Top 10 Points on Patent Applications That Refer to Nucleic Acid (Gene) Sequences or Protein Sequences

The points mentioned below apply both to where the nucleic acid or protein is claimed per se and also to situations where the invention somehow relates to use of sequences.

1.  Consider whether homologues of the sequences should be mentioned.  If so, then percentage homology ranges need to be provided and the description needs to refer to a specific algorithm that can be used to calculate the percentage homology.

2. Consider whether fragments of the sequences need to be mentioned.  If so, ranges of fragment lengths should be disclosed, and if fragments of homologues can be used then this should be made clear.

3. If homologues and/or fragments are relevant then basis should also be provided for limiting to functional sequences.  Functions apart from the natural function may also be relevant in the context of the invention.

4.  Thought should be given to claiming expression vectors that contain the sequence or express the sequence.

5.  Basis for limiting to ‘isolated’ forms of the sequence should be provided.

6.  Thought should be given to important mutants (homologues). Patent Offices are becoming increasingly strict in regards to homologues and, if possible, the application should contain details of areas that can or cannot be modified to give functional mutants.

7.  Normally it will be possible to claim antibodies that bind to novel proteins.  Thought should be given to antibodies that may cross-react to related proteins and how such antibodies could be excluded from the claims.  Antibody derivatives should also be claimed as well as use of the protein to make a specific antibody.

8. Thought should be given to claiming sequences with modified bases or amino acids.  Whether or not PNAs (peptide nucleic acids) should be claimed should also be considered.

9. Thought should be given to whether organisms containing the gene (e.g. transgenic animals or plants) should be claimed as well as organisms in which the gene has been knocked out.

10. Given the decision of the US Supreme Court in Association for Molecular Pathology v Myriad  ensure there is basis for limiting to non-natural nucleic acids, such as cDNA molecules and mutants.

You may also wish to see related articles Top 10 Observations on Antibodies and Top 10 Observations on US Restriction Requirements

Top 10 Uncertainties in Patents

This is written from the perspective of a UK-based patent attorney practising in the biotech/pharma sector.  The patenting process has many uncertainties, which makes it difficult to predict the claims which will be granted and how much the process will cost.  Here are our top 10 uncertainties:

1. Case Law and What is Patentable

Case law does evolve, and that can mean huge changes in what is patentable.  In past years transgenic plants and computer programs have become patentable.  Presently software, diagnostic methods and stem cell case law is continuing to evolve.

2. Inventive Step

How an Examiner views inventive step will often determine the scope of claims which will be granted.  However it is frequently very difficult to predict the inventive step objection which will be raised and how easy it will be to persuade the Examiner to change his/her mind.  Increasingly though Examiners are becoming stricter on inventive step in biotech.

3. Documents Identified in the Search

There is always the possibility of a surprise document being found in the search which makes patentability a lot more difficult than expected.

4. Search Problems

It can be difficult to predict whether there will be problems with the search at the European Patent Office (EPO), either in terms of lack of unity or lack of clarity.  Incomplete searches will impact tremendously on the scope of claims that will be granted.

5. Which Terms Will be Deemed Unclear in a Claim

One never knows which terms will be deemed unclear in claims.  This varies tremendously from territory to territory, with Canada being one of the strictest places on clarity.

6. Whether an Amendment Will Add Matter

Sometimes it is difficult to predict whether an amendment will be deemed to add matter.  That is particularly true if the amendment concerns combining two independent features or concerns deletion of a feature.  Strictness on added matter varies tremendously from territory to territory, with the EPO being one of the strictest.

7. Whether Functional Features Will Be Accepted in the Claims

The EPO can be very strict on whether functional features can be allowed in claims, particularly when they are used to define compounds or disease conditions.

8. Costs

There is uncertainty in the cost of a patent application through to grant because it is difficult to predict how complex examination will be.  Lengthy responses with substantial amendments may be needed, and several examination reports may issue.  In addition paying additional search fees and filing divisionals is expensive if required.  If appeal or opposition proceedings occur that will also increase costs.

9. Oral Proceedings at the EPO

Many surprising things happen at Oral Proceedings. Certain documents or arguments may suddenly become more relevant.  How the different parties will perform and whether justice will be done seems to vary markedly.

10. How Much A Patent Case is Worth

How to evaluate the worth of a patent case remains a very uncertain art.  However what it is clear is that investors at getting much better at evaluating biotech patent cases.

Top 10 Things You Need to Know About Data in Patent Applications

This is written from the perspective of a European patent attorney practicing in the pharma and biotech fields.

1.       For pharma and biotech cases data is often needed to show that the invention works, i.e. that the technical effect can be achieved by the means which are described.  A mere description of how to carry out the invention is often not enough, and a lack of data can lead to objections of lack of sufficiency, support and even lack of inventive step (problem not being solved).  The European Patent Office may use the test of whether it is ‘plausible’ the problem has been solved from the specification.

2.       Ensure that further data generated in the priority year is incorporated into the application at Convention filing.  When writing the priority application one must review whether the claims and description need to anticipate what the further data may show, for example more patient groups that could be supported by the new data.

3.       When evaluating data be mindful of identifying all technical effects, no matter how minor and making a reference to them in the description.  Fallbacks should be provided which will make it possible to limit the claims to any one technical effect if required.

4.       Ensure that the claims and description have fallbacks which represent generalised features derived from the data.  In particular consideration should be given as to whether ranges encompassing specific point values in the data need to be introduced into the claims and description.  This obviously makes it easier to amend the claims to limit them to preferred features.  However it is also a way of the Examiner appreciating the full impact of the data on the invention and on what is claimed.

5.       Don’t prejudge the problem which is solved.  That may change when prior art is identified in the search.  The patent application needs to therefore be measured in the way the data is described, and preferably should not view the data as showing a single finding.  The relevant part of the description should say: ‘The data shows that X activity of Y. It shows how Y could be used to treat Z.  It shows preferred patient groups for treatment. It shows [the different aspects of the invention]’, i.e. reflecting all the different advantages made possible by the invention.

6.       Specific advantages that should be considered beyond on the main technical effect include:

- does the data show some patient groups (e.g. with severe disease) might respond better?

- does the data indicate preferred doses, a preferred administration schedule or a preferred route of administration?

- does the data indicate other substances that could be coadministered to give further advantages?

7.       The invention might not stop at the point of administration.  Data showing pharmacokinetic properties could be useful to show additional advantages.  That could affect how the problem is defined and so assist in arguing inventive step, i.e. the problem could become ‘a substance for treating cancer with X advantageous pharmacokinetic properties’.

8.       Bear in mind that post-filing data can be filed during examination or in opposition to further support the data in the specification.  When the application is drafted that post-filing data should be anticipated if it is not available for inclusion in the patent specification.  It is difficult to predict how effective filing post-filing data will be in overcoming objections, but often it is helpful.

9.       Post-filing data used to support arguments in examination or opposition can include third party, for example data published in journal articles.

10.   Be wary of including data from other parties in the patent specification if it might affect inventorship.  Even a minor contribution can lead to a person being deemed an inventor and therefore careful thought may need to be given to which data is included in the specification if it comes from different sources.

You also wish to see related articles Top 10 drafting tips and Ways to limit a medical use claim

Top 10 Patent and Commercial Biotech Blogs

Here’s our list of favourite blogs, and why they are so good.  When choosing and ranking we’ve placed particular emphasis on whether they provide interesting articles on a very regular basis.

1.       IPKat. This is THE blog for UK and European IP developments. Fast-moving, insightful, cheeky and thought-provoking.  Unparalleled for diversity and quality in the IP blog world. Multi-authored.

2.       Life Sci VC. Bringing order and stats to the chaotic world of biotech investing.  Every aspect of commercial biotech is tackled in insightful and evidence-based ways.

3.       PatentlyO. Doggedly analysing US patent law developments in a very informative way.

4.       IPWatchdog.  Strong opinions on US patent and innovation issues. Multi-authored.

5.       Xconomy. Fast-moving diverse articles on innovation and investing. Multi-authored.

6. [Update: this blog is no longer online]       The Big Red Biotech.  It’s strength is capturing all commercial biotech developments, analysed with a concise informed wisdom.

7.       FierceBiotech. Comprehensive news from the world of commercial biotech. Multi-authored.

8.       In the Pipeline. Interesting, thoughtful, everyday thoughts on diverse pharma topics, from bench research to pharma scandals.

9.  [Update: this blog is online but no longer being kept up to date]       K’s Law.  Focused on European Patent Office case law developments, but well written and professional.

10.   IP finance.  Diverse set of articles around commercial IP issues. Multi-authored.

Top 10 Things You Need to Know About Biosimilars

1.  Biosimilars are copies of biologics produced by another party which have minor structural differences that do not substantially affect therapeutic activity.

2. Biosimilars will be produced and sold by ‘generics’ manufacturers when the patent has expired on the original biologic.

3. Given that a biosimilar is not exactly the same as the original biologic (unlike the situation with other generic drugs) biosimilars are subject to their own regulatory requirements, which are either in place or which governments are in the process of introducing.  Often a key requirement for approval is the extent to which the biosimilar could substituted for the biologic.

4. Biologics are expensive, with the US spending $320 billion on them each year.  Therefore biosimilars have the potential to give large price-savings. Estimates predict a saving of $100 billion in the US in the first 10 years of biologics being introduced.  Estimates of prices for biosimilars in the US vary between 10 to 40 % less than the prices of the equivalent biologic.

5.  Biologics producers are lobbying for strict regulation of biosimilars to delay their introduction.  This lobbying is at the government level, and in the US also at the state level.  Only Oregon, Utah, Virginia and North Dakota have passed biosimilar legislation.  This month California’s Governor voted down the Biosimilars Bill which had been passed by the California Legislation which aimed to place restrictions on biosimilars.

6. The EU recently approved its first biosimilar antibody. It was called Inflectra and is a biosimilar version of Remicade. Europe’s Remicade market is worth around $2bn.

7.  Many biologic blockbusters face patent expiry in the next 5 years (e.g. Rituxan, Erbitux, Humira and Enbrel) and so now is a crucial time for biosimilar productions and approvals.

8. The Patient Protection and Affordable Care Act created a pathway for biosimilar regulatory approval.  The FDA is working on the details of the pathway.

9.  Abbott petitioned the FDA not to approve a biosimilar for its Humira on the grounds that the FDA would have to use Abott trade secrets, previously submitted to the FDA, when carrying out the approval.

10. The top players in the US biosimilar market are expected to be Sandoz, Hospira, Teva and Amgen/Actavis.  Other players include Samsung/Merck, Pfizer, Celltrion and Boehringer Ingelheim. Outside the US Reliance, Dr Reddy’s and Biocon/Mylan are also expected to be important.

You may also wish to see related articles What do you need to know about commercial biotech and Top 10 Observations on Antibodies

Top 10 Tips on Building a Patent Portfolio

1.  Cost is a very important consideration when building a patent portfolio. In the patenting process costs spiral up, and therefore when new cases are filed, there must be an expectation that the financial resources will be available to maintain the portfolio for the foreseeable future.  Perhaps each time a case is filed the question should be asked ‘Do we expect to be able to fund national phasing of this case at 30 months?’

                         

2.  Earlier patent cases are citable against later ones.  Therefore each case needs to be drafted in a way that minimises its prior art effect on later cases. That means future research and patent applications will need to be a component of the decision-making when deciding on the contents of a patent application.

3.  A patent application is published at 18 months from filing.  It is then fully citable against later cases.  A review of the research should be conducted prior to the publication of any application to ascertain whether it is worth filing a new case before a previous case is published.  Clearly such a review should be carried out before any type of public disclosure of research is done.

4.  Ideally predictions should be made of the following into the foreseeable future:

- cost of maintaining the patent portfolio

- financial resources available for the patent portfolio

- significant research findings

These can then be used to guide the building of the portfolio, in particular how quickly it should grow.

5.  Careful thought needs to be given to whether similar inventions are filed in the same patent case or not.  Having a larger number of cases in the portfolio will give more potential for maximising the income from licencing or selling cases.

6.  Filing similar inventions in separate cases gives procedural flexibility in the patenting process.  For example if 2 cases are filed, then at 12 months one could be refiled and the other could be taken into the International phase.  This flexibility would clearly not have been possible if both inventions were in the same patent case.  However filing two cases would essentially double the patenting costs.

7.  Filing separate cases for similar inventions can be helpful in licencing them to different parties.

8.  Filing similar inventions in separate cases can also be helpful during examination where different sets of arguments and amendments could be used in overcoming objections.

9.  Having multiple patent cases allows one to have more than layer of patent protection for important inventions.

10.  Having a patent portfolio assists in giving a strong defensive position in the case where litigation is likely. In addition a portfolio of cases can be used as bargaining chips in negotiations, e.g. in a cross-licensing situation.

You may also wish to see related articles Biotech due diligence advice and What do you need to know about commercial biotech

Top 10 Things That Go Wrong With Patent Applications and Patents

1.         Filing the Patent Application Too Late

Developing technology is often a race, and if someone else gets there first it can then be very difficult to get broad claims.  Filing patent applications as soon as possible should be a priority.

 

2.         Missing a Deadline

 

There are many many deadlines to follow in the patenting process.  A lot of the work of a patent attorney is to follow and remind about deadlines.  Have a system for knowing all outstanding deadlines, and perhaps mention them at the end of every email about a patent case.  Deadlines are sometimes missed when more than one organisation is involved, for example when responsibility for paying renewal fees is given to another company.  Deadlines can also be missed when patent cases are transferred from one patent firm to another.  These are situations where more care than usual is required.

 

3.         Making the Invention Look Obvious

 

One should be careful about the way one describes the relationship between the prior art and the invention in an application.  It is easy to make the invention look obvious when it would not have been at the priority date.

 

4.         Having an Unclear Term in an Independent Claim

 

If one must rely on a potentially unclear term, then try and place it in dependent claims, with alternative definitions in the description.  Some Patent Offices can be very strict on added matter so that deleting a term from an independent claim could be seen as adding matter.

 

5.         Drafting Claim Scope Too Narrowly

 

One can always narrow claim scope during prosecution if one has to, but attempting to broaden claims can cause problems.  Claims which are overly-broad can lead to unity problems though, so careful thought needs to be given to claim scope.  Every term in the independent claims should be looked at before filing to see whether it could be broadened.

 

6.         Not Having Enough Fall Backs

 

Amendment is almost always needed during examination, and one must try to consider all the different ways the claims could be limited to overcome prior art that will be identified in the search.

 

7.         Filing the Application Without Enough Data

 

In biotech and pharma cases it is quite possible to end up with the situation where the claims are not adequately supported by the data or it’s not apparent that the problem has been solved.

 

8.         Publically Disclosing an Embodiment in the Priority Year which is not in the Priority Application

 

Ideally no public disclosures should happen in the priority year, but if they have to, then the priority application should be reviewed to see whether there is a need to file a supplementary priority application in view of the intended disclosure.

 

9.         National Phasing in Too Many Territories

 

National phasing is costly, and therefore one should be very selective in choosing the territories in which one proceeds.  Patent attorneys will not necessarily know what the best markets are for your invention, and so you should ensure you take advice from the correct sources.

 

10.     Not Abandoning Cases Which Are No Longer Commercially Useful

 

The portfolio should be constantly reviewed and cases which are no longer needed should be abandoned as soon as possible.  Preferably this should be done before national phasing to save maximum costs.  Resources spent maintaining cases might be better used filing new ones.