1. A method for transmitting an uplink signal by a user equipment (UE) in a wireless communication system, the method comprising:
receiving, by the UE, a physical downlink control channel (PDCCH) via one or more resource units;
receiving, by the UE, a physical downlink shared channel (PDSCH) indicated by the received PDCCH; and
transmitting, by the UE, a physical uplink control channel (PUCCH) using a PUCCH resource in response to the received PDSCH,
wherein an index of the PUCCH: resource is determined by adding a first index offset and a second index offset to a lowest index of the one or more resource units, and
wherein the first index offset is signaled via the PDCCH and the second index offset is signaled via higher layer signaling.
2. The method of claim 1, wherein the PDSCH carries a downlink data signal and the PUCCH carries an acknowledgementnegative-acknowledgement (ACKNACK) signal for the downlink data signal.
3. The method of claim 1, wherein the first index offset is signaled through downlink control information (DCI) which is carried by the PDCCH.
4. The method of claim 1, wherein each of the one or more resource units corresponds to a control channel element (CCE).
5. The method of claim 4, wherein the lowest index corresponds to a lowest CCE index used to construct the PDCCH.
6. The method of claim 1, wherein the second index offset is signaled through an RRC message.
7. A user equipment (UE) configured to transmit an uplink signal in a wireless communication system, the UE comprising:
a radio frequency (RF) unit; and
a processor configured to:
receive a physical downlink control channel (PDCCH) via one or more resource units,
receive a physical downlink shared channel (PDSCH) indicated by the received PDCCH, and
transmit a physical uplink control channel (PUCCH) using a PUCCH resource in response to the received PDSCH,
wherein an index of the PUCCH resource is determined by adding a first index offset and a second index offset to a lowest index of the one or more resource units, and
wherein the first index offset is signaled via the PDCCH and the second index offset is signaled via higher layer signaling.
8. The UE of claim 7, wherein the PDSCH carries a downlink data signal and the PUCCH carries an acknowledgementnegative-acknowledgement (ACKNACK) signal for the downlink data signal.
9. The UE of claim 7, wherein the first index offset is signaled through downlink control information (DCI) which is carried by the PDCCH.
10. The UE of claim 7, wherein each of the one or more resource units corresponds to a control channel element (CCE).
11. The UE of claim 10, wherein the lowest index corresponds to a lowest CCE index used to construct the PDCCH.
12. The UE of claim 7, wherein the second index offset is signaled through an RRC message.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-15. (canceled)
16. A polymorphic form of arformoterol tartrate, designated as form D, which is characterized by at least one of the following:
(i) a powder X-ray diffraction pattern having peaks at 6.8, 13.3, 13.6, 13.8, 14.1, 18.2, 18.7, 20.0\xb10.2 degrees two theta; or
(ii) a DSC thermogram showing an endothermic peak with an onset at approximately 119-120\xb0 C., and a maximum at approximately 129-131\xb0 C., followed by an exothermic peak with a maximum at approximately 137-138\xb0 C.; wherein the DSC thermogram of form D has a further endothermic peak with an onset at approximately 168-170\xb0 C.
17. The polymorphic form of arformoterol tartrate form D according to claim 1, which has a powder X-ray diffraction pattern further comprising one or more additional peaks at 7.4, 15.9, 25.1 and 25.8\xb10.2 degrees two theta.
18. The polymorphic form of arformoterol tartrate form D according to claim 1, having a powder X-ray diffraction pattern in accordance with FIG. 1.
19. The polymorphic form of arformoterol tartrate form D according to claim 1, having at least 30% (ww) of form D, preferably from 40% to 90% (ww), more preferably from 50% to 80% (ww) relative to the total weight of form D and polymorph A.
20. The polymorphic form of arformoterol tartrate form D according to claim 1, having between 40 and 50% of the known polymorph A.
21. A process for preparing arformoterol tartrate form D from arformoterol base, the process comprising the steps of:
a) providing a mixture of arformoterol base with an alcohol, or with a combination of acetonitrile and an alcohol, at a temperature between 15 and 60\xb0 C.;
b) adding a solution of L-tartaric acid in a solvent selected from an alcohol, water and mixtures thereof, to the mixture obtained in step (a);
c) cooling the mixture of step (b) to a temperature between 30 and 15\xb0 C., when necessary, followed by stirring to obtain a solid;
d) further cooling the mixture of step (c) to a temperature between 0 and 10\xb0 C.; and
e) collecting the crystals obtained in step (d), and drying the crystals under inlet air pressure and at a temperature between 30 and 50\xb0 C. to yield arformoterol tartrate form D.
22. The process according to the claim 21, wherein the mixture provided in step (a) is a mixture of arformoterol base with an alcohol, selected from methanol, ethanol, or isopropanol; preferably methanol or ethanol; more preferably methanol.
23. The process according to claim 21, wherein the solution used in step (b) is a solution of L-tartaric acid in an alcohol, selected from methanol, ethanol, or isopropanol; preferably methanol or ethanol; more preferably methanol.
24. The process according to the claim 21, wherein the alcohol used in steps (a) and (b) is the same and is selected from methanol, ethanol and isopropanol.
25. The process according to claim 24, wherein the preferred alcohol used in step (a) andor step (b) is methanol or ethanol.
26. The process according to claim 21, wherein the ratio of the alcoholacetonitrile used in step (a) is of at least 1:0.1, preferably between 1:1 and 1:5.
27. The process according to claim 21, wherein the mixture of step (a) is preferably at a temperature between 20 and 60\xb0 C.
28. The process according to claim 21, wherein the temperature of the cooling carried out in step (d) is preferably between 0 and 5\xb0 C.
29. A process for the preparation of a mixture of form D and polymorph A of arformoterol tartrate, optionally from other polymorphic forms of arformoterol tartrate, and comprising the steps of:
a) providing a mixture of arformoterol tartrate and a solvent which is a mixture of an alcohol and water, at a temperature between 60 and 70\xb0 C.;
b) cooling the mixture obtained in step (a) to a temperature between 50 and 55\xb0 C.;
c) adding acetonitrile to the mixture obtained in step (b) until a suspension is obtained;
d) cooling the suspension obtained in step (c) while stirring to a temperature between 10 and 30\xb0 C. to obtain a solid; and
e) collecting the crystals obtained in step (d) and drying the crystals under vacuum at a pressure between 0.75 and 40 mm Hg and at a temperature between 50 and 90\xb0 C.;
wherein the ratio of alcohol: water used in step (a) is over 1:1 and up to 5:1, wherein the mixture of form D and polymorph A of arformoterol tartrate so prepared is according to claim 19.
30. A pharmaceutical composition comprising the arformoterol tartrate according to claim 1 and at least one pharmaceutically acceptable excipient or carrier.
31. A method of effecting bronchodilation, the method comprising the administration, to a subject in need of such treatment, of a therapeutically effective amount of arformoterol tartrate according to claim 1.
32. A method of effecting bronchodilation, the method comprising the administration, to a subject in need of such treatment, of a pharmaceutical composition according to claim 19.