The University of British Columbia
[2020] APO 15
•20 March 2020
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
The University of British Columbia [2020] APO 15
Patent Application: 2015202689
Title:14-3-3 eta antibodies and uses thereof for the diagnosis and treatment of arthritis
Patent Applicant: The University of British Columbia
Delegate:Dr S.D. Barker – Deputy Commissioner of Patents
Decision Date: 20 March 2020
Hearing Date: Written submissions filed on 28 September 2017
Catchwords: PATENTS – objections under section 40 raised during examination – grounds cannot be maintained – directed to return to examination for consideration of the grounds of novelty and inventive step
Representation: Patent attorney for the applicant: Griffith Hack
IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2015202689
Title:14-3-3 eta antibodies and uses thereof for the diagnosis and treatment of arthritis
Patent Applicant: The University of British Columbia
Date of Decision: 20 March 2020
DECISION
The grounds of objection raised by the examiner cannot be maintained.
The application cannot proceed to acceptance because there has not yet been an examination in relation to novelty and inventive step. I direct that examination of these grounds take place as expeditiously as possible.
REASONS FOR DECISION
The present matter is governed by the Patents Act 1990 as amended by the IP Laws Amendment (Raising the Bar) Act 2012.
At the outset I note that there has been a lengthy period between the applicant requesting a hearing in this matter and the issuing of this decision. I regret the delay and any inconvenience caused by that delay.
Patent application 2015202689 is a divisional of patent 2008329529. The application is presently undergoing examination. A third report issued on 7 September 2017, maintaining the grounds of objection of clear enough and complete enough disclosure, support and best method of performance (section 40(2) and 40(3)). The grounds of novelty and inventive step were reserved pending resolution of the section 40 matters. The applicant asked to be heard in relation to the objections under section 40.
The technology of the application is antibodies. The antibodies have the property that they "specifically bind to the eta isoform of the 14-3-3 protein and are capable of discriminating between the eta isoform and other 14-3-3 protein isoforms".[1] The description (and claims) refer to raising antibodies against antigens having SEQ ID NOs 1-32 as set out in the specification. The antibodies are said to have utility in determining the presence of 14-3-3 eta protein and in the diagnosis of conditions including arthritis. The claims as most recently proposed to be amended are directed to methods of determining the presence of the eta protein in a sample using the antibodies, and kits containing an immobilised antibody.
[1] Specification at page 1.
Section 40(2)(a) – clear enough and complete enough disclosure
Section 40(2)(a) sets out the requirement that a specification must
disclose the invention in a manner which is clear enough and complete enough for the invention to be performed by a person skilled in the relevant art
The Deputy Commission in Evolva SA[2] (Evolva) said of this provision:
"In general, the extent of the disclosure necessary to make the patent sufficient will depend upon the nature of the invention, the scope of the claims and the art in which the invention is made."[3]
[2] [2017] APO 57.
[3] Evolva at [27].
Considerations that are relevant in assessing this provision are:
"EP and UK decisions have provided some general guidance on factors that come into consideration, including: uncertainty and a lack of predictability, incomplete experimental details and a lack of guidance in the specification including instructions on how to proceed in case of failure."[4]
[4] Evolva at [34].
The Deputy Commissioner went on to consider the question of "plausibility" in this assessment:
"the scope of the monopoly, as defined in the claims, must correspond to the technical contribution the patentee has made to the art. If the assertions made in the specification are not plausible then it cannot be reasonably said that the patentee has made a contribution to the art."[5]
and
"an invention that is plausible may still fail on sufficiency if the specification essentially sets out a research programme and there is an undue burden of experimentation required to put it into practice. If an invention is implausible then it would inherently require an undue burden of experimentation to put it into practice (if at all)."[6]
[5] Evolva at [43].
[6] Evolva at [44].
I note that the Evolva decision issued after the applicant filed its written submissions. However, I consider that the Evolva decision sets out a proper understanding of the law, and I will adopt the approach set out by the Deputy Commissioner.
The examiner took the view that there would be an undue burden in preparing antibodies to the various SEQ IDs and assaying them to determine whether they selectively bind to the eta protein.
In response the objection, the applicant has provided a declaration by Dr Anthony Marotta, who is an inventor of the present application. Dr Marotta stated:
"The issue as I understand it is whether the present description provides sufficient guidance for the skilled person to discriminate between hybridomas generating the desired anti eta 14-3-3- antibodies and hybridomas generating undesired non-specific antibodies such as 4F10. I would like to offer the following comments regarding the methods of preparing monospecific anti-14-3-3 eta antibodies described in the Examples section of the present specification, our interpretations thereof, and the understanding in the art by the international scientific community.
As shown in table 4a at page 36, 5 monoclonal antibodies raised using 14-3-3 eta residues 143-157 have been generated. Four of these antibodies, i.e. 2D5, 7F8, 7H8 and 8F10, show specificity for the eta isoform of 14-3-3. In table 4a, this specificity is demonstrated by an ELISA value of more than 0.1 at a 1:15 dilution, i.e. 0.351 for 2D5, 0.946 for 7F8, 0.774 for 7H8 and 0.169 for 8F10 (it is noted that when the 1:30 dilution values are considered the specificity is even more pronounced). In contrast, the ELISA signal for the non-eta isoforms generally is below 0.1. Formulated differently, a clear and discriminative ELISA signal of more than 0.1 is obtained when an antibody according to the present invention specifically recognises the eta 14-3-3 isoform.
The 4F10 antibody referred to by the Examining Division allegedly showing that the 14-3-3 eta residues 143-157 epitope is not capable of raising eta specific antibodies, provides in all cases an ELISA value of below or around 0.1 indicating that this antibody is not capable of recognizing any 14-3-3 protein isoform. Formulated differently, antibody 4F10 appears to be produced by an hybridoma generating a non-specific antibody and the ELISA values of less of around 0.1 presented in table 4a are to be regarded as background levels. This is confirmed in table 4b at page 37 showing the ELISA results corrected for background levels. In table 4b, only specific antibodies 2D5, 7F8, 7H8 and 8F10 yield a signal.
The generation of non-specific hybridomas, the present case the hybridoma generating antibody 4F10, is not to be regarded as a verifiable fact that the epitope used to generate the hybridoma is not specific. In contrast, non-specific hybridomas are commonly generated in any immunization protocol and thus are not regarded by the skilled person as evidence that the epitope is not capable of generating the present inventive and unique eta 14-3-3 specific antibodies. Thus the present description provides sufficient guidance for the skilled person to discriminate between hybridomas generating the desired anti eta 14-3-3- antibodies and hybridomas generating the undesired non-specific antibodies such as 4F10."[7]
[7] Declaration of Anthony Marotta filed 30 August 2017, paragraphs 2 – 5.
I consider that Dr Marotta provides a basis to consider that the specification provides a general method of producing hybridomas, and there is an explanation of how to distinguish hybridomas that produce the desired antibodies. The evidence indicates that the testing is routine in the art and is not onerous. The guidance provided by the specification is a relevant consideration, as indicated in the Evolva decision, and in the absence of a plausible reason to think otherwise it is a decisive consideration in this case. I am not satisfied that there is not a clear enough and complete enough disclosure.
Section 40(3) – support
Section 40(3) sets out the requirement that a specification must
supported by matter disclosed in the specification
In CSR Building Products Limited v United States Gypsum Company[8] (CSR) I stated that the requirement of support means that the claims should correspond to the technical contribution to the art.[9] The presence of a general principle will often be significant:
"An important question will often be whether the technical contribution to the art is a general principle or the specific examples in the specification."[10]
[8] [2015] APO 72.
[9] CSR at [109].
[10] CSR at [113].
The examiner stated that the claims lack support because the body of the specification does not provide sufficient information to enable the skilled addressee to perform the invention over the full scope of the claim. Clearly the examiner saw this ground of objection as linked to the objection under section 40(2)(a), which will often be the case.
The specification indicates that the technical contribution is the production of antibodies selective to the eta isoform by use of select epitopes. The information in the declaration of Dr Marotta supports this conclusion. I consider there is a general principle in the present case, and consequently I am not satisfied that there is a lack of support.
Section 40(2)(aa) – best method of performance
Section 40(2)(aa) sets out the requirement that a specification must
disclose the best method known to the applicant of performing the invention
In Kineta, Inc[11] (Kineta) I said that:
"it is necessary to determine what method is disclosed in the specification, and then to ask whether there is any evidence that the applicant was aware of a better method of performing the invention."[12]
[11] [2017] APO 45.
[12] Kineta at [24].
The examination report asserts that one of the antibodies produced by the hybridomas AUG3-CKNS-2D5, AUG3-CKNS-7F8, AUG3-CKNS-7H8 and AUG4-ETA-8F10 must be the best method known to the applicant, but these antibodies are not described in a way that would enable a person to reproduce them. The examiner suggested that the antibodies could have been described by reciting their complete sequence, 6 CDR sequences or via a deposit under the Budapest Treaty.
Example 1 of the specification states:
"To prepare monospecific anti-14-3-3 eta antibodies, various peptides 8 to 15 amino acids in length, were selected based on our own criteria. These peptides, as well as full-length recombinant native (untagged) 14-3-3 eta were used as immunogens in the production of monoclonal antibodies. A protein sequence alignment for the 7 isoforms of 14-3-3 is shown in Figure 4."
The Example then identifies four immunogens used: C-LDKFLIKNSNDF, KKLEKVKAYR-C, C-KNSVVEASEAAYKEA and full length human recombinant 14-3-3 eta. While the hybridomas produced by the Example do not appear to have been deposited under the Budapest Treaty, I think it is clear what the applicant regards as the best method of producing the hybridomas and the antibodies using the identified immunogens. There is no evidence that the applicant was aware of a better method.
I am not satisfied that the specification does not provide the best method known to the applicant.
Consequences of my decision
The grounds of objection raised by the examiner cannot be maintained. However, the application cannot proceed to acceptance because there has not yet been an examination in relation to novelty and inventive step. I direct that examination of these grounds take place as expeditiously as possible.
Pursuant to regulation 13.4(1)(g), the present application will not lapse until the expiry of the period 3 months from the date of this decision. However, the Commissioner can substitute a period longer than 3 months if satisfied that acceptance should be postponed.[13] I will consider whether to substitute a longer period if the applicant requests, and provides an explanation of why a longer period is appropriate.
[13] Regulation 13.4(3).
Dr S.D. Barker
Deputy Commissioner of Patents
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