WO2016189491A1

WO2016189491A1 - Novel formulation

Info

Publication number: WO2016189491A1
Application number: PCT/IB2016/053093
Authority: WO
Inventors: Ulla Tove Lashmar; Ahmed YASIN
Original assignee: GlaxoSmithKline Intellectual Property Development Ltd
Current assignee: GlaxoSmithKline Intellectual Property Development Ltd
Priority date: 2015-05-28
Filing date: 2016-05-26
Publication date: 2016-12-01
Anticipated expiration: 2017-11-28

Abstract

The present invention relates to formulations containing antibodies to β-amyloid for treating diseases or disorders affecting the eye or optic nerve characterised by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration (including geographic atrophy) and glaucoma type diseases and β-amyloid dependent cataract formation, with antigen binding proteins that bind β-amyloid peptide and in particular human β-amyloid peptide.

Description

Novel Formulation

Field of the invention

The present invention relates to an antibody formulation for treating diseases or disorders affecting the eye or optic nerve characterised by elevated β-amyloid levels or β-amyloid deposits, particularly age related macular degeneration and glaucoma type diseases and β-amyloid-dependent cataract formation, with antigen binding proteins that bind β-amyloid peptide and in particular human β-amyloid peptide. Other aspects of the present invention will be apparent from the description below.

Background of the invention The presence of β-amyloid (Αβ) in drusen in AMD and plaques in Alzheimer's disease, as well as the potential of Αβ to activate complement locally in both diseases, suggests that the pathogenesis of geographic atrophy (GA) and Alzheimer's disease (AD) may share common elements. Thus Αβ is a common therapeutic target and an anti- Αβ antibody is believed to act by a postulated 'peripheral sink' mode of action resulting in an overall shift of Αβ from the brain or eye into the plasma compartment. This shift, in turn, may translate into arrest or delay of the cognitive decline in AD patients, slowing of the progression of GA and loss of vision in AMD patients, and possibly even the slowing the transition to both GA and neovascular AMD from earlier stages of AMD. Our copending application WO 2009040336 (which is hereby incorporated by reference in its entirety) discloses anti^-amyloid antibodies which are useful in the treatment of disease or disorder affecting the eye or optic nerve characterized by β-amyloid levels or β-amyloid deposits, more in particular AMD (including geographic atrophy), glaucoma or β-amyloid dependent cataract formation. The pharmaceutical use of antibodies has increased over the past years. In many instances such antibodies are injected via the intravenous (IV) route. Unfortunately the amount of antibody that can be injected via the intravenous route is limited by the physico-chemical properties of the antibody, in particularly by its solubility and stability in a suitable liquid formulation and by the volume of the infusion fluid. Alternative administration pathways are subcutaneous or intramuscular injection. These injection pathways require high protein concentration in the final solution to be injected. Accordingly, there is a desire to provide highly concentrated, stable pharmaceutical formulations of therapeutically active antigen binding proteins such as antibodies for subcutaneous injection. The advantage of subcutaneous injections is that it allows the medical practitioner to perform it in a rather short intervention with the patient.

Moreover the patient can be trained to perform the subcutaneous injection by himself. Such self-administration is particularly useful during maintenance dosing because no hospital care is needed (reduced medical resource utilization). Usually injections via the subcutaneous route are limited to approximately 1.2 ml. For patients requiring multiple doses, several unit dose formulations can be injected at multiple sites of the body surface. Thus, there is a consistent need to develop pharmaceutical formulations for antibodies tailored to individual antibodies, because study after study has shown that a composition must be formulated to be tailored to particular antibodies to achieve maximum stabilities.

Summary of the invention

The present invention generally relates to a high concentration formulation for delivering an anti-P-amyloid antibody for treating a human patient afflicted with a disease or disorder affecting the eye or optic nerve characterised by elevated β- amyloid levels or β-amyloid deposits, in particular AMD (age-related macular degeneration, (including geographic atrophy), glaucoma or β-amyloid dependent cataract formation. The formulation of the present invention discussed below achieves a high degree of thermal and shear stability and is particularly suited for long term storage for intramuscular and subcutaneous and intra-muscular delivery, among others.

In one embodiment, the invention relates to an anti-P-amyloid antibody formulation comprising a therapeutically effective amount of an anti-P-amyloid antibody, wherein the formulation further comprises 10 to 100 mM sodium acetate, 25 to 100 mM sodium chloride, 0.5 to 5% arginine free base, 0.02 to 0.2 mM EDTA, 0.01 to 0.2 % polysorbate 80 and adjusted to pH between 5.0 and 7.0 (preferably between 5.0 and 6.0, more preferably between 5.3 to 5.7, and even more preferably 5.5).

In another embodiment, the invention relates to an anti-P-amyloid antibody formulation comprising an anti-P-amyloid antibody in the concentration range of 20- 300 mg/mL (for example, 50mg/mL, lOOmg/mL, and 150mg/mL), wherein the formulation further comprises 50 mM sodium acetate, 51 mM sodium chloride, 1% arginine free base, 0.05 mM EDTA, 0.02% polysorbate 80, and adjusted to pH 5.5. In another embodiment, the invention relates to an anti-β -amyloid antibody formulation wherein the anti-P-amyloid antibody is present in an amount of about 50 mg/mL, lOOmg/mL, 150mg/mL, 20-300 mg/mL, 50-300 mg/mL, 100-300 mg/mL, 150-300 mg/mL, 200-300 mg/mL, or 250-300 mg/mL. In another embodiment, the invention relates to an anti-P-amyloid antibody formulation wherein sodium acetate is present in an amount of about 50mM, 40mM, 45mM, 55mM, or 60mM. In other embodiments, the sodium acetate may be present in an amount of 10 to 100 mM, 20 to 100 mM, 30 to 100 mM, 40 to 100 mM, 50 to 100 mM, 60 to 100 mM, 70 to 100 mM, 25 to 80 mM, or 30 to 70 mM.

In yet another embodiment, the invention relates to an anti-β -amyloid antibody formulation wherein acetic acid is present (about 100 mM acetic acid) to adjust the formulation to about pH 5.5. In other embodiments, the pH may be adjusted to pH 5.0, 5.5, 6.0, 6.5 or 7.0. In yet other embodiments of the invention, NaOH or HC1 is used to adjust the pH to 5.0, 5.5, 6.0, 6.5 or 7.0.

In yet another embodiment, the invention relates to an anti-β -amyloid antibody formulation wherein sodium chloride is present in an amount of about 51mM, 45mM, 46mM, 47mM, 48mM, 49mM, 50mM, 52mM, 53mM, 54mM, 55mM. In other embodiments, the sodium chloride may be present in an amount of 25 to 100 mM, 35 to 90 mM, 45 to 80 mM, 25 to 70 mM, or 45 to 70 mM.

In another embodiment, the invention relates to an anti-P-amyloid antibody formulation wherein arginine free base is present in an amount of about 1%, 0.7%, 1.3%, or 2.0%). In other embodiments, the arginine free base may be between 0.5 and 5.0%, 0.5 to 2.0%, 0.5 to 2.5%, 0.5 to 3.0%, 0.5 to 3.5%, 0.5 to 4.0%, or 0.5 to 4.5%.

In another embodiment, the invention relates to an anti-P-amyloid antibody formulation wherein EDTA is present in an amount of about 0.05 mM, 0.03 mM, 0.04 mM, or 0.06 mM. In other embodiments, the EDTA may be present in an amount of 0.02 mM - 0.2 mM, 0.02 mM - 0.1 mM, 0.02 mM - 0.15 mM, 0.04 mM - 0.1 mM, 0.03 mM - 0.15 mM, or 0.03 mM - 0.2 mM. In another embodiment, the invention relates to an anti-P-amyloid antibody formulation wherein polysorbate 80 is present in an amount of about 0.02%, 0.015%), or 0.025%). In other embodiments, the polysorbate 80 may be present in an amount of 0.01 - 0.2%, 0.01 - 0.15%, 0.02 - 0.2%, 0.02 - 0.15%, 0.01 - 0.25%, or 0.01 - 0.05%.

In yet another embodiment, the invention relates to a method of treating a human patient afflicted with a disease or disorder affecting the eye or optic nerve

characterised by elevated β-amyloid levels or β-amyloid deposits, in particular AMD (including geographic atrophy), glaucoma or β-amyloid dependent cataract formation with an anti-P-amyloid antibody formulation comprising a therapeutically effective amount of an anti-P-amyloid antibody, wherein the formulation further comprises 10 to 100 mM sodium acetate, 25 to 100 mM sodium chloride, 0.5 to 5% arginine free base, 0.02 to 0.2 mM EDTA, 0.01 to 0.2 % polysorbate 80 and adjusted to pH 5.0 to 7.0 and wherein the antibody formulation is administered orally, parenterally, intranasally, vaginally, rectally, lingually, sublingually, bucally, transdermally, intravenously, or subcutaneously to a mammal.

characterised by elevated β-amyloid levels or β-amyloid deposits, in particular AMD (including geographic atrophy), glaucoma or β-amyloid dependent cataract formation with an anti^-amyloid antibody formulation comprising an anti^-amyloid antibody in the concentration range of 20-300 mg/mL, wherein the formulation further comprises 50 mM sodium acetate, 51 mM sodium chloride, 1%> arginine free base, 0.05 mM EDTA, 0.02% polysorbate 80, and adjusted to pH 5.5. In yet another embodiment, the present invention relates to a pharmaceutical formulation according to any above embodiments for use in therapy.

In yet another embodiment, the present invention relates to a pharmaceutical formulation according to any above embodiments for the treatment of a disease or disorder amenable to treatment with an anti-P-amyloid antibody.

In yet another embodiment, the present invention relates to a pharmaceutical formulation according to any above embodiments for use in the treatment of disease or disorder effecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits.

In yet another embodiment, the disease or disorder above is age-related macular degeneration (AMD), geographic atrophy, glaucoma or β-amyloid dependent cataract formation.

In yet another embodiment, the present invention relates to the use of the

pharmaceutical formulation according to any preceding embodiments in the manufacture of a medicament for use in the treatment of a disease or disorder effecting the eye or optic nerve characterized by elevated β-amyloid levels or β- amyloid deposits.

In yet another embodiment, the use of the pharmaceutical formulation above in which the disease or disorder is age-related macular degeneration (AMD), geographic atrophy, glaucoma or β-amyloid dependent cataract formation.

In another aspect the present invention provides for a kit comprising one or more vials containing the formulation according to the present invention and instructions for subcutaneous or intramuscular administration of the formulation to a patient. In one embodiment an anti-P-amyloid antibody of the invention refers to an antibody having a variable heavy and variable light region comprising the following CDRs:

CDRH1 : DNGMA (SEQ ID No: 1)

CDRH2: FISNLAYSIDYADTVTG (SEQ ID No:2)

CDRH3 : GTWFAY (SEQ ID No:3)

within a heavy chain variable region and;

CDRL1 : RVSQSLLHSNGYTYLH (SEQ ID No:4)

CDRL2: KVSNRFS (SEQ ID No:5)

CDRL3 : SQTRHVPYT (SEQ ID No:6)

within a light chain variable region.

In a further embodiment, the anti-β -amyloid antibody of the present invention refers to an antibody with a heavy variable region and light a variable region of SEQ ID NOs: 7 and 8, respectively.

Yet in another embodiement, the anti-P-amyloid antibody of the present invention refers to an antibody having heavy and light chains of SEQ ID NOs: 9 and 10 respectively, which is hereinbelow referred to as Antibody A.

Description of Figures

Figure 1. HSDSC heat flow graphs for Antibody A in solutions with pH from

4.5 to 8.5

Figure 2 The appearance of visible particles in solutions of Antibody A

(l .Omg/mL) with a pH of 5.5 and 0% and 0.1% polysorbate 80 with shear. The results are the average of 2 experiments.

Figure 3 The appearance of visible particles in solutions of Antibody A

(lOmg/mL) with a pH of 5.5 and 0%, 0.02% and 0.1% polysorbate 80 with shear. The results are the average of at least 4 experiments.

Figure 4 Stability of Antibody A in 2 formulations with pH 5.5 or 6.0

containing 0.05mM EDTA and 0.02% Polysorbate 80 following exposure to approximately 300 Watt-hours/m2 for 2, 4, 5 or 6 hours. Assay SEC-HPLC.

Detailed Description

As used herein, "about" as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or ±10%), including ±5%, ±1%, and ±0.1%> from the specified value, as such variations are appropriate to perform the disclosed methods.

The optimal embodiment of this invention was determined after significant screening studies and is a formula containing 50mg/mL of Antibody A in a solution containing 50mM sodium acetate, 0.02% polysorbate 80, 1%> arginine, 51mM sodium chloride, at pH 5.5.

One such screening study involved subjecting Antibody A to various ranges of pH while otherwise maintaining a constant buffer formulation. The pH range investigated during this study was from pH 4.5 to pH 8.5 at 0.5 pH unit intervals. Assays such as ELISA, RP-HPLC, and SEC-HPLC were used to determine the stability profile of the samples.

Results from the pH investigation show that all assays agreed that the stability of Antibody A at 50°C is poor at pH 4.5, pH 8.0 and pH 8.5. The ELISA results indicated that the highest activity was maintained following storage at 50°C for 3 weeks at pH ranging from 5.0 to 6.0. The ELISA data also indicate that Antibody A has a poor thermal stability. The RP-HPLC results suggested that the stability of Antibody A was highest in solutions with a pH ranging from pH 5.5 to 6.0. The SEC- HPLC results indicated an increase in low molecular weight fractions (LMWF) in solutions with pH ranging from 7.5 and 8.5 and that the lowest %> of aggregates was produced in solutions with pH = 5.5 to 7.0. The pH stability study indicated that the optimum stability for Antibody A in solution will be obtained at pH= 5.5 to 6.0. Table 1. Analytical results (ELISA, SEC-HPLC and RP-HPLC) for pH stability study for Antibody A following 3 weeks storage at 50°C and 5°C (ELISA and RP-HPLC only).

Further investigation of the pH stability of the formulation focused on the most stable range indicated by Table 1 (pH 5.5, 6.0, and 6.5) and the addition of 1% arginine and polysorbate 80 (PS80). The samples were analysed by ELISA, SEC-HPLC and c-IEF. Tables 2-4 show the analytical results from storing the solutions for 1, 2 and 3 week at 40°C and 5°C.

Table 2. c-IEF results for pH stability study for Antibody A following 1, 2 and

3 weeks storage at 40°C and 5°C

Method c-IEF

Samples 5°C 40°C

1 week 2 3 weeks lweek 2 weeks 3 weeks weeks

pH 5.5 8.42, 58.7 NT NT 8.47, 8.52, 31.9** 8.52, 23.6**

8.28, 29.6 50.2 8.40, 37.5 8.38, 34.2

8.1, 11.6 8.33, 8.28, 18.2 8.28, 24.5

35.1 8.18, 12.4 8.19, 17.8

8.18,

14.8 pH 5.5 +PS 8.5, 54.3 NT NT 8.47, 8.61, 34.0** 8.52, 22.4**

8.36, 29.4 43.4 8.47, 35.9 8.4, 34.6

8.22, 16.3 8.34, 8.39, 22.2 8.27, 31.1

31.5 8.29, 7.9 8.16, 11.9

8.19,

25.1 pH 8.46, 52.4 NT NT 8.46, 8.50, 38.3** 8.49, 22.2**

5.5+PS+Arg 8.33, 30.7 46.7 8.43, 34.8 8.38, 35.4

8.19, 16.9 8.33, 8.19, 17.9 8.25, 28.4

35.9 8.18, 9.0 8.13, 14.0

8.17,

17.5 pH 6.0 8.51, 49.3 NT NT 8.47, 8.51, 23.8 8.50, 15.5**

8.38, 30.3 45.2 ** 8.36, 8.39, 41.7

8.26, 20.4 8.34, 32.2 8.17, 8.25, 24.7

35.9 28.5 8.15, 8.05, 18.1

8.19, 15.5

18.9 pH 6.0 + PS 8.45, 57.9 NT NT 8.40, 8.49, 17.0** 8.50, 13.7**

8.34, 30.7 46.3 * 8.38, 28.0 8.38, 36.4

8.20, 11.4 8.26, 8.27, 36.3 8.25, 37.5

40.3 8.02, 18.7 8.14, 12.4

8.09,

13.4 pH 6.0 + PS 8.53, 51.8 NT NT 8.53, 8.49, 27.6** 8.50, 17.9**

+ Arg 8.39, 28.4 46.8* 8.38, 36.9 8.38, 30.9

8.28, 19.9 8.39, 8.19, 28.0 8.26, 24.1

38.2 8.17, 7.5 8.03, 27.2

8.26,

15.0 pH 6.5 + PS 8.54, 54.7 NT NT 8.56, 8.51, 15.1 ** 8.39, 26.0**

+ Arg 8.40, 31.2 33.7** 8.39, 30.1 8.29, 30.7

8.29, 14.2 8.44, 8.28, 27.7 8.15, 24.1

38.6 8.05, 27.2 7.79, 19.2

8.31,

27.8

PS = 0.02% Polysorbate 80

Arg = 1% Arginine

NT = not tested

* Conforms to interim reference with minor variations

** Significant changes compared to interim reference

The c-IEF results (Table 2) suggested that Antibody A is most stable in a solution with pH 5.5. The addition of Polysorbate 80 generally reduced the heat stability of the molecule. Arginine appeared to have little or no stabilising effect on the heat stability of Antiobody A.

Table 3. SEC-HPLC results for pH stability study for Antibody A with and

without Polysorbate 80 and arginine following 1, 2 and 3 weeks storage at 40°C

Method SEC-HPLC, 40°C

Samples 1 week 2 weeks 3 weeks

Mono Agg LMWF Mono Agg LMWF Mono Agg LMWF pH 5.5 98.5 1.4 0.1 98.1 1.6 0.3 97.4 2.1 0.6 pH 5.5 +PS 98.4 1.5 0.1 97.6 2.1 0.3 96.7 2.8 0.6 pH 98.7 1.3 0.0 97.4 2.3 0.4 96.5 2.9 0.6

5.5+PS+Arg

pH 6.0 98.3 1.6 0.1 97.6 2.1 0.3 97.1 2.4 0.6 pH 6.0 + PS 98.1 1.8 0.1 97.4 2.4 0.3 96.2 3.2 0.6 pH 6.0 +PS 98.2 1.7 0.1 96.8 2.9 0.3 95.3 4.1 0.6 +Arg pH 6.5 96.5 3.3 0.2 95.9 3.8 0.4 95.2 4.2 0.6

0.02% Polysorbate 80

= 1% Arginine

The SEC-HPLC results (Table 3) also indicated that Antibody A was most stable in a solution with a pH of 5.5 and that the presence of Polysorbate 80 in the solution reduced the heat stability of the active.

ELISA results for pH stability study for Antibody A (pH 5.5, 6.0,and 6.5) with and without polysorbate 80 (0.02%) and arginine (1%) following 2 and 3 weeks storage at 40°C.

PS = 0.02% Polysorbate 80

Arg = 1% Arginine

*The initial concentration of anti-P-amyloid antibody was 62.3mg/mL

** Concentration calculated to indicate activity for an initial concentration of

Thermal stability of various formulation was investigated by the use of DSC over a range of pH values from pH 4.5 to pH 8.5 at 0.5 pH unit intervals. Table 5 lists the average thermal events for each sample and Figure 1 shows representative results. All the data suggest that the thermal stability for Antibody A is good irrespective of pH. Onset of denaturation ranged from 60.4°C to 72.0°C and precipitation (peak top) from approximately 70.4°C to 81.7°C. This event is further illustrated in Figure 1.

Table 5. Thermal events for Antibody A in solutions with pH from 4.5 to 8.5

(average of 2 results)

A further investigation of the formulation was to determine the shear stability of anti- β-amyloid antibody in the presence and absence of Polysorbate 80. Antibody A was diluted to lmg/ml and lOmg/ml with acetate buffer pH 5.5 and spiked with

polysorbate 80 to achieve a concentration of 0.0%, 0.02% or 0.1% (w/v) in the samples for testing. A 2mL sample of each solution was filtered through a 0.2μπι filter and added to a luminescence cuvette with a stirring flea. The cuvette was placed in a Perkin Elmer LS 50B fluorimeter thermostatted to 20°C and with stirring on high speed. A measure of the quantity of visible particulates in the stirred cuvette was obtained from luminescence measurements with the excitation and emission wavelength set to 400nm. Analysis of the stirred sample was carried out every 30 minutes. Each study was continued for 360 minutes. The luminescence with time for solutions with Antibody A concentration of l .Omg/ml with and without Polysorbate 80 is shown in Figure 2. The results are the average of 2 runs. The results for lOmg/ml solutions of Antibody A with and without Polysorbate 80 are shown in Figure 3. These results are the average of at least 4 runs. The Figures suggests that Antibody A is sensitive to shear in a solution with pH 5.5. The addition of 0.1% and 0.02% polysorbate 80 significantly reduced the sensitivity to shear.

In yet another formulation investigation, the effect of ethylenediaminetetraacetic acid (EDTA) as a chelator in the presence and absence of CU(II) was studied.

Table 6. Stability of 20mg/mL Antibody A in solutions with pH 5.5 and 6.0 with and without Cu(II) and EDTA measured by SEC-HPLC and ELISA

Assay SEC-HPLC ELISA

Sample monomer Aggregate LMWF Activity

(mg/mL) pH5.5 99.2 0.8 0.0 18.5 pH 5.5 +EDTA 99.0 1.0 0.0 17.9 pH 99.1 0.9 0.0 18.6

5.5+EDTA+luLCu

pH 99.1 0.9 0.0 21.6

5.5+EDTA+5uLCu

pH 99.2 0.8 0.0 19.2

5.5+EDTA+lOuLCu

pH 5.5+ Cu luL 98.4 1.1 0.5 20.0 pH 6.0 99.2 0.8 0.0 15.1 pH 6.0 + EDTA 99.3 0.7 0.0 20.0 pH 6.0 + EDTA + 99.3 0.7 0.0 21.8 luL Cu

pH 6.0 + EDTA+ 99.3 0.7 0.0 19.9

5uL Cu

pH 6.0 + EDTA+ 99.3 0.7 0.0 23.7 lOuL

pH 6.0 +Cu luL 98.9 0.8 0.3 16.6 The results from the SEC-HPLC and ELISA analysis are shown in Table 6. No conclusions could be made from the ELISA results except that activity was unaffected by addition of EDTA. The SEC-HPLC results suggested that when 0.05 mM EDTA had been added to the solution, the stability of Antibody A was unaffected. The addition of Cu(II) to the anti-P-amyloid antibody solution caused degradation of Antibody A. The addition of EDTA and Cu(II) to the solution of active reduced the degradation compared to the sample without EDTA.

Yet further investigations revealed the susceptibility of Antibody A to degradation when subjected to specified light intensities for various lengths of time.

Table 7. Stability of Antibody A following exposure to approximately 300

Watt-hours/m2 for 2, 4, 5 or 6 hours. Assay SEC-HPLC.

The results from the light study are shown in Table 7 and a graphical representation is given in Figure 4. The Table and Figure show an increase in the amount of aggregates on exposure to light. The increase in aggregates with time suggested that the product should be protected from light. In yet a further investigation, a concentration range Antibody A from 50mg/mL to 150mg/mL was tested over 12 weeks at various storage temperatures. The samples were subjected to a similar battery of stability indicating tests (SEC-HPLC, cIEF, etc.) as were preformed on in both the thermal and pH investigations. Assay results from the study showed little to no difference in the stability at either of the concentration.

SEQUENCE LISTING

Heavy chain V region of Antibody A (SEQ ID No:7)

EVQLVESGGGLVQPGGSLRLSCAVSGFTFSDNGMAWVRQAPGKGLEWVSFISNL AYS I D YA DT VTG RFTISRDNAKNSLYLQMNSLRAE DTA VYYC VSGT WF AY WG QGT L VTVSS

Light chain V region of Antibody A (SEQ ID No:8)

DIVMTQSPLSLPVTPGEPASISCRVSQSLLHSNGYTYLHWYLQKPGQSPQLLIYKVS NRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQTRHVPYTFGGGTKVEIK Heavy chain amino acid sequence of Antibody A (SEQ ID No:9)

EVQLVESGGGLVQPGGSLRLSCAVSGFTFSDNGMAWVRQAPGKGLEWVSFISNL AYS I D YA DT VTG RFTISRDNAKNSLYLQMNSLRAE DTA VYYC VSGT WF AY WG QGT L VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVH TFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT CPPCPAPELAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Light chain amino acid sequence of Antibody A (SEQ ID No:10)

DIVMTQSPLSLPVTPGEPASISCRVSQSLLHSNGYTYLHWYLQKPGQSPQLLIYKVS NRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQTRHVPYTFGGGTKVEIKR TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVT EQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

Claims

1. An anti-β -amyloid antibody pharmaceutical formulation comprising a

therapeutically effective amount of an anti-P-amyloid antibody, wherein the formulation further comprises 10 to 100 mM sodium acetate, 25 to 100 mM sodium chloride, 0.5 to 5% arginine free base, 0.02 to 0.2 mM EDTA, 0.01 to 0.2 w/v % polysorbate 80 and adjusted to pH 5.0 to 7.0.

2. The anti-P-amyloid antibody pharmaceutical formulation of Claim 1, wherein the anti-P-amyloid antibody is an antibody having variable heavy and variable light regions comprising the following CDRs:

CDRH1 : DNGMA (SEQ ID No: 1)

CDRH2: FISNLAYSIDYADTVTG (SEQ ID No:2)

CDRH3 : GTWFAY (SEQ ID No:3)

within the variable heavy region, and;

CDRL1 : RVSQSLLHSNGYTYLH (SEQ ID No:4)

CDRL2: KVSNRFS (SEQ ID No:5)

CDRL3 : SQTRHVPYT (SEQ ID No:6)

within the variable light chain region.

3. The anti-P-amyloid antibody pharmaceutical formulation of Claim 2, wherein the anti-P-amyloid antibody is an antibody having a heavy chain variable region having the sequence set forth in SEQ ID No:7, and a light chain variable region having the sequence set forth in SEQ ID No: 8.

4. The anti-P-amyloid antibody pharmaceutical formulation of Claim 2, wherein the anti-P-amyloid antibody is an antibody having the heavy chain having the sequence set forth in SEQ ID No: 9, and a light chain having the sequence set forth in SEQ ID No: 10.

5. The anti-β -amyloid antibody formulation of Claim 2, wherein the anti-P-amyloid antibody is present in an amount of about 20-300 mg/mL.

6. The anti-β -amyloid antibody formulation of Claim 2, wherein the sodium acetate is present in an amount of about 50mM.

7. The anti-P-amyloid antibody formulation of Claim 2, where in the pH is about 5.5.

8. The anti-P-amyloid antibody formulation of Claim 2, wherein the sodium chloride is present in an amount of about 51 mM.

9. The anti-P-amyloid antibody formulation of Claim 2, wherein the arginine free base is present in an amount of about 1%.

10. The anti-P-amyloid antibody formulation of Claim 2, wherein the EDTA is present in an amount of about 0.05 mM.

11. The anti-P-amyloid antibody formulation of Claim 2, wherein the polysorbate 80 is present in an amount of about 0.02%.

12. The anti-P-amyloid antibody formulation of Claim 2, where in the anti-P-amyloid antibody is present in about 50 mg/mL, and wherein the formulation further comprises 50 mM sodium acetate, 51 mM sodium chloride, 1% arginine free base, 0.05 mM EDTA, 0.02% polysorbate 80, and adjusted to pH 5.5.

13. The anti-P-amyloid antibody pharmaceutical formulation of Claim 2 which is thermostable.

14. The anti-P-amyloid antibody pharmaceutical formulation of Claim 2 which is shear stable.

15. The anti-P-amyloid antibody pharmaceutical formulation of Claim 2 for subcutaneous or intramuscular administration.

16. A kit comprising one or more vials containing the the anti-β -amyloid antibody pharmaceutical formulation of Claim 2 and instructions for subcutaneous or intramuscular administration of the formulation to a patient.

17. A method of treating a human patient afflicted with a disease or disorder effecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits which comprises administering an anti-P-amyloid antibody formulation of Claim 2.

18. A method of treating a human patient afflicted with a disease or disorder effecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits of Claim 13 in which the disease or disorder is age-related macular degeneration (AMD) glaucoma or β-amyloid dependent cataract formation.

19. A method of treating AMD of claim 14 in which AMD is geographic atrophy.

20. The method of claim 13 or 14 in which the formulation is further delivered via subcutaneous or intramuscularly.

21. The pharmaceutical formulation according to any preceding claims for use in therapy.

22. The pharmaceutical formulation according to any preceding claims for the treatment of a disease or disorder amenable to treatment with an anti^-amyloid antibody.

23. The formulation according to any preceding claims for use in the treatment of disease or disorder effecting the eye or optic nerve characterized by elevated β- amyloid levels or β-amyloid deposits.

24. The formulation according to the preceding claim in which the disease or disorder is age-related macular degeneration (AMD), geographic atrophy, glaucoma or β- amyloid dependent cataract formation.

25. Use of a formulation according to any preceding claim in the manufacture of a medicament for use in the treatment of a disease or disorder effecting the eye or optic nerve characterized by elevated β-amyloid levels or β-amyloid deposits.

26. Use of a formulation according to the preceding claim in which the disease or disorder is age-related macular degeneration (AMD), geographic atrophy, glaucoma or β-amyloid dependent cataract formation.