Genentech, Inc.
[2010] APO 27
•15 November 2010
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Genentech, Inc. [2010] APO 27
Patent Application: 2007200135
Title:Treatment with anti-ErbB2 antibodies
Patent Applicant: Genentech, Inc.
Delegate: Dr S.D.Barker
Decision Date: 12 November 2010
Hearing Date: 15 October 2010, in Canberra
Catchwords: PATENTS – examiner's objection – method of treating tumor – whether an inventive step – citations disclose xenograft models – whether it would have been a matter of routine to proceed to treatment of human patients – all claims lack inventive step – application refused
Representation: Patent applicant: Amanda Stark of Griffith Hack
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2007200135
Title:Treatment with anti-ErbB2 antibodies
Patent Applicant: Genentech, Inc.
Date of Decision: 12 November 2010
DECISION
I refuse the application.
REASONS FOR DECISION
Patent application 2007200135 was filed by Genentech, Inc. on 12 January 2007. The application is a divisional application of patent application 2002301764, which in turn was a divisional application of patent application 19081/99. The earliest priority date is 12 December 1997. Each of the earlier applications lapsed for failure to gain acceptance within the prescribed period.
Three adverse reports issued in relation to the present application. The outstanding issue is lack of inventive step, and equivalent objections were taken against the parent and grandparent applications. Consequently the applicant was offered a hearing to deal with the outstanding objections. The hearing was held in Canberra on 15 October 2010. The applicant was represented by Amanda Stark, patent attorney of Griffith Hack.
The applicant filed a divisional application (number 2010235842) on 14 October 2010, i.e. the day before the hearing of the present matter.
Background
The invention lies in the area of pharmaceutical chemistry, particularly the treatment of certain cancers. The development of new treatments involves a series of clinical trials through several phases.
Phase 1 trials assess whether an experimental medication or treatment is safe, and gather information on how the active agents are absorbed, metabolised, etc..
Phase 2 trials are done to assess the short term therapeutic effect of the medication or treatment.
Phase 3 trials are done on a large number of patients over a prolonged period, to demonstrate advantages over other therapies.Successful outcomes in one phase are a prerequisite before advancing to the next phase.
The following is a brief explanation of some of the technical terminology used in the specification and in the citation.
Cell membrane receptor A protein embedded in the outer membrane of a cell. The portion of the protein outside of the cell is the extracellular domain. The binding of a ligand to the receptor causes a response in the cell. ErbB2 A cell membrane receptor; also known as HER2 HER2 See ErbB2 Paclitaxel An anti-cancer compound isolated from the bark of the yew tree; TAXOL® is a commercial paclitaxel product Taxoid A class of compounds having a structure similar to that of paclitaxel; known members of the class include paclitaxel and docetaxel 4D5 An epitope (or section of the protein) within the extracellular domain of the ErbB2 receptor MoAb 4D5 A monoclonal antibody against ErbB2 that binds to epitope 4D5 rhuMoAb HER2 A humanised monoclonal antibody that targets the 4D5 epitope of HER2, i.e. a humanised version of MoAb 45 Trastuzumab A humanised monoclonal antibody that targets the 4D5 epitope of HER2; marketed as HERCEPTIN® ATCC CRL 10463 The deposit number of a hybridoma cell line that produces antibody that bind to the 4D5 extracellular domain of the HER2 receptor Xenograft Cells transplanted from one species into another Anthracyclines A class of anticancer drugs derived from Streptomyces bacteria; known members of the class include doxorubicin and epirubicin The specification
It is known that the ErbB2 gene encodes for a glycoprotein receptor which is overexpressed in about 25- 30% of human breast cancers. Antibodies directed to ErbB2 proteins have been found to have anti-tumour effects in a number of studies.
The summary of the invention states:
"the invention concerns a method for the treatment of a human patient susceptible to or diagnosed with a disorder characterised by overexpression of ErbB2 receptor comprising administering a therapeutically effective amount of a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline derivative, e.g. doxorubicin or epirubicin, in the absence of an anthracycline derivative or cisplatin, to the human patient."
The chemotherapeutic agent preferably is a taxoid, such as paclitaxel or a derivative thereof.
The specification as proposed to be amended ends with 26 claims (reproduced in full in the Annex at the end of this decision). Claims 1 and 13 are independent claims. These claims as most recently proposed to be amended are as follows.
1. A method for the treatment of a human patient diagnosed with a malignant progressing tumor or cancer characterised by overexpression of ErbB2 receptor, the method comprising administering to the patient a clinically effective amount of a combination of an intact humanized anti-ErbB2 antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence and a taxoid, wherein the combination when administered has clinical efficacy as measured by determining time to disease progression.
13. Use of an intact humanized anti-ErbB2 antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence in the preparation of a medicament for treatment of a malignant progressing tumor or cancer characterised by overexpression of ErbB2 receptor in a human patient, wherein the medicament is for combined administration of the antibody with a taxoid wherein the combined administration has clinical efficiency as measured by determining time to disease progression.
The construction of these claims is unexceptional. Claim 1 relates to a method of treatment characterised by administering a combination of the specified antibody and a taxoid. The treatment must achieve an improvement in the time to disease progression. Claim 13 is essentially a Swiss style claim, which relates to the "use of" the specified antibody in the preparation of a medicament. The medicament must be suitable for treatment that is essentially that of claim 1. Claim 13 is essentially a method of preparing a medicament which is suitable for use in the treatment of claim 1.
I understand the reference to the "combination" of agents means that the agents can be administered together or sequentially. This is confirmed by claims 2 – 4.
In passing I also note that claim 21 is appended to itself. However, this does not render the claims unclear, and no issues relevant to this decision flow from it. Claim 23 is appended to claim 22, but by analogy with claim 11 it should probably be appended to claim 21.
The objection
The examiner has objected that claims 1 – 26 lack inventive step in the light of the following documents:
D1: Baselga et al, Oncology, vol. 11 (1997) no. 3, supp. 2, pp 43-48
D2: Mendelsohn et al, Annals of Oncology, vol. 7 (1996) supp. 5, p 2, abstract 040
D3: Baselga et al, Annals of Oncology, vol. 5 (1994) supp. 5, p A010
D4: Baselga et al, Proceedings of ASCO, vol. 13 (1994), abstract 53Relevant portions of the examiner's most recent objection are as follows:
"The problem addressed by the current application is the provision of a method of treatment of human patients diagnosed with a malignant progressing tumour or cancer characterised by the overexpression of ErbB2 receptor.
The cited art is directed to a problem similar to the applicant's problem, and in searching the problem a person skilled as identified above could reasonably be expected to have found, and to have ascertained, understood, and regarded, this prior art as relevant.
D1 discloses a method of treating cancer, particularly metastatic breast cancer, through the combined administration of a humanised antibody against ErbB2 and the chemotherapeutic Paclitaxel (a taxoid) (page 45 column 3 lines 3-12, page 46 column 3 lines 12-44). D1 discloses that the humanised antibody against ErbB2 binds to epitope 4D5 within the ErbB2 extracellular domain sequence (MoAb 4D5) (page 44 column 1 lines 27-46). D1 discloses preclinical studies of the MoAb 4D5 in combination with paclitaxel in monolayer cell culture soft agar and breast cancer human tumor xenografts in nude mice with the disappearance of well-established xenografts (page 45 column 3 lines 12-44). D1 further discloses the combination of MoAb 4D5 with paclitaxel resulted in 93% inhibition of tumour growth on the nude mice xenograft model. This combination demonstrated a synergistic effect compared to MoAb or paclitaxel when administered alone in the in vivo study. Similarly D2 – D4 all disclose that the combination of a 4D5 antibody and a taxoid in the nude mice xenograft model displayed a synergistic effect. …
As noted by the applicant D1-D4 differ from the presently claimed invention in that they disclose the use of an anti-ErbB2 antibody and a taxoid against xenografts of human breast cancer in nude mice models, rather than the direct treatment of human patients. The applicant has stated that xenograft tumor models have only a moderate predictive value for real life clinical situations. The applicant has submitted that therefore the outcome of treatment of human patients with MoAb and taxoid would have been highly unpredictable and that there would be no reasonable expectation of success in following the cited documents.
D1 discloses the design of a phase III multinational clinical study, following the positive results obtained from the xenograft nude mice models that displayed a synergistic effect obtained from the combination of 4D5 antibody and paclitaxel."
Inventive step
According to s 7(2), an invention is taken to involve an inventive step, when compared with the prior art base, unless the invention would have been obvious to a person skilled in the art in the light of the common general knowledge. It is well established that the obviousness question can be formulated as follows:
"The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not."
Wellcome Foundation Ltd v VR Laboratories (Aust) Pty Ltd (1981) 148 CLR 262 at 286 (Aickin J)Recently, the High Court in Aktiebolaget Hassle v Alpharpharm Pty Ltd (2002) 212 CLR 411 at 433 [53] stated that it is also permissible to use the "Cripps question":
Would the notional research group at the relevant date, in all the circumstances, which include a knowledge of all the relevant prior art and the facts, directly be led as a matter of course to try the invention as claimed in the expectation that it might well produce a solution to the problem
It is clear that any potential solution to a problem will not be obvious unless it would have been a matter of routine to try that solution, but with the significant caveat that there must be an expectation that the potential solution "might well" solve the problem. It is not necessary that success is guaranteed.
The standard of proof that applies to inventive step objections is addressed in s 49(1):
Subject to section 50, the Commissioner must accept a patent request and complete specification relating to an application for a standard patent, if:
(a) the Commissioner is satisfied that the invention, so far as claimed, satisfies the criteria mentioned in paragraph 18(1)(b);
This provision reflects an amendment in 2001 to insert a "balance of probabilities" test. The Explanatory Memorandum, Patents Amendment Bill (2001) relevantly states:
"This item amends subsection 49(1) of the Patents Act to raise the threshold of the test the Commissioner must apply when assessing an invention against the criteria of paragraph 18(1)(b) of the Patents Act (novelty and inventive step). The amendment replaces the existing 'benefit of doubt' test with a more stringent test for the Commissioner to apply when assessing an invention against these criteria. The benefit of any doubt will continue to apply to the other matters the Commissioner considers under this subsection, but in making a decision as to whether an application meets the requirements of novelty and inventive step, the Commissioner must now be satisfied that there are no lawful grounds of objection."
The standard of proof that applies to inventive step objections is the balance of probabilities.
D1: Baselga J, et al: HER2 Overexpression and Paclitaxel Sensitivity in Breast Cancer: Therapeutic Implications, Oncology vol 11, no 3, supp 2, pp 43 -48, 1997
The examiner's objection is based on four citations. At the hearing I agreed that D1 is the key document. If the applicant can avoid D1, then they will also avoid the other citations.
D1 discloses that overexpression of the HER2 gene plays a significant role in breast cancer pathogenesis. Preclinical models are tested with a range of agents that interfere with HER2 function alone or in combination with conventional chemotherapeutic agents, including paclitaxel.
The most potent anti-HER2 antibody is reported to be the MoAb 4D5 antibody: "Thus, MoAb 4D5 appears to have potential therapeutic applications for tumours overexpressing p185HER2." The citation then refers to a humanised version of the 4D5 antibody denoted rhoMoAb HER2 that had been developed by Genentech. Phase 1 and 2 studies of this antibody are reported, with the finding that it "is clinically active in patients who have metastatic breast cancers that overexpress HER2 and have received extensive prior therapy. A confirmatory study that will include 200 patients with less heavily pretreated metastatic disease is currently underway".
The citation then goes on to discuss the use of the Genentech rhuMoAb HER2 in combination with other chemotherapeutic agents. The tests are conducted in monolayer cell culture soft agar as well as breast cancer human tumor xenografts in nude mice. Paclitaxel plus rhuMoAb HER2 is reported to achieve markedly better results than a combination of doxorubicin and rhuMoAb HER2. Phase 2 trials of rhuMoAb HER2 plus cisplatin showed that the synergy observed for this combination in the laboratory was reproducible in the clinic. The citation then states that the promising results of the phase II studies and the xenograft experiments have led to the design of a phase III multinational study of chemotherapy in combination with rhuMoAb HER2. Patients in the study will receive
"one of two chemotherapy regimens for a minimum of six cycles: cyclophosphamide and doxorubicin or epirubicin, if patients have not received anthracycline therapy in the adjuvant setting; or paclitaxel, if patients have received anthracycline therapy in the adjuvant setting … the main goal of this study is to determine whether the addition of this anti-HER2 antibody increases the time to disease progression compared with the group of patients treated with antibody alone."
The citation concludes with the statement
"The predictive value of HER2 overexpression for paclitaxel response requires independent confirmation in advanced disease and early breast cancer. This question could be addressed in ongoing studies of paclitaxel-based adjuvant therapy in breast cancer. In preclinical models, the combined therapy of breast cancer cells that overexpress HER2 with agents that interfere with HER2 function and paclitaxel results in a marked antitumor effect. One such strategy, the combination of anti-HER2 MoAb with paclitaxel, is currently being evaluated. If the results of these studies are positive, we might be faced with a novel paradox, in which expression of a receptor that confers a worse prognosis provides us with an opportunity for increased response to taxanes."
It is clear that the citation discloses that rhuMoAb HER2 in combination with paclitaxel inhibits breast cancer tumor growth in xenograft models. The authors state that they are planning to progress to phase 3 trials of this combination (amongst others) in humans.
Is there an inventive step in the light of D1?
Claim 1 and claim 13: It is not in dispute that the problem addressed by these claims lies in the identification of a cancer treatment having improved time to progression (TTP), and that D1 would have been ascertained, understood and regarded as relevant to this problem. The disclosure of D1 is quite clear – it teaches that a combination of rhuMoAb HER2 and paclitaxel shows promising activity in xenograft tests, and the authors are preparing for phase 3 clinical trials.
The key question is whether it would have been a matter of routine to try rhuMoAb HER2 and paclitaxel, which would necessarily involve carrying out phase 3 clinical trials. The citation provides a clear motivation to proceed to phase 3 clinical trials, in line with routine practice. This teaching must be balanced against any reasonable contra‑indications.
Dr Sliwkowski refers to a number of matters, including the unpredictability of outcomes based on xenograft models, and asserts that it would not have been routine to proceed to phase 3 trials. This seems inconsistent with other evidence presented by the applicant. The article in Clinical Cancer Research (2003) 9, 4227 – 4239 (published after the priority date of the present application, but provided by the applicant to establish the state of knowledge in relation to xenografts in 1997) states
"Both basic science studies and clinical trials are essential components of the cancer drug discovery process. Potential therapeutics found to be significantly better than no treatment or standard therapies (i.e. active) in preclinical laboratory cancer models or compounds with novel chemotypes and equivalent effectiveness to standard treatments are advanced to confirmatory testing in early (Phase I and II) clinical trials. Considering that RR [response rate] is a reasonable surrogate end point for survival (required but not sufficient), a favourable RR in Phase II trials advances a drug into additional clinical testing and is considered a prerequisite of drug success in the clinic."
It seems clear that phase 2 trials are an essential prerequisite to phase 3 trials, and it is routine to proceed to phase 3 if phase 2 has been successful. Dr Sliwkowski appears to agree at paragraph 10 of his second declaration:
"while tumor xenograft models are useful and necessary tools to develop and expand treatment options for various types of human cancer, they are by no means sufficient to predict whether such treatments would work in a human clinical setting, and, in particular, whether a clinical endpoint, such as increase in time to disease progression, could be achieved."
Dr Sliwkowski's point seems to be that success in phase 3 is not guaranteed, which is clearly correct. However, Dr Sliwkowski seems to equate matters of routine, reasonable expectations of success and guarantee of success. That is not the approach endorsed by the Alphapharm case. The proper question is whether there would have been an "expectation that it might well" be successful. Consequently I have come to a different conclusion to Dr Sliwkowski, and I am satisfied that it would have been a matter of routine in the art to advance to phase 3 as indicated in D1. It also follows that I believe there would have been a reasonable expectation of success (while accepting that success was not guaranteed). Consequently, claims 1 and 13 lack inventive step.
D1 also teaches that other drug combinations have been tested in xenograft models, and that cyclophosphamide and doxorubicin or epirubicin in combination with rhuMoAb HER2 will be tested in the clinical trial. It is not necessary to establish that only ONE course of action would have been a matter routine; it must be established that the course of action that is now claimed would have been a matter of routine. In the present case I am satisfied that there would have been a reasonable expectation that the combination of rhuMoAb HER2 and paclitaxel would work. Looked at in a different way, the present applicant seems to have verified the prediction of the citation. Mere verification is not invention.
The appended claims: Turning now to the appended claims, they refer to the order of administration of the substances, details of the antibody, detail of the taxoid, and details of the cancer. While these claims were not discussed at the hearing, it is clear that most of these details are explicitly disclosed in D1.
Additional features COMMENTS Claim 2 Administered together D1 reports use "in combination with" Claim 3 Administered separately D1 reports use "in combination with" Claim 4, 16 Administered consecutively D1 reports use "in combination with" Claim 5, 17 Antibody comprises human immunoglobulin Fc rhuMoAb HER2 is disclosed in D1 Claim 6, 18 Antibody binds to the sequence in SEQ ID NO 9, i.e. the 4D5 epitope rhuMoAb HER2 is disclosed in D1 Claim 7, 19 Antibody is obtained from ATCC CRL 10463 rhuMoAb HER2 is disclosed in D1 Claim 8, 20 Taxoid is paclitaxel or docetaxel Paclitaxel is disclosed in D1 Claim 9, 22 Effective amount of antibody and taxoid administered together is less than the sum of the effective amount when administered separately Synergy is indicated in D1 Claim 10, 21 Cancer is selected from group including breast cancer Breast cancer is specifically mentioned in D1 Claim 11, 23 Cancer is breast cancer Specifically mentioned in D1 Claim 12, 24 Cancer is metastatic breast cancer Specifically mentioned in D1 Claim 14 Antibody and taxoid administered together in the absence of an anthracycline D1 discloses treatment without anthracycline Claim 15 Medicament contains separate antibody and taxoid, in the absence of an anthracycline D1 discloses treatment without anthracycline
When addressing whether there is an inventive step in an appended claim, it is necessary to determine the problem solved by that claim. In the present case I see no need to vary the problem except in relation to claims 10 – 12 and 21, 23, 24. Here the problem should be seen as a treatment of the specific cancers listed in those claims.
It is clear that D1 discloses most of the additional features that are added by the appended claims. In the case of claims 2, 3, 4 and 16, I cannot see that a combined or separate administration is anything other than a matter of routine or optimisation. In relation to claims 6 and 18 rhuMoAb HER2 binds to the 4D5 epitope. In relation to claims 5, 7, 17 and 19, it is uncertain whether rhuMoAb HER2 meets the qualifications of these claims. However, on the assumption that it does not, the use of an equivalent antibody appears merely a matter of routine. I have no doubt that the appended claims 2 – 12 and 14 – 24 also lack inventive step.
The omnibus claims: Claims 25 and 26 are omnibus claims. They are directed to a method of treatment (claim 25) and the use of an antibody in the preparation of a medicament (claim 26).
The method of treatment described in the Example is as follows:
"The patients received one of two chemotherapy regiments for a minimum of six cycles, provided their disease was not progressing … paclitaxel (T, TAXOL®), if patients have received any anthracycline therapy in the adjuvant setting. The initial dose of the HERCEPTIN® antibody preceded the first cycle of either chemotherapy regimen by 24 hours. Subsequent doses of the antibody preceded the first cycle of either chemotherapy administration, if the initial does of the antibody was well tolerated. … Paclitaxel (TAXOL®) was given at a dose of 175 mg/m2 over 3 hours by intravenous administration. All patients receiving paclitaxel were premedicated with dexamethasone (or its equivalent) 20 mg x 2, administered orally 12 and 6 hours prior to paclitaxel; diphenhydramine (or its equivalent) 50 mg, iv, administered 30 minutes prior to paclitaxel, and dimetidine (or another H2 blocker) 300 mg, iv, administered 30 minutes prior to paclitaxel."
The antibody preparation is described in the Example as follows:
"On day 0, a 4 mg/kg dose of humanized anti-ErbB2 antibody (HERCEPTIN®, H) was administered intravenously, over a 90-minute period. Beginning on day 7, patients received weekly administration of 2 mg/kg antibody (i.v.) over a 90 minute period."
It is clear that there is very little detail provided by the Example, and there is nothing to suggest that these are anything other than mere matters of optimisation (which is routine and not inventive). Claims 25 and 26 also lack inventive step.
Conclusion
I am satisfied that all of the claims lack inventive step. Consequently the application should be refused unless there is some valid subject matter that could be made the subject of a claim. I do not believe that I should allow an opportunity to amend merely because there is the chance that there is such subject matter.
Based on my findings above, even the Example of the invention lacks inventive step. Consequently, any amendment would have to exclude the Example (i.e. the applicant would have to claim an invention that is not exemplified). Based on a consideration of the specification, I consider that it is extremely unlikely that there is another invention that is fully described although not exemplified. I can see no realistic prospects of amending the specification to overcome the lack of inventive step. I will refuse the application.
Dr S.D.Barker
Delegate of the Commissioner of PatentsANNEX: The claims as proposed to be amended on 13 October 2010
1. A method for the treatment of a human patient diagnosed with a malignant progressing tumor or cancer characterised by overexpression of ErbB2 receptor, the method comprising administering to the patient a clinically effective amount of a combination of an intact humanized anti-ErbB2 antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence and a taxoid, wherein the combination when administered has clinical efficacy as measured by determining time to disease progression.
2. The method according to claim 1, wherein the antibody and the taxoid are administered together in a single formulation.
3. The method according to claim 1, wherein the antibody and the taxoid are administered separately to the patient.
4. The method according to claim 3, wherein administration of the antibody and the taxoid is consecutive and in either order.
5. The method according to any one of claims 1 to 4, wherein the antibody comprises a human immunoglobulin Fc.
6. The method according to any one of claims 1 to 5, wherein the antibody binds to one or more residues of the sequence set forth in SEQ ID NO. 9.
7. The method according to any one of claims 1 to 6, wherein the antibody is a humanized antibody obtainable from deposit ATCC CRL 10463.
8. The method according to any one of claims 1 to 7, wherein the taxoid is paclitaxel or docetaxel.
9. The method according to claim 2, wherein the effective amount of the antibody and the taxoid administered together in a single formulation is lower than the sum of the effective amounts of the antibody and the taxoid administered separately.
10. The method of any one of claims 1 to 9 wherein said cancer is selected from the group consisting of breast cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial cancer, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
11. The method of claim 10 wherein said cancer is breast cancer.
12. The method of claim 11 wherein said breast cancer is metastatic breast carcinoma.
13. Use of an intact humanized anti-ErbB2 antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence in the preparation of a medicament for treatment of a malignant progressing tumor or cancer characterised by overexpression of ErbB2receptor in a human patient, wherein the medicament is for combined administration of the antibody with a taxoid wherein the combined administration has clinical efficiency as measured by determining time to disease progression.
14. Use according to claim 13 wherein the medicament contains a single formulation of a combination of the antibody and a taxoid, in the absence of an anthracycline derivative.
15. Use according to claim 13 wherein the medicament contains separate formulations of (i) the antibody and (ii) the taxoid, in the absence of an anthracycline derivative.
16. Use according to claim 15 wherein the separate formulations are for consecutive administration in either order.
17. Use according to any one of claims 13 to 16 wherein the antibody comprises a human immunoglobulin Fc.
18. Use according to any one of claims 13 to 17 wherein the antibody binds to one or more residues of the sequence set forth in SEQ ID NO: 9.
19. Use according to any one of claims 13 to 18 wherein the antibody is a humanized antibody obtainable from deposit ATCC CRL 10463.
20. Use according to any one of claims 13 to 19 wherein the taxoid is paclitaxel or docetaxel.
21. Use according to any one of claims 13 to 21 wherein said cancer is selected from the group consisting of breast cancer, squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, colorectal cancer, endometrial cancer, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma and various types of head and neck cancer.
22. Use according to claim 14 wherein the amount of the combination of the antibody and taxoid in the medicament is lower than the sum of the antibody and the taxoid when formulated for individual administration as single agents.
23. Use according to claim 22 wherein said cancer is breast cancer.
24. Use according to claim 23 wherein said breast cancer is metastatic breast carcinoma.
25. A method for the treatment of a malignant progressing tumor or cancer as claimed in claim 1 and substantially as herein described with reference to the Example.
26. Use of an anti-ErbB2 antibody in the preparation of a medicament for treatment of a malignant progressing tumor or cancer as claimed in claim 13 and substantially as herein described with reference to the Example.
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