p a t e n t a t t o r n e y s the epo‘s approach in assessing inventive step for antibody claims...

P A T E N T A T T O R N E Y S

The EPO‘s approach in assessing inventive step

for antibody claims

Dr. Andreas Hübel

M I C H A L S K I H Ü T T E R M A N N




Article 56 EPC – Inventive step

An invention shall be considered as involving an inventive step if,

having regard to the state of the art,

it is not obvious to a person skilled in the art.



Guidelines for Examination in the EPO – G VII

2. State of the art

The state of the art may reside in the relevant common general knowledge,

which need not necessarily be in writing and

needs substantiation only if challenged (see T 939/92).




5. Problem-and-solution approach

In the problem-and-solution approach, there are three main stages:






(i) determining the "closest prior art",







(ii) establishing the "objective technical problem" to be solved, and







(ii) establishing the "objective technical problem" to be solved, and

(iii) considering whether or not the claimed invention, starting from the closest prior art and the objective technical problem, would have been obvious to the skilled person.




5.1 Determination of the closest prior art

The closest prior art is that which in one single reference discloses the combination of features which constitutes the most promising starting point for an obvious development leading to the invention.

… it should be directed to a similar purpose or effect as the invention or at least belong to the same or a closely related technical field as the claimed invention.

In practice, the closest prior art is generally that which corresponds to a similar use and requires the minimum of structural and functional modifications to arrive at the claimed invention




5.2 Formulation of the objective technical problem

- determining the difference between the claimed invention and the closest prior art in terms of features;






- identifying the technical effect resulting from the distinguishing features;







- then formulating the technical problem.







- then formulating the technical problem.

The objective technical problem derived in this way may not be what the applicant presented as "the problem" in his application.





The expression "technical problem" does not necessarily imply that the

technical solution is a technical improvement over the prior art.

Thus the problem could be simply to seek an alternative to a known

device or process which provides the same or similar effects or is more

cost-effective.




5.3 Could-would approach

Is there is any teaching in the prior art as a whole

that would (not simply could, but would) have prompted the skilled person,

faced with the objective technical problem,

to modify or adapt the closest prior art while taking account of that teaching,

thereby arriving at something falling within the terms of the claims, and thus

achieving what the invention achieves.



Inventive step for antibody claims

How does the EPO

applies its problem-solution approach

to antibody claims ??




How does the EPO


to antibody claims ?




How does the EPO


to small molecules ?



Inventive step for small molecules

Compounds not structurally close to each other

compound 1A compound 1B



Inventive step for small molecules

Compounds not structurally close to each other


Compound 1B does not have to exhibit advantages or surprising effects

beyond those exhibited by compound 1A for being considered as being

based on an inventive step.



Inventiveness of small molecules

Compounds structurally close to each other




Inventiveness of small molecules

Compounds structurally close to each other


Compound 2B has to exhibit advantages or surprising effects

beyond those exhibited by compound 2A

for being considered as non-obvious.



Inventiveness of antibodies

How is the EPO’s assessment of inventive step for small molecules

transferred to antibody claims ?

www.protopedia.org




Structure of antibodies

www.protopedia.org




Structure of antibodies




The vast majority of structural elements are the same in most antibodies.

CDR‘s constitute the gist of a novel antibody, but constitute a small portion of the antibody structure.

Amino acid sequences of the CDRs are not predictable.

Amino acid sequence of a single CDR is often known.




If antigen A is novel,

then an antibody against antigen A is usually considered to be

novel AND inventive,

provided that antigen A is well defined in the application.




• Prior Art: > monoclonal antibody (mAb) „X“, which binds protein „A“ > method for preparation (immunisation protocol, isolation) > functionality: neutralizing activity > characterized by the amino acid sequence of ist VH and VL- domains

• Claim: > monoclonal Ab „Y“ binding protein „A“, the mAB comprising the six CDRs as being those of SEQ ID NO: 1 to 6. (method of preparation is the same as in prior art, function is the same as prior art mAb)

• Novelty: > YES, due to structural characterization of the six CDRs

• Inventive:> Sequence of the six CDRs obvious ? YES or NO ?




• Prior Art: > monoclonal antibody (mAb) „X“, which binds protein „A“ > method for preparation (immunisation protocol, isolation) > functionality: neutralizing activity > characterized by the amino acid sequence of ist VH and VL- domains

• Claim: > monoclonal Ab „Y“ binding protein „A“, the mAB comprising the six CDRs as being those of SEQ ID NO: 1 to 6. (method of preparation is the same as in prior art, function is the same as prior art mAb)

• Novelty: > YES, due to structural characterization of the six CDRs

• Inventive:> Sequence of the six CDRs obvious ? YES ! pursuant to EPO




In small molecules, the skilled artisan could envisage changes here and

there, however he would not do so with an expectation to succeed

- unless prior art guides him in relation with non-active parts of the molecule

which could be modified without consequences for the biological activity or

- unless safe predictions can be made based on prior art structures.

In Ab molecules, nature does it four you => once you have a method to

produce one type of antibody, the skilled artisan knows that by routine

techniques he would succeed to produce other Abs with equivalent functional

properties, albeit different structure.




Methods of generating antibodies are known.

Köhler, G. & Milstein, C. (1975): Continuous cultures of fused cells secreting antibody of predefined specificity. In: Nature. Bd. 256, S. 495–497.

In 1979, hybridoma technology was considered not being routine (T 349/91).

Today, hybridoma technology and phage display are considered technologies that are well mastered, no technical problems are expected.

A single document describing the new technology thoroughly and reciting possible uses and advantages is sufficient to deny an inventive step.




A single document describing the new technology thoroughly and reciting possible uses and advantages is sufficient to deny an inventive step.

Hence, producing single-domain antibodies („nanobodies“) be immunisation of llamas and generating Abs by hybridomas or generating phage display does not provide an inventive step for said nanobody if said nanobody does not have an unexpected effect.




As methods for generating antibodies are considered to be routine

techniques today,

the EPO deems that structure alone can not be the basis

for acknowledging an inventive step,

if the function of the novel antibody is the same as in the prior art antibody.

The novel antibody has to have an unexpected technical effect

for having an inventive step acknowledged by the EPO.e.g. antigen specificity, affinity, mode of action, immunogenicity, stability, neutralizing titer, epitope specificity, etc.



Summary



Summary

If antigen A is novel, then an antibody against antigen A is usually considered

to be novel AND inventive,




Summary




A generic antibody against a known target is not inventive.



Summary




A generic antibody against a known target is not inventive.

The provision of a novel antibody against a known antigen involves an

inventive step only if the antibody shows unexpected properties or if it was

unexpected that such an antibody could be produced at all.



Questions to be discussed




What is an unexpected property of a new antibody ?





Is it really nature doing it for us ?






Is the basic nucleus of smalls molecule equivalent to the backbone or to the

CDRs of Abs ?







CDRs of Abs ?

Is it appropriate to consider routine techniques in assessing inventive step of

a product defined by its structure ?







CDRs of Abs ?

Is it appropriate to consider routine techniques in assessing inventive step of

a product defined by its structure ?

Is the unpredictability of CDR sequences sufficiently considered ?



Thank you very much for your kind attention.

Michalski · Hüttermann & Partnerwww.mhpatent.de

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D-40221 DüsseldorfFon +49 211 159 249 0Fax +49 211 159 249 20

[email protected]

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[email protected]

p a t e n t a t t o r n e y s the epo‘s approach in assessing inventive step for antibody claims...

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t t o r n e y s guidelines

t t o r n e y s article

closest prior art

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