The UK Bolar Exemption

These points are from a talk by Phil Bilney at Fieldfisher’s Pharma Patent Seminar on 16 October 2014.

1. A Bolar Exemption allows applicants for generic marketing authorisations under the abridged procedure to be exempt from patent infringement when conducting the necessary bioequivalence and stability studies (see TaylorWessing’s information about this here)

2. There was uncertainty about the scope of the UK experimental use exemption (s.60(5)(b) Patent Acts 1977). Directive 2001/83/EC set up the Bolar Exemption. Article 10(6) of this says:

‘Conducting the necessary studies and trials with a view to the application of paragraphs 1, 2, 3 and 4 and the consequential practical requirements shall not be regarded as contrary to patent rights or to supplementary protection certificates for medicinal products.’ [Paragraphs 1 to 4 are concerned with bioequivalents and biosimilars]

This was implemented ‘narrowly’ in the UK, and ‘broadly’ in Germany and France.

3. After a formal consultation new paragraphs 6D to 6G were inserted into s.60 of the UK Patents Act to exclude ‘anything done in or for the purposes of a medicinal product assessment’ for regulatory purposes from infringement. This derisks clinical trial studies required for any regulatory approval, including marketing authorisations and Health Technology Assessments required by the British NHS.

4. This brings the UK into line with the majority of EU member states, and makes the UK a more attractive place for clinical trials.

5. However not all uncertainty is removed. It is unclear to what extent the exemption covers research tools and also third party manufacture and supply of a drug to the party conducting the trial. In addition it is not clear how the exclusion will relate to the Unified Patent Court and how opting in and out of the Unitary Patent will affect matters.

The IPKat discusses this here.

You may also wish to see related articles 10 Points on Regulatory Data Exclusivity and 10 Points on SPC’s (Supplementary Protection Certificates).

US Biotech Claim Drafting

These points are from a CIPA seminar given by Linda Huber on 17 October 2014.

1. The following formats are relevant to biotech cases: methods of medical treatment, therapeutic compositions and diagnostic methods. Method of treatment claims usually refer treating a defined condition, i.e. ‘A method of treating disease X comprising administering compound Y’. However this is not always the case, for example: ‘A method of eliciting an immune response comprising administering immunogen ABC’. Swiss style medical use claims are not allowed.

2. Diagnostic claims are often in the format ‘A method of diagnosing disease X comprising analysing a sample for the presence of Y’. However there can be issues of matter eligibility for this claim as discussed below.

3. In the US ‘inherency’ can be a problematic issue for the novelty of method of treatment claims. A method of treatment claim is anticipated if the prior art inherently discloses the treatment due to a ‘natural result flowing from’ the disclosure. So for example if the prior art discloses drug X to treat high blood pressure in a patient, and if the drug also inhibits hair loss during the treatment, then it would be seen as ‘inherently’ disclosing this (though it does not explicitly do so), destroying the novelty of use of the drug to treat hair loss. One solution to this is to limit the claim to a class of patients that do not appear in the claim, and often this can be done by defining the patient to be ‘in need thereof’. Clearly another way would be to limit using a feature not disclosed in the prior art, such as routes of administration, etc.

4. Written description and enablement can be problematic if a method of treatment claims refers to ‘A method of preventing disease X…’. There is an assumption in US practice that no disease is 100% preventable. One can argue against such objections if there is data to show that 100% prevention is achieved. However amending the claim to refer to ‘A method of reducing the likelihood of disease X…’ can often overcome the objection. Alternatively the term ‘prevention’ can be defined in the specification as not requiring 100% prevention. Written description and enablement objections are often raised against gene therapy claims, especially where the specification does not show actual treatment. Amendment of the claim to instead refer simply to expressing the protein may overcome such objections, i.e. A method of expressing protein Y in a subject in need of treatment for disease X, comprising administering to the subject an expression vector encoding gene Z.

5. Post -AIA ‘best mode’ is still mentioned in the relevant statute, 35 USC § 112(a), but it is no longer a ground for challenging the validity of a patent. However failure to provide the best mode could still render a patent unenforceable as a matter of equity and so best mode should still be disclosed. It was noted that the specification does not need to point out what which embodiment is the best mode.

6. Two recent Supreme Court cases, Mayo v Prometheus and Association for Molecular Pathology v Myriad Genetics, have had a huge impact on biotech patents. Mayo concerned a claim to a method for optimising therapeutic efficacy of a condition by assessing the in vivo level of a particular metabolite to determine the amount of drug to administer. The Supreme Court held the method to relate to a ‘law of nature’ and therefore to be ineligible matter. In addition the ‘application’ of a law of nature is also unpatentable if it merely relies on elements already known in the art. The ‘take home’ message from Mayo is that the invention must not too broadly pre-empt the use of the law, and should include an inventive concept which is significant and separate from the natural law.

Myriad decided that genomic DNA was not patentable since it was part of nature, and separating a gene from the surrounding genetic material (so it is ‘isolated’) does not make it an invention. However cDNA is patentable because it does not occur in nature and its sequence is created in the lab. Part of the logic of the decision is based on the fact that the ‘information’ in genomic DNA is unchanged by isolating it, and therefore it would seem that the logic would not apply to other molecules. However, as discussed below, new USPTO guidelines have applied the Myriad principle of ‘naturally occurring molecules being unpatentable’ to all molecules. It was noted that the Supreme Court’s decision Alice v CLS Bank had little impact on biotech cases.

7. The USPTO issued new guidelines in March of this year in view of Mayo and Myriad. They give examples of what is patent eligible and seem to have broadened the principles set out in Mayo and Myriad. They are also quite unclear as to what is patent eligible. The guidelines provide a 3 part test for patentability which determines whether the invention provides something ‘significantly different’ from a judicial exception (abstract ideas, laws of nature or natural principles, natural phenomena and natural products). The guidelines list ‘factors that weigh toward eligibility’, such as:

- the claim providing meaningful limits on scope so that others can use the judicial exception,

- the claim reciting a particular machine or transformation of an article which integrates the judicial exception into a particular application, or

- the claim recites one or more elements which are more than well-understood, conventional or routine.

8. From the examples given in the guidelines it is clear that the level of ‘generality’ of an invention is important in determining its eligibility. Simply identifying mutant gene sequences in an individual by comparing to wild-type or treating a condition by exposure to sunlight are ineligible. However diagnosis using a specific defined antibody and flow cytometry is given as an example of a patent eligible invention.

9.The guidelines are clearly going to be problematic for diagnostic claims which are normally based on measuring the level of a natural product or characteristic. One possible solution is to refer to specific reagents, such as a novel antibody, in the claim. Alternatively one could introduce a treatment step into the claim. However the recent Supreme Court decision Limelight v Akamai made it more difficult to find infringement where split infringement occurs, and so it could be difficult to enforce claims which had diagnostic and treatment steps as they are likely to be performed by different parties. One way to avoid having these two distinct steps in the claims is to refer to have a first step which refers to ‘obtaining the results of a diagnostic analysis’, rather than performing a diagnosis. Other solutions include having a ‘system’ claim referring to the components of the diagnostic assay, claiming the relevant protein-antibody complex which is formed during diagnosis or writing the claim as a ‘method of selecting a treatment for disease X…’. Narrowing the scope of the claim should be helpful in overcoming eligibility issues.

10. For product claims, it will be important to find ways in which the product is structurally different from nature. Referring to ‘synthetic’ or ‘recombinant’ DNA may work or requiring that the natural sequence is linked to another ‘heterologous’ sequence may also succeed. For cells and organism the feature of being ‘transgenic’ may also be enough to distinguish them from nature.

11. It is not clear how the guidelines will impact method of treatment claims. Some Examiners are taking the view that administering a naturally occurring polypeptide is ineligible matter. Clearly it would be wise to have fallbacks in the specification that could be used to limit the claims, for example specific administration schedules and routes of administration.

You may also wish to see related articles 8 Points on the US Supreme Court Decision Limelight v Akamai and Building a Patent Portfolio.

Bits and Pieces on Inventive Step, Biotech Patenting, Big Data and Derisking Biotech

1. Here’s a slightly old, but interesting, article we discovered from the Singapore Academy of Law on ‘The Future of Inventive Step in Patent Law’.

2. Today our post ‘An Overview of Biotech Patenting’ was published on K2/Keltie’s blog IPCopy. Our intention was to set the scene for a series of articles which will explore the idiosyncrasies of biotech patenting and how it needs to fit into commercial considerations.

3. We came across this HBR article ‘Let Data Ask Questions, Not Just Answer Them’ which is about use of big data for hypothesis generation, rather than finding solutions. Clearly big data has a lot of evolution to do before it can be fully utilised.

4. We think ‘Target Practice’ on the Life Sci VC blog asks a lot of pertinent questions for people setting up biotech companies. It summarises the commercial considerations that need to go into research projects and suggests approaches that help to minimise risk.


Types of Equivalents in Biotech Patenting

Patent claims should cover the broadest expression of the ‘technical effect’ which is possible, and part of the art of a biotech patent attorney is to be able to draft claims having considered the equivalents of all the features present. Here are our favourite equivalents:

Homologues of Sequences

Whenever specific protein or nucleic acid sequences are mentioned thought should be given to homologous sequences that might be able to provide the same function. That function might not necessarily be the natural function of the sequence. For example for a vaccine invention the equivalent might have the same antibody or T cell epitopes. Homologues are normally defined by means of a minimal percentage homology to a specific sequence. In this case the specification should also give an example of an algorithm that can be used to calculate homology, though I have never come across an instance of an Examiner requiring the algorithm to be mentioned in the claims. In the example below the required function is to be able to tolerise an individual.


  1. A composition for use in preventing or treating allergy to ragweed by tolerisation comprising: (i) at least one original polypeptide selected from RGW03B, RGW03A or RGW03 (SEQ ID NO’s. 9, 8 or 7) or a variant thereof; (ii) at least one original polypeptide selected from RGWOl, RGWOlA or RGWOlB (SEQ ID NO’s. 1, 2 or 3) or a variant thereof; iii) at least one original polypeptide selected from RGW04 or RGW04A (SEQ ID Nos: 10 or 11) or a variant thereof; and (iv) optionally one or more original polypeptides independently selected from any of SEQ ID NO’s. 4-6 and 12-31 or variants thereof; wherein said variants are: (a) a polypeptide of length 9 to 20 amino acids that comprises a region consisting of: the equivalent original peptide sequence; or a homologous sequence which has at least 65% homology to the equivalent original peptide sequence, which sequence is capable of tolerising an individual to the equivalent original peptide sequence, or (b) a polypeptide of length 9 to 20 amino acids that comprises a region consisting of a sequence that represents either: a fragment of the equivalent original peptide sequence; or a homologue of a fragment of the equivalent original peptide sequence, which sequence is capable of tolerising an individual to the equivalent original peptide sequence and has a length of at least 9 amino acids, and wherein said homologue has at least 65% homology to any 9 contiguous amino acids in the equivalent original peptide sequence.

T cell Epitopes

Equivalents of T cell epitopes will be sequences that bind to the same T cell receptor. Examiners may not be too pleased to see sequences defined in terms of what they bind to. The example below shows the sorts of equivalents that could be considered.


  1. A method of diagnosing coeliac disease, or susceptibility to coeliac disease, in an individual comprising: (a) contacting a sample from the host with an agent selected from (i) the epitope comprising sequence which is: SEQ ID NO: 1 or 2, or an equivalent sequence from a naturally occurring homologue of the gliadin represented by SEQ ID NO : 3, (ii) an epitope comprising sequence comprising: SEQ ID NO : 1, or an equivalent sequence from a naturally occurring homologue of the gliadin represented by SEQ ID NO : 3, which epitope is an isolated oligopeptide derived from a gliadin protein, (iii) an analogue of (i) or (ii) which is capable of being recognised by a T cell receptor that recognises (i) or (ii), which in the case of a peptide analogue is not more than 50 amino acids in length, or (iv) a product comprising two or more agents as defined in (i), (ii) or (iii), and (b) determining in vitro whether T cells in the sample recognise the agent; recognition by the T cells indicating that the individual has, or is susceptible to, coeliac disease.

Single Nucleotide Polymorphisms (SNP’s)

SNP’s are often ‘associated’ with other SNP’s, i.e. they tend to be found together in genomes. This is termed ‘linkage disequilibrium’. Diagnostic tests that detect the presence of a particular SNP could also be based on detecting SNP’s which are in linkage disequilibrium with it, and so it is worth thinking about whether to attempt to claim those other SNP’s. See the example below. [The Trilateral Report on SNP’s (see here) provides useful guidance on how Patent Offices assess their patentability]


  1. A method of testing a dog to determine the likelihood that the dog is protected from liver copper accumulation, comprising detecting in a sample the presence or absence in the genome of the dog of one or more polymorphisms selected from (a) SNP ATP7a_Reg3_F_6 (SEQ ID NO: 142) and (b) one or more polymorphisms in linkage disequilibrium with (a).

Crystal Factors and Crystal Structures

Where the feature is essentially a numerical value or a set of values then careful thought may be needed as to how to cover equivalents. X-ray diffraction data (structure factors) and structural coordinates obtained by crystallography are an example of this. As can be seen from the claims below equivalents can be defined in terms of being ‘obtainable’ by the relevant crystallographic method. [The Trilateral Report on claims relating to 3D structures (see here) provides guidance on how Patent Offices will examine such subject matter]


  1. Use of the structure factors obtainable by subjecting a crystal comprising at least an epitope binding fragment of the SM3 antibody, bound to a peptide recognised by the epitope binding site of SM3 to X-ray diffraction measurements to identify, screen, characterise, design or modify a chemical entity.
  2. Use of the structural coordinates obtainable by subjecting a crystal comprising at least the epitope binding fragment of the SM3 antibody, bound to a peptide recognised by the epitope binding site of SM3 to X-ray diffraction measurements and deducing the structural coordinates from the diffraction measurements, to identify, screen, characterise, design or modify a chemical entity.

You may also wish to see related articles Top 10 Points about Gene and Protein Sequences and 10 Points on Patent Applications Directed to SNPs (single nucleotide polymorphisms).

Bits and Pieces: Value of Weak Patents, Assessing CETA and the Contribution of Academic Knowledge to Industry

Here are three publications that caught our eye:

  1. The Value of a ‘Weak’ Patent (see here)

A Monte Carlo simulation is used to value weak patents in this interesting study. Liu finds the value of weak patents to be affected by litigation risk. Whether or not one agrees with this finding it raises interesting questions about the strategies around weak patents, and perhaps helps decision-making on how much resource to devote to them.

  1. Making Sense of the CETA (see here)

This is a study of the Canadian-European Union Comprehensive Economic and Trade Agreement. It is very detailed and has caused controversy. It is of interest to us as providing a possible framework to look at the fairness of trade agreements in general. The study focuses on provisions to allow corporations to seek compensation from governments outside of the regular court system. That will undermine environment protection measures, public health policies and other public interest legislation.

  1. The Contribution of Academic Knowledge to the Value of Industry Inventions (see here)

This study finds that inventors benefit more when they can gain theoretical academic knowledge from universities, rather than simply solutions to specified technical problems. Perhaps this offers insights to how best to university academic knowledge in advancing technological progress.

Patent Bits and Pieces: the Future of the Federal Circuit, When Can You Amend in UK Litigation, Non-Patent Incentives, Patent Pools and Personalised Medicine

Here’s a collection of interesting items we recently came across:

1. ‘Coming of Age for the Federal Circuit’ is a paper by Professor Feldman about what the Supreme Court is trying to tell the Federal Circuit through recent decisions.

2. A recent UK High Court decision, Compactgtl v Velocys & Ors, sets out when amendments are allowable during litigation. See the decision here. See the IPKat post about it here.

3. ‘Patentable Subject Matter and Non-Patent Innovation Incentives’ is a paper by Lisa Ouellette asking Courts to think about non-patent incentives to assist in defining what is patentable.

4. ‘Patent Law’s Problem Children: Software and Biotechnology in Trans-Atlantic Context’ is a paper by Dan Burk examining the issues around patenting software and biotechnology.

5. ‘Power and Governance in Patent Pools’ by Michael Mattioli studies 52 patent pools to see how they operate and proposes initiatives which could help patent pools promote innovation.

6. ‘Reviving the Paper Patent Doctrine’ by John Duffy explores whether Courts should discriminate against enforcement of patents which are not practiced.

7. ‘Incentives, Intellectual Property, and Black-Box Personalised Medicine’ by Nicholson Price II looks at the patenting of personalised medicine inventions based on algorithms in view of the Mayo, Myriad and Alice decisions.

8. ‘Personalised Medicine and Patent Eligibility’ by Steven Amundson looks at the effect of the Akamai, Mayo and Classen decisions on patenting personalised medicines.


Evergreening in the Pharma Sector

A recent IPKat post (see here) about adoption of a resolution (see here) about second medical use claims at AIPPI has led to some interesting Anonymous comments which discuss the controversy over evergreening.

This caught our attention because of two interesting points cited by the comments:

- The UK decision Les Laboratoires Servier and Servier Laboratories Limited v Apotex Inc, Apotex Pharmachem Inc Apotex Europe Limited and Apotex UK Limited [2008] EWCA Civ 445 (see here for the decision, see here for the IPKat post). In the decision Robin Jacob made some very harsh comments against evergreening.

- Robin Jacob’s comments on evergreening in the pharma sector (see here) which were part of the EU enquiry into the sector.

This is clearly a controversial area, but the role that second medical use claims can play in effectively extending protection beyond the initial term has to be acknowledged.

You may also wish to see related articles 10 Points About the State of the Pharma/Biotech Sector and 10 Observations on Different Types of Research.