1. A storage-stable pharmaceutical composition, comprising an aqueous solution of:
at least an antibody-derived therapeutically active protein chosen amongst antibody, nanobody or fusion protein;
an amount effective to stabilize said antibody-derived therapeutically active protein of at least one lauryldimethylamineoxide andor of one of its amine oxide analogs.
2. The pharmaceutical composition of claim 1, wherein the analogs of lauryldimethylamineoxide are chosen amongst the amine oxide analogs of formula I ;
wherein,
m represents an integer comprised in the interval from 0 to 17, 0\u2266m\u226617,
n represents an integer comprised in the interval from 0 to 17, 0\u2266n\u226617,
a represents an integer equal to 0 or 1,
9\u2266m+n\u226617,
If m=0, then a=0
F represents a function chosen in the group constituted by the functions amide, ester, carbamate and urea,
R1 and R2, identical or different, represent alkyl chains comprising from 1 to 4 carbon atoms.
3. The pharmaceutical composition according to claim 2, wherein a=0 and m=0 and the amine oxide is chosen amongst the compounds of formula II:
wherein,
n represents an integer comprised in the interval from 9 to 17, 9\u2266n\u226617,
R1 and R2, identical or different, represent alkyl chains comprising from 1 to 4 carbon atoms.
4. The pharmaceutical composition according to claim 1, wherein the concentration of the at least one lauryldimethylamineoxide andor amine oxide analogs is from 0.01 to 100 mM.
5. The pharmaceutical composition according to claim 1, wherein the concentration of the at least one lauryldimethylamineoxide andor amine oxide analogs is from 0.1 to 10 mM.
6. The pharmaceutical composition according to claim 1, wherein the at least one amine oxide analogs is N,N-Dimethyldecylamine N-oxide (CAS 2605-79-0).
7. The pharmaceutical composition according to claim 1, wherein the at least one amine oxide analogs is N,N-Lauryldimethylamine N-oxide (CAS 1643-20-5).
8. The pharmaceutical composition according to claim 1, wherein the at least one amine oxide analogs is N,N-Dimethyltetradecylamine N-oxide (CAS 3332-27-2).
9. The pharmaceutical composition according to claim 1, wherein the at least one amine oxide analogs is N-2-(dimethylnitroyl)ethyldodecanamide (CAS 86321-42-8).
10. The pharmaceutical composition according to claim 1, further comprising an additional surfactant.
11. The pharmaceutical composition according to claim 1, wherein said composition has a pH that is in the range from 5 to 8.
12. The pharmaceutical composition according to claim 1, wherein said composition has a pH that is in the range from 5.5 to 7.8.
13. The pharmaceutical composition according to claim 1, wherein said composition has an osmolality in the range from 200 to 600 mOsmkg.
14. The pharmaceutical composition according to claim 1, wherein said composition has an osmolality in the range from 200 to 500 mOsmkg.
15. The pharmaceutical composition according to claim 1, wherein the antibody-derived therapeutically active protein is an antibody.
16. The pharmaceutical composition according to claim 1, wherein the antibody-derived therapeutically active protein is a nanobody.
17. The pharmaceutical composition according to claim 1, wherein the antibody-derived therapeutically active protein is a fusion protein.
18. The pharmaceutical composition according to claim 1, wherein the concentration of the antibody-derived therapeutically active protein is from 1 to 350 mgmL.
19. A pharmaceutical container, comprising a hermetically sealed vessel and the pharmaceutical composition of claim 1.
20. The pharmaceutical container of claim 21, where in the vessel is a vial, bottle, pre-filled syringe or pre-filled auto-injector.
21. (canceled)
22. (canceled)
23. A method of providing storage stability to an aqueous pharmaceutical formulation of an antibody-derived therapeutically active protein, comprising admixing under sterile conditions in an aqueous solution an antibody-derived therapeutically active protein, and amount effective to stabilize said antibody-derived therapeutically active protein of at least one lauryldimethylamineoxide andor of one of its amine oxide analogs.
24. Method according to claim 22, wherein the at least one amine oxide analog is chosen amongst the amine oxides of formula I:
wherein
m represents an integer comprised in the interval from 0 to 17, 0\u2266m\u226617,
n represents an integer comprised in the interval from 0 to 17, 0\u2266n\u226617,
a represents an integer equal to 0 or 1,
9\u2266m+n\u226617,
if m=0, then a=0
F represents a function chosen in the group constituted by the functions amide, ester, carbamate and urea,
R1 and R2, identical or different, represent alkyl chains comprising from 1 to 4 carbon atoms.
25. A method of increasing the shelf life of an aqueous pharmaceutical formulation of an antibody-derived therapeutically active protein, comprising admixing under sterile conditions in an aqueous solution an antibody-derived therapeutically active protein, and amount effective to stabilize said antibody-derived therapeutically active protein of at least one lauryldimethylamineoxide andor of one of its amine oxide analogs.
26. A method according to claim 25, wherein the at least amine oxide analog is chosen amongst the amineoxides of formula I:
wherein
m represents an integer comprised in the interval from 0 to 17, 0\u2266m\u226617,
n represents an integer comprised in the interval from 0 to 17, 0\u2266n\u226617,
a represents an integer equal to 0 or 1,
9\u2266m+n\u226617,
If m=0, then a=0
F represents a function chosen in the group constituted by the functions amide, ester, carbamate and urea,
R1 and R2, identical or different, represent alkyl chains comprising from 1 to 4 carbon atoms.
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. A method for correcting a Z-height measurement determined by a machine vision inspection system based on a current focus region of interest, the method comprising:
determining the Z-height measurement based on the current focus region of interest;
determining orientation angle content characteristics for the image content in the current focus region of interest;
accessing Z-height error calibration data that includes a characterization of a variation in Z-height measurement results based on a focus region of interest used for calibration, in relation to a variation in an orientation angle of anisotropic image content in the focus region of interest used for calibration;
determining a Z-height error correction value based on the orientation angle content characteristics for the image content in the current focus region of interest and the Z-height error calibration data; and
correcting the Z-height measurement using the Z-height error correction value.
2. The method of claim 1, wherein the Z-height error correction value corrects at least one of a) an astigmatism error component, b) an astigmatism error component and a static optical error component, and c) an anisotropic error, included in the Z-height measurement.
3. The method of claim 1, wherein determining the Z-height measurement based on the current focus region of interest comprises using one of a) a surface-type auto-focus tool, and b) an edge-type auto-focus tool included in the machine vision inspection system.
4. The method of claim 1, wherein the Z-height error calibration data comprises respective sets of data corresponding to a plurality of respective locations within a field of view of the machine vision inspection system, wherein for each of the respective locations, the respective set of error calibration data characterizes a variation in Z-height measurement results based on a focus region of interest used for calibration at that location, in relation to a variation in an orientation angle of anisotropic image content in the focus region of interest used for calibration at that location.
5. The method of claim 4, wherein determining a Z-height error correction value based on the orientation angle content characteristics for the image content in the current focus region of interest and the Z-height error calibration data comprises:
identifying a plurality of the respective sets of error calibration data corresponding to respective locations that are closest to a location of the current focus region of interest;
estimating an interpolated set of error calibration data corresponding to the location of the current focus region of interest based on the identified plurality of the respective sets of error calibration data; and
determining the Z-height error correction value based on the orientation angle content characteristics for the image content in the current focus region of interest and the interpolated set of error calibration data corresponding to the location of the current focus region of interest.
6. The method of claim 5, wherein the identified plurality of respective sets of error calibration data comprise all the respective sets of error calibration data.
7. The method of claim 4, wherein the Z-height error calibration data comprises a first group of respective sets of data corresponding to a plurality of respective locations within a field of view that corresponds to a first optical configuration of the machine vision inspection system, and at least a second group of respective sets of data corresponding to a plurality of respective locations within a field of view that corresponds to at least a second optical configuration of the machine vision inspection system.
8. The method of claim 1, wherein:
the variation in an orientation angle comprises a set of orientation angles, separated by evenly spaced steps, over a range from zero degrees up to at least 180 degrees minus one step;
the Z-height error calibration data comprises a respective error value corresponding to each respective orientation angle of the set of orientation angles, each respective error value comprising one of a) an astigmatism error component value, b) an astigmatism error component value plus a static optical error component value, and c) an anisotropic error value; and
determining the Z-height error correction value based on the orientation angle content characteristics for the image content in the current focus region of interest and the Z-height error calibration data comprises:
weighting the respective error value corresponding to each respective orientation angle by a weighting factor determined based on the orientation angle content characteristics for the image content in the current focus region of interest; and
summing the weighted respective error values to determine the Z-height error correction value.
9. The method of claim 8, wherein:
determining orientation angle content characteristics for the image content in the current focus region of interest comprises:
determining a gradient direction and a gradient magnitude corresponding to each of a plurality of pixels distributed throughout the focus region of interest; and
determining a histogram having a set of orientation angle bins corresponding to the set of orientation angles, each bin having a bin value determined at least partly by the number of pixels from the plurality of pixels distributed throughout the focus region of interest that have a gradient direction corresponding to the orientation angle range of that bin, and
weighting the respective error value corresponding to each respective orientation angle by the weighting factor comprises multiplying the respective error value corresponding to each respective orientation angle by a value that depends on the bin value corresponding to that respective orientation angle.
10. The method of claim 9, wherein the image content in the focus region of interest is filtered to remove at least the highest spatial frequency, before the gradient direction and magnitude are determined.
11. The method of claim 9, wherein a pixel from the plurality of pixels distributed throughout the focus region of interest is not included in the number of pixels that at least partly determines the bin value if the absolute value of its gradient is smaller than a predetermined noise threshold.
12. The method of claim 9, wherein each bin value also depends at least partly on the absolute value of the gradient for pixels included in the number of pixels that at least partly determines the bin value.
13. The method of claim 9, wherein the histogram is normalized so that the sum of its bin values is 1.0.
14. A method for providing Z-height error calibration data usable to correct Z-height measurements determined by a machine vision inspection system, the method comprising:
(a) positioning a focus region of interest used for calibration at a calibration location in a field of view of the machine vision inspection system;
(b) providing anisotropic image content used for calibration;
(c) positioning the anisotropic image content in the focus region of interest used for calibration;
(d) providing a variation in an orientation angle of the anisotropic image content in the focus region of interest used for calibration;
(e) determining Z-height measurement results based on the focus region of interest used for calibration, the Z-height measurement results including a variation in relation to the variation in the orientation angle of the anisotropic image content in the focus region of interest used for calibration;
(f) determining Z-height error calibration data corresponding to the current calibration location in a field of view, the Z-height error calibration data including a characterization of the variation in Z-height measurement results, in relation to a variation in the orientation angle of the anisotropic image content in the focus region of interest used for calibration; and
(g) storing the Z-height error calibration data corresponding to the current calibration location in a field of view in a storage medium accessible by the machine vision inspection system.
15. The method of claim 14, wherein the characterization of the variation in Z-height measurement results characterizes at least one of a) an astigmatism error component, b) an astigmatism error component and a static optical error component, and c) an anisotropic error, included in the Z-height measurement results.
16. The method of claim 14, wherein providing a variation in an orientation angle of the anisotropic image content in the focus region of interest comprises providing a set of orientation angles, separated by evenly spaced steps, over a range from zero degrees up to at least 180 degrees minus one step;
17. The method of claim 16, wherein step (b) comprises providing a calibration target, the calibration target comprising a set of respective anisotropic target elements that provide the anisotropic image content at respective orientation angles, the respective orientation angles including the set of orientation angles separated by evenly spaced steps, over a range from zero degrees up to at least 180 degrees minus one step.
18. The method of claim 17, wherein:
step (d) comprises positioning each of the respective anisotropic target elements corresponding to the set of orientation angles separated by evenly spaced steps over a range from zero degrees up to at least 180 degrees minus one step, such that its anisotropic image content appears in the focus region of interest used for calibration, at its respective orientation angle; and
step (e) comprises determining a Z-height measurement result for each of the positioned respective anisotropic target elements corresponding to the set of orientation angles separated by evenly spaced steps over a range from zero degrees up to at least 180 degrees minus one step.
19. The method of claim 18, wherein determining a Z-height measurement result comprises performing an autofocus operation based on the focus region of interest used for calibration.
20. The method of claim 18, further comprising:
determining a true Z-height for each of the positioned respective anisotropic target elements; and
determining an anisotropic error corresponding to each of the positioned respective anisotropic target elements, based on the Z-height measurement result and the true Z-height determined for each of the positioned respective anisotropic target elements,
wherein step (f) comprises determining Z-height error calibration data that includes a characterization of the anisotropic error, in relation to the set of orientation angles separated by evenly spaced steps over a range from zero degrees up to at least 180 degrees minus one step.
21. The method of claim 20, wherein:
the calibration target further comprises a set of respective isotropic target elements that provide isotropic image content; and
the method further comprises
positioning each member of the set of respective isotropic target elements such that its isotropic image content appears in the focus region of interest used for calibration; and
determining a set of isotropic Z-height measurements corresponding to the positioned members of the set of respective isotropic target elements, and
using the set of isotropic Z-height measurements in determining the true Z-height for each of the positioned respective anisotropic target elements.
22. The method of claim 14, wherein in step (f) determining Z-height error calibration data comprises:
determining a set of respective anisotropic errors that correspond to a set of respective orientation angles used while determining the Z-height measurement results of step (e); and
determining anisotropic error calibration data that includes a representation of the respective anisotropic errors in relation to the respective orientation angles.
23. The method of claim 22, wherein:
steps (a) through (g) are repeated at a plurality of different calibration locations in the field of view;
an average value of the respective anisotropic errors from all the calibration locations is subtracted from each of the respective anisotropic errors from all the calibration locations to provide respective resulting values; and
in the anisotropic error calibration data, the respective resulting values are used in the representation of the respective anisotropic errors in relation to the respective orientation angles.
24. The method of claim 14, wherein steps (a) through (g) are repeated at a plurality of different calibration locations in the field of view.
25. The method of claim 24, wherein the method of claim 24 is repeated for a plurality different optical configurations of the machine vision inspection system.
26. A calibration target used in a method for providing Z-height error calibration data for machine vision inspection system, the calibration target comprising:
a flat substrate; and
a first set of respective anisotropic target elements arranged on the flat substrate, each respective anisotropic target element comprising a similar anisotropic feature,
wherein the similar anisotropic feature is arranged at different respective orientation angles in different respective anisotropic target elements.
27. The calibration target of claim 26 wherein the different respective orientation angles include a set of orientation angles separated by evenly spaced steps, over a range from zero degrees up to at least 180 degrees minus one step.
28. The calibration target of claim 27, wherein the evenly spaced steps are 15 degrees apart, at most.
29. The calibration target of claim 28, wherein the evenly spaced steps are 7.5 degrees apart, at most.
30. The calibration target of claim 27, wherein the evenly spaced steps comprise a step size that is one of 5 degrees, 7.5 degrees, and 15 degrees.
31. The calibration target of claim 26, wherein each of the anisotropic target elements is designed to be slightly larger than the field of view of an optical configuration intended to be calibrated by the anisotropic target element.
32. The calibration target of claim 26, wherein the similar anisotropic feature comprises a pattern of parallel lines.
33. The calibration target of claim 26, wherein the similar anisotropic feature comprises one of a) a pattern of parallel lines, b) a texture pattern, c) a striated texture pattern, and d) a single border between a lighter region and a darker region.
34. The calibration target of claim 26, further comprising a first set of respective isotropic target elements.
35. The calibration target of claim 34, wherein each of the respective isotropic target elements comprises a pattern of alternating concentric lighter circles and darker circles.
36. The calibration target of claim 34, wherein the first set of respective isotropic target elements is interspersed with the first set of respective anisotropic target elements.
37. The calibration target of claim 36, wherein the first set of respective isotropic target elements and the first set of respective anisotropic target elements form a first group of elements of the calibration target, and the calibration target further comprises a second group of elements similar to the first group of elements, but wherein all dimensions are scaled by a factor of less than 1.0, relative to the first group of elements.
38. The calibration target of claim 26, wherein the first set of respective anisotropic target elements form a first group of elements of the calibration target, and the calibration target further comprises a second group of elements similar to the first group of elements, but wherein all dimensions are scaled by a factor of 0.5 or less, relative to the first group of elements.