradjevinskih opeka: cigle koje su manjih dimenzija i blokovi koji su većih dimenzija. I cigle i blokovi najčešće su paralelopipednog ili kockastog oblika i izradjuju se od punog materijala ili sa šupljinama unutar opeke. Materijal od kojih se izradjuju opeke može biti različit: od gline ili smeša koje sadrže glinu i'cement, preko betonskih, kamenih, do opeka sastavljenih od slojeva najrazličitijih materijala ili od stakla.
Kada su u pitanju blokovi poznata su dva tipa blokova od pečene gline koji su u tekućoj upotrebi za zidanje objekata. Prva vrsta blokova sa vertikalnim šupljinama i sa malim formatom i sa tankim (uskim) zidovima i druga vrsta blokova sa vertikalnim šupljinama sa većim formatom i nešto debljih zidova. Prva vrsta blokova uglavnom povlači probleme izolacije i opterećenja, dok druga vrsta blokova koristi više maltera za formiranje spojnica, ali obe vrste dovode do prepreka koje se manifestuju vrlo niskim faktorom pouzdanosti.
Generalno gledano svaka od poznatih opeka ima nedostatke koji se ogledaju u tome što nemaju karakteristike posebne prilagodjenosti koja bi olakšala sprovodjenje elektro i drugih instalacija, imaju mali koeficijent termoizolacije, poseduju slaba zvučna izolaciona svojstva, nisu uvek praktični i laki za zidanje i rukovanje, potrebna je veća upotreba maltera-vezivnog sredstva, i da bi u zidnoj konstrukciji povećali stabilnost i statiku gradjevine potrebno je zidati šire slojeve odnosno deblje zidove ili ih ojačavati betonskim nosačima.
Izlaganje suštine pronalaska
Pronalazak se odnosi na noseći blok za zidanje koji se sastoji od tela bloka koje je oblika paralelopipeda i u kome su izvedeni otvori takodje oblika paralelopipeda. Ose svih i otvora su paralelne kako medjusobno tako i sa centralnom osom bloka. Blok je odgovarajućih optimalnih dimenzija gde dužina, širina i visina su u takvom odnosu da je dužina dva puta veća od širine i dva i po puta veća od visine. Ono što predstavlja novost jeste poseban raspored svih otvora u tclu kako medjusobno tako i u odnosu na bočne stranice tela, kao i raspored i oblik žljebova i ispupčenja izvedenih na spoljašnjim - bočnim stranama bloka.
Noseći blok veoma je pogodan za zidanje nosećih zidova posebno sa aspekta aseizmičnosti zidanih objekata, kod kojih je od bitnog značaja ostvarivanje duktilnosti (opterećenje) zidnih struktura. Noseći blok je pre svega simbol brze, precizne i čvrste gradnje.
Osnovni ciljevi pronalaska su da se obezbede značajne tehničke prednosti u odnosu na poznata rešenja a to su: rešenje problema tzv. "hladnih mostova", znatno unapredjenje termo-izolacionih svojstava, zvučna svojstva kojima se termički rešavaju kompletni gradjevinski objekti a naročito spoljašnje površine kod kojih se pojavljuje kondenzacija vodene pare na zidovima.
Drugi cilj pronalaska je da se vertikalnim položajem šupljina u telu bloka doprinese većoj čvrstoći bloka i poboljšanju nosivosti objekta. Kako se blok povezuje sa malterom
(sintetički cementni lepak), i to na većim površinama po vertikali nego po horizontali, bitno se povećava otpornost na seizmičke potrese.
Značajnu prednost u konstrukciji i savremenom izgledu bloka predstavlja kombinacija i raspored šupljina koje imaju bolje osobine termičkih svojstava zidova za oko 80% u odnosu na rešenja koja se primenjuju u svetu.
Pronalazak - noseći blok za zidanje, prema ovoj prijavi patenta, ima više prednosti od kojih se nekoliko najhitnijih navode, i to : • poseduje posebne prilagodjenosti koje olakšavaju sprovodjenje elektro i drugih instalacija,
• poseduje visoki koeficijent termoizolacije,
• poseduje optimalna zvučna izolaciona svojstva,
• smanjena upotreba maltera-vezivnog sredstva,
• u zidnoj konstrukciji povećava stabilnost i statiku gradjevine,
• velika ušteda u vremenu zidanja,
• jednostavna konstrukcija,
• praktično neograničen vek trajanja,
• funkcionalno izuzetno praktičan,
• može se industrijski i serijski proizvoditi,
• geometrijski je idealno oblikovan i
• relativno niske proizvodne cene što ga čini ekonomski isplatljivim.
Kratak opis slika nacrta
J^adi-lakšeg-fazumevanja pronalaska - kao i zbog prikazivanja-kako—se--on—može— j3SJyiLritiji-pTaksH
• Slika 1 prikazuje noseći blok za zidanje, prema pronalasku, u
aksonometriji,
• Slika 2 prikazuje blok sa Slike 1 u horizontalnoj projekciji, odnosno u
pogledu sa gornje strane.
Detaljan opis pronalaska
Noseći blok za zidanje, prema pronalasku i Slikama 1 i 2, sastoji se od tela bloka 10, koje je oblika paralelopipeda, u kome su izvedeni otvori 14, 16, 18, 20. Svi otvori 14, 16, 18, 20 oblika su užih a dužih proreza, odnosno oblika paralelopipeda. Otvori 14, 16, 18 izvedeni su sa kraćim bočnim stranicama lučno zaobljenim. Centralne ose svih otvora 14, 16, 18, 20 su paralelne kako medjusobno tako i sa centralnom osom bloka.
Novo rešenje bloka, Slika 1, predstavlja poseban raspored otvora 14, 16, 18, 20 u telu kao i raspored i oblik žljebova 23 i ispupčenja 24 izvedenih na spoljašnjim - bočnim stranama bloka.
U telu 10 bloka, Slika 2, izvedena su dva središnja otvora 20, koji su u ovom prikazanom primeru, oblika paralelopipeda, i simetrično su postavljeni u odnosu na ose X-X i Y-Y. Središnje podužne ravni otvora 20 leže u centralnoj podužnoj ravni X-X bloka. Otvori 20 služe za (rukohvat) prihvatanje bloka sa dve ruke.
U prostoru izmedju otvora 20 i čija je širina jednaka širini otvora 20, nalaze se u dva reda po tri otvora 18. U produžetku svakog od otvora 20, odnosno u prostoru izmedju otvora 20 i kraćih bočnih strana tela 10 bloka, nalazi se po tri otvora 16 koji su nešto manjih dimenzija od otvora 18. Otvori 16, 18 su svojim dužim stranicama paralelni medjusobno a ujedno paralelni i sa podužnom ravni X-X. Središnje podužne ravni srednjih otvora 16, 18 i otvora 20 leže u centralnoj podužnoj ravni X-X bloka, dok otvori 16 i 18 levo i desno od srednjih otvora svojim središnjim podužnim ravnima leže u ravnima paralelnim ravni X-X.
Uz duže bočne stranice tela 10 bloka, tačnije izmedju centralnih otvora 16, 18, 20 i dužih bočnih stranica bloka, izvedeni su u dva pravilna reda otvori 14. Otvori 14 su svojim dužim stranicama paralelni medjusobno i sa poprečnom ravni Y-Y. U ovom primeru izvodjenja ima po 19 otvora 14 u svakom redu. Otvori 14 su većih dimenzija od otvora 16, 18, dok su otvori 18 većih dimenzija od otvora 16.
Posebna novost su žljebovi 23 i ispupčenja 24 koji su naizmenično izvedeni na spoljašnjim - bočnim stranama bloka. Površine i ivice žljebova 23 i ispupčenja 24 su izvedeni paralelno sa ravnima X-X i Y-Y. Površine koje spajaju ivice žljebova 23 i ispupčenja 24 se nalaze pod blagim nagibom usmerenim od ispupčenja 24 ka žljebu 23, a kako je to vidljivo na Slici 2.
Blok je odgovarajućih optimalnih dimenzija gde dužina, širina i visina najpovoljnije stoje u odnosu daje dužina dva puta veća od širine i dva i po puta veća od visine. Noseći blok je izgradjen na bazi pečene gline ili na bazi lakog betona.
Način industrijske ili druge primene pronalaska
Način primene pronalaska proističe na očigledan način iz prethodnog teksta i priloženih nacrta,. Način primene pronalaska proističe na očigledan način iz prethodnog teksta i priloženih nacrta, te ga nije potrebno posebno opisivati, odnosno za privrednu upotrebu prijavljenog pronalaska nisu potrebna neka posebna znanja, uputstva ili iskustva da bi se uspešno primenio pronalazak. Potrebna su i dovoljna samo ona znanja iz predmetne oblasti koja poseduje prosečan stručnjak za uspešnu primenu predmetnog pronalaska a na osnovu datog opisa. Sve konstrukcijske, funkcionalne i ekološke karakteristike pronalaska pronalazač je uspešno proverio na izradjenom prototipu.
Takodje, bilo kakva konstrukcijska poboljšanja ili izmene geometrijskih oblika koja bi bila u okviru prikazanog bloka i koja bi bila u cilju njegovog funkcionalnog poboljšanja, smatraju se da su obuhvaćena ovom prijavom.

Claims (9)

1 Noseći blok za zidanje/,naznačen ti me, što su u telu (10), oblika paralelopipeda, izvedeni otvori (14, 16, 18, 20), što su otvori (14, 16, 18, 20) oblika paralelopipeda, pri čemu su kraće bočne stranice otvora (14, 16, 18) lučno zaobljene, što su otvori (16, 18, 20) svojim dužim stranicama paralelni sa podužnom ravni X-X, dok su otvori (14) svojim dužim stranicama paralelni sa poprečnom ravni Y-Y, što su centralne ose otvora (14, 16, 18, 20) paralelne kako medjusobno tako i sa centralnom osom bloka i što su na spoljašnjim - bočnim stranama tela (10) naizmenično izvedeni žljebovi (23) i ispupčenja (24).
2. Noseći blok prema zahtevu1, naznačen t i m e, što su utelu (10) izvedena dva središnja otvora (20) postavljena simetrično u odnosu na ose X-X i Y-Y.
3. Noseći blok prema zahtevu 1,naznačen time,što se u prostoru izmedju otvora (20), čija je širina jednaka širini otvora (20), nalaze u dva reda po tri otvora (18).
4. Noseći blok prema zahtevu1, naznačen t i m e , što se uprodužetku svakog od otvora (20), odnosno u prostoru izmedju otvora (20) i kraćih bočnih strana tela (10) bloka, nalazi po tri otvora (16).
5. Noseći blok prema zahtevima2, 2 i A, naznačen t i m e , štosredišnje podužne ravni srednjih otvora (16, 18) i otvora (20) leže u centralnoj podužnoj ravni X-X bloka, dok otvori (16, 18) levo i desno od srednjih otvora (16, 18) svojim središnjim podužnim ravnima leže u ravnima paralelnim ravni X-X.
6. Noseći blok prema zahtevu 1,naznačen t i m e ,što su izmedju centralno postavljenih otvora(16,18,20) i dužih bočnih stranica tela (10) bloka, u dva pravilna reda po 19 komada, izvedeni otvori (14), pri čemu su otvori (14) svojim dužim stranicama paralelni medjusobno i paralalelni sa poprečnom ravni Y-Y.
7. Noseći blok prema bilo kom od prethodnihzahteva , naznačen ti me,što su otvori (14) većih dimenzija od otvora (18), dok su otvori (18) većih dimenzija od otvora (16).
8. Noseći blok prema zahtevu\ , naznačen t i m e ,što su površine i ivice žljebova (23) odnosno ispupčenja (24) izvedeni paralelno sa ravnima X-X i Y-Y i što se površine koje spajaju ivice žljebova (23) i ispupčenja (24) nalaze pod nagibom usmerenim od ispupčenja (24) ka žljebu (23).
9. Noseći blok prema zahtevu1, naznačen ti me, štodužina, širina i visina tela (10) stoje u najpovoljnijem odnosu da je dužina dva puta veća od širine i dva i po puta veća od visine.
RS20200782A 2011-12-20 2012-12-18 Modifikovani polipeptidi za bispecifične skelete antitela RS60499B1 (sr)

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PCT/US2012/070310 WO2013096291A2 (en) 2011-12-20 2012-12-18 Modified polypeptides for bispecific antibody scaffolds
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