Patents and Licenses (02, 2019) - "Antibody patents: Claims expressing essence of invention"

14 February 2019

Antibodies have great potential, being a versatile, understandable and very convenient designer of drugs of directional action. Therefore, the correct characterization of antibody-related inventions in the claims is crucial for stimulating progress in relevant areas of medicine as considered by Sojuzpatent LLC key specialists M. V. Kuptsova and T. N. Badaeva,

Keywords: antibody, Fc, amino acid sequence, patent, claims, essential feature, problem to be solved, contribution to the state of the art.

Introduction

The antibody characterizing features in the claims are given unreasonably little attention in the Russian professional literature. Therefore, the article by E. B. Gavrilova and T. S. Babakova “Characterization of an Antibody as a Technical Solution”1 and the authors’ appeal for discussion is good news. We decided to respond to this appeal, and we hope that other specialists working with similar objects will also express their opinion on the issues raised in this article.

First, we turn to the inventive development in the field of antibodies and related economic aspects.

Some history and economy

In 1889, Paul Ehrlich, conducting experiments on rabbits, realized that certain protein molecules were overproduced during immunization. Passive immunization of a human was carried out in 1891.2 In 1959, G. M. Edelman and R. R. Porter independently clarified almost completely the most significant issues concerning the nature and function of antibodies and won the Nobel Prize in 1972.3 In 1975, G. J. F. Köhler and C. Milstein donated to the world a method for producing monoclonal antibodies; in 1977, A. F. Williams showed that a monoclonal antibody can be obtained for any molecule of interest.4 Recent discoveries have created a fertile ground for the application of recombinant DNA technologies already known to receive antibodies. In 1989, US Patent # 4816567 with a priority from 1983 on the genetic engineering method for producing antibodies was granted to Genentech, Inc.

The recombinant DNA method, coupled with the impressive ability of the immune system to generate a specific antibody to essentially any substance, making negligible changes to its “slingshot structure,” is a universal, understandable and very convenient designer. The possibilities of researchers working with him are essentially limited only by their imagination and market needs.

As for the latter, according to the Grand View Research, in 2016, the global market for research in the field of antibodies was estimated at $ 2.52 billion.5 At the same time, by 2025 the expected market growth will be 6%. The amount of funds invested in the development of innovative products is impressive. For example, in 2016, Novartis invested $ 9.0 billion, and Pfizer invested $ 7.9 billion. The growing incidence of cancer and other chronic diseases contributes to increased investment. Thus, over the past 10 years, the annual number of first diagnosed malignant neoplasm cases in Russia increased by 120 thousand.6

Four of the five drugs with the highest sales in the world are antibody-based drugs.7 Here the commercial success of therapeutic antibodies is generally associated with their higher efficiency and with fewer side effects as compared to those of chemically synthesized drugs.

However, the financial risk associated with the development of new products or the creation of new knowledge has always been and remains great. Therefore, companies investing in the creation of new antibodies must have a definite guarantee of financial return from investments in R&D in the form of know-how and patents, which are given the greatest preference, since antibodies can be reproduced by reverse engineering. For example, some companies offer to install a sequence of antibodies for $ 840 for six days.8

Thus, patent protection of intellectual property in the development of new antibodies in the territory of the Russian Federation is of paramount importance.

Technical solutions embodied in antibodies

In our opinion, antibodies can embody essentially different technical solutions characterized by the sets of their inherent essential features. Meanwhile, depending on the problems to be solved and the effects to be achieved, such solutions can be divided into at least five groups, and each of them can be characterized by the own essential features to be revealed.

The first group is related to identifying a new useful target. The unlimited examples of such targets include a substance involved in the occurrence/development of a disease, markers of biological structures and biological processes. Detecting such targets requires an enormous amount of work with minimum guarantees of success and a return of investments. But obtaining antibodies to this new target will normally cause no further problems. Therefore, the essential features of the first group solutions adequately reflecting their essence and contribution to the art will be the bound antigen features, for example, its structure and location. The essential features can also include the effect provided by the antibody-target binding.

The second group includes the inventions based on identifying the optimum epitope on the target. So, the antigen data is sometimes insufficient to get its specific antibodies. For example, the target antigen structure can almost repeat the structure of another substance, which effect is highly undesirable. In these cases, in order to obtain antibodies of the desired specificity, a work is required for finding the optimum epitope, for example, one that distinguishes the antigen of interest from non-target substances. When compared with the search for a new target, the work of identifying the optimum epitope on the target requires less effort, and the success and return of the investments can be more or less guaranteed. Therefore, the adequate essential features of such inventions of the second group will be the features of the identified optimum epitope.

The third group includes the inventions related to the production of new, more effective antibodies against a known target antigen or epitope. The creation of such inventions is usually a painstaking, but rather routine work. Therefore, with a certain amount of time and money spent, success is almost guaranteed. The essential features of such solutions may be the sequences of antigen-binding sites, namely the CDRs, since the effectiveness of antibodies largely depends on the configuration of such sites. Antibodies that embody these technical solutions can also be characterized by their generating cell line (hybridoma).

The fourth group includes the inventions related to the production of new antibody derivatives. Here note that, although traditional four-chain antibodies are highly specific, some of their properties, such as large size, often bifunctionality and immunogenicity, create great difficulties in practice. Therefore, there is a need to obtain derivatives of molecules that differ from traditional antibodies by a number of properties, with the exception of antigen specificity.9 Obtaining such derivatives requires the discovery of new functional relationships between the individual structural units of the antibody and its behavior in the body. This is a difficult job, but if successful, the invention gets the widest application, since it allows you to create "superbinding" agents with new properties to a variety of targets. The difference between traditional antibodies and traditional ones will be the structure and/or arrangement of the parts that are not related to antigen-binding. Therefore, the essential features of such inventions will be the compilation and mutual arrangement of the functional parts of the antibody.

The fifth group includes the inventions related to the creation of antibody derivatives. Their development is due to the need to change in the desired direction the properties of antibodies or their known derivatives such as: half-life, penetrating power, etc., including properties that lead to the occurrence of adverse reactions during therapeutic use. For this purpose, minor changes are made to the conservative regions of already existing molecules, which, as a rule, do not affect the CDRs. The conservatism of variable regions makes the probability of success small, since making changes to it often disrupts the functioning of the molecule. However, if the desired beneficial change is detected, then, as a rule, a variety of antibodies to different antigens or their derivatives can be improved. Therefore, such inventions are of great social interest. The essential features of such inventions are the specific change in the structure, location and characteristic of the improvement provided thereby.

Here note that the diversity of inventions in the field of antibodies is constantly increasing. Therefore, there is an actual problem of identifying the adequate antibody features in the claims.

Antigen features in claims, regulatory requirements and world practice

As is known, Russian and Eurasian patents are valid in the Russian Federation. Further, we focus on the regulatory documents of the Russian Federation.

According to clause 53(3) of the Requirements to the application file for granting the patent of invention (hereinafter referred to as the Requirements), the claims must clearly express the substance of invention and contain a set of essential features providing achievement of the technical result. Thus, the claims should comprise only the essential inventive features rather than a template set of characteristics inherent in one or another subject matter.

Indeed, the regulatory documents comprise a number of formal terms to characterize the subject matter in the claims. However, they are not needed at all in order to become the “Procrustean bed” into which the invention is squeezed, cutting off undesirable essential parts and pulling insignificant ones to the forefront. On the contrary, all these requirements are designed to help describe the created invention and provide an adequate (correct) scope of protection.

The complex structure of antibodies can be attributed to both polypeptides and protein structures. Accordingly, taking into account clauses 53(13) and 53(20) of the Requirements, the following options are possible for its characteristics in claims:

characterization through the complete amino acid sequence;

characterization of a part of the amino acid sequence;

characteristic features of design performance;

characterization through other properties and, possibly, further physicochemical features if they distinguish it from known antibodies.

Regarding the latter option characteristics, there are some ambiguities. Thus, clause 10.8.3 of the Administrative Regulations contained a similar condition for polypeptide characterization in the claims: "physicochemical and other features that allow distinguishing the given compound from others."

However, according to the interpretation of this condition in clause 10.3 of the Guide for substantive examining applications for inventions (hereinafter referred to as the Guide), the indication of physicochemical properties was not mandatory but actually allowed characterizing a polypeptide only by other features.

It is still unknown how exactly the similar condition of the Requirements will be interpreted in the future. In our opinion, in the case of polypeptides, physicochemical features are often inessential and rarely distinguishing. Therefore, as we see, these features should not be mentioned separately in the regulatory documents among the features that can be used to characterize a polypeptide in the claims.

Refer to the experience of foreign patent offices. First, note that none of the relevant regulatory documents comprises a closed list of features that could characterize a polypeptide or antibody in the claims (see, for example, chapter V of the European Patent Convention on patenting of biotechnological inventions). As it follows from the processing practice of applications at the European Patent Office, an antibody can be characterized by a target to which it is directed, features of an epitope on a target, a functional property (for example, determining a new therapeutic use), a sequence, a hybridoma or other method of preparation.10

In our opinion, the regulatory documents of the Russian Federation prescribe the general antibody features in the claims that allow implementing the antibody characterization approaches that are practiced by other patent offices and are due to the current art development. This fact should inspire optimism in view of the fact that estimating sufficiency of a particular inventive feature needs the prior art, which is defined equally in most patent offices and includes any information that has become publicly available in the world before the priority date of the invention.

In our opinion, a positive feature of the existing regulatory documents of the Russian Federation, is that the claims do not provide a close list of features characterizing polypeptides, including antibodies. As we understand, there is an indisputable recognizable fact that it is impossible to predict in advance the course of inventive thought and to determine the essential features that can characterize really pioneering future inventions in the field of polypeptides and, in particular, antibodies.

For the future development in this field, it is very important to retain the existing ability to characterize antibodies by other features.

Problematic variants of antibody features

Indeed, single-type characterization of inventions (for example, characterization of inventions in the field of antibodies only by amino acid sequences of CDRs) is always more clear and convenient. Therefore, we are aware that our opinion that antibodies can and should be characterized by different features, depending on the nature of the inventions embodied in them, may be unshared. We also realize that there may be concerns about certain antibody features that are often found in international applications filed under the PCT procedure. Refer to the “alarming” features of antibodies.

So, the antibody producing hybridoma is deposited (specifying the international depositary abbreviation and deposit number). Such characteristics may raise questions as they reveal neither the antibody features nor those of the producing hybridoma, in particular, the features of the latter are replaced by a reference to the physical location of this cell line, which is inaccessible, for example, for testing by a patent examiner.

To begin with, each individual hybridoma synthesizes an antibody of a certain specificity with the same unique structure, being capable of unlimited growth in an artificial medium and reproducible only by cloning.11 By obtaining an antibody from a hybridoma, one can be sure that it is unique and has not been obtained by anyone else. Therefore, if the hybridoma is deposited, and the properties of the antibody are verified and confirmed, it can be said that the applicant has given all the comprehensive information about the antibody, which will allow it to be obtained, used and distinguished from others.

The article by E. B. Gavrilova and T. S. Babakova described a case in which different groups of researchers announced the production of hybridomas producing the same antibody. However, such a case is the result of unfair competition rather than the evidence that the above is incorrect. For example, in the case under discussion, the possible unfairness of one of the research teams is evidenced by the fact that the same hybridoma was obtained twice (which is unlikely by itself), and that it was obtained almost at the same time (which is almost impossible). Therefore, this case was successfully resolved.

What guarantees gives depositing a hybridoma? First of all, it is a guarantee of reproducibility. However, this is a guarantee not only of the possibility of obtaining an antibody from this hybridoma, but also of the fact that the hybridoma produces it.

Thus, in accordance with the Budapest Treaty on the Recognition of the Deposit of Microorganisms for the Purposes of the Patent Procedure, the viability of the deposited hybridoma, as well as its unpolluted status, must be maintained by the International Depositary. In particular, clause 9.1 in Rule 9 of the Budapest Treaty Instruction stipulates that a deposited microorganism must be stored so that it remains viable and uncontaminated for at least 30 years from the date of deposit. Regarding the latter term, it should be clarified that the lost capacity of producing antibodies or an antibody with the original structure clearly indicates that the initial deposited hybridoma is contaminated or completely replaced by foreign degenerate cells.

Though neither the Instruction nor the Budapest Treaty regulates the conditions of storage of deposited material in the depositories, nevertheless the said term of clause 9.1 in Rule 9 of the Instruction imposes certain obligations on the international depositaries, whereby the said conditions must safety retain viability and microbial non-contamination. For example, this is ensured by the fact that the depository stores a biological material in the frozen or lyophilized condition, which ensures its safety for many years.12

The particular storage conditions are determined by the properties of the specified material and, on the one hand, cannot be described for all types of microorganisms and hybridomas that can be deposited, and, on the other hand, the storage conditions for each specific deposited material are communicated by the depositing persons to the international depositary as prescribed by clause 6.1 in Rule 6 of the Budapest Treaty Instruction. These persons should be certainly interested in the safety of the deposited material, since the absence of the deposit of a patented hybridoma may lead to the revocation of the patent.

Therefore, there is no doubt that a deposited hybridoma retains the ability to produce the claimed antibody for the entire term of the patent since the opposite would indicate the illegitimacy of the Budapest Treaty itself and/or the inability of the international depositaries to fulfill the obligations under clause 9.1 in Rule of the Budapest Treaty Instruction.

An antibody that binds to antigen X/epitope of Z sequence. The main objections to this feature relate to reproducibility of such an invention, as well as to distinguishing an antibody with this feature from others when evaluating the invention patentability.

First of all, remind that the patent offices of different countries accept this feature if there is a known antigen X is known (or epitope Z, which is a specific place on the same known antigen), i.e. the given feature is sufficient to obtain an antibody. Indeed, as was noted in the historical section, there are already well known and developed methods for producing antibodies to existing antigens. For example, a single-step immunizing a mammal with an antigen can produce numerous antibodies with the required antigen specificity and different CDRs, since this is the basic property of a healthy immune system. Accordingly, such method could hardly omit antibodies of the desired specificity.

In this regard, characterization of antibodies at the functional level may be justified if no antibody has been earlier obtained to antigen X/epitope Z. In addition, this feature does not break the RF regulatory documents prescribing applicability of functional generalization for a feature characterized in the claims (see, for example, clause 45 of the Requirements).

As for the distinctive ability of this feature, if the antigen to which the antibody is obtained was not previously known, then it is obvious that the feature “antibody binding to the said new antigen” automatically distinguishes all antibodies produced for this antigen from the others described in the art of antibodies.

When the claims characterize an antibody is characterized as binding to epitope Z on antigen X, which antibodies are known, only at first glance it seems that it is impossible to estimate the invention novelty and inventive step. Generally, binding of antibodies to a specific epitope of an antigen is expressed in certain effects. The fact of known or unknown effects enables judging whether the antibodies encompass those binding the particular epitope.

If the examiner still has difficulties, he can send the applicant an official action motivated by the fact that it is impossible to estimate whether the known antibodies are able to bind the same epitope and the advantages arising from such ability. Further, in the course of such correspondence, it will be possible to establish the truth: whether the pending invention satisfies the patentability conditions of novelty and inventive step.

Finally, do not forget that an unlawfully granted patent can be revoked by the concerned market participants on the basis of evidence (for example, in the form of relevant experimental data), that the epitope under the invention is bound by the antibodies known on the patent priority date of the said invention.

Antibody … having altered Fc fragment …

With this characteristic, as a rule, the antigen specificity of the antibody is not indicated, but its improved property is indicated. Therefore, the stumbling block in this case is the purpose of the antibody: whether its activity (antigenic specificity) should be specified, or some other biological properties of the substance can be indicated to determine the purpose. If we formulate this question more broadly, then it may sound as follows: does the invention purpose correspond to the function of the subject matter embodying the invention, or the does the invention purpose corresponds to the problem to be solved by the authors of the invention? In our opinion, both answers may be correct.

This view is supported by 10.3. of the Guide, whereby “the claims characterizing the modified forms of natural polypeptides known from the prior art may be sufficient if the known substance (basic structure) title is specified together with the relevant variable region (location, position of amino acid residue, site), the nature of the change and property to be acquired”.

In view of the foregoing, for a modified polypeptide, it is necessary to specify the properties to be acquired by it as a result of the modification, i.e. the problem to be solved by the inventors rather than the activity of the substance.

Referring again to the antibodies described as “an antibody that has an effect ...”, note that such an indication reflects the purpose of the invention, that is, for what specific purpose it can be used in a particular field. In particular, the indication of a positive effect refers not only to new beneficial biological properties of the given substance but actually to the specific purpose for which it can be used in industry, healthcare or other fields. Thus, the inventive “antibody with an extended half-life” can be used in healthcare for various therapeutic antibodies with very different antigen specificity for obtaining drugs with improved pharmacokinetics on their basis.

In addition, remind that the very title of “antibody” is obviously a possible purpose of the subject matter, since the antibody application fields are generally known. They comprise therapy, diagnostics, and various studies, where antibodies can be used as a label, and many others.

Surely, if no specific antigen specificity is indicated, it can be a matter of the validity of the scope of claims expressed by the broad generic term “antibody”, in view of clause 56 of the Rules for drafting, filing and processing the documents serving the basis for performing legally significant actions on the state registration of inventions, and forms thereof. But, as was already noted, a useful mutation in the Fc region allows for the improvement of antibodies with strongly varying antigen specificity (that is, regardless of antigen specificity). Therefore, in this case, the claims within the scope of the purpose arising from the title of antibody appear legitimate and should not be limited by antigen specificity.

In summary, note that the invention purpose embodied in the antibody (as well as in any other polypeptide), should express its intended use. However, it does not have to coincide with the type of activity and may be associated with a biological function. In the case of inventions related to detecting useful mutations in the Fc region, the purpose is determined by a new biological property of interest, objectively manifested by the mutation, and it seems impractical to restrict it further with the antibody activity.

Possible consequences in the case of the using “problematic” antibody characteristic variants in the claims

There are concerns that the above-described “problematic” antibody characteristic variants in the claims may lead to conflicts between bona fide market participants who may inadvertently violate a patent, and to the emergence of so-called umbrella and evergreen patents.13 But only at first and a very superficial glance it may seem that to prevent such situations it would be beneficial to grant patent rights to antibodies in a limited scope, regardless of the invention, including its contribution to the prior art.

Remind that antibody drugs can be are quite easily reproduced by reverse engineering, and the volume, and, therefore, the cost of the clinical studies required for the state registration of for reproduced drugs (generics) is lower than that of the original ones. In particular, according to clause 10 in Article 18 of the Russian Federal Drug Circulation Act No. 61-FZ of April 12, 2010, “for the state registration of reproduced drugs for medical use it is allowed to submit … instead of full clinical studies ... a report with the results of bioequivalence studies of the reproduced drug for medical use”.

Thus, provision of a narrow patent protection within the amino acid sequence will allow the original drug developer to suspend the market introduction of corresponding generic drugs only for those who are not actually involved in development of antibodies, but will not protect against clearly numerous real competitors, for the following reasons:

expected growth in the global antibody market will be 6% until 2025;14

numerous different antibodies can be produced to the same antigen;

developers currently have access to not only animal immunization technology followed by humanization of the resulting antibody, but also antibody or fragment library art, which allows selecting quickly an appropriate human antibody to the antigen, as well as antibody affinity maturation technologies, which allow required antigen binding characteristics.

Accordingly, patent protection in the scope of the amino acid sequence of antibodies cannot ensure the return of funds spent on research, not to mention profit, for example, if the developer has not just created a specific antibody but conducted very laborious and knowledge-intensive research to develop it to the substance with unknown contribution to pathogenesis of the disease. If the product turns out to be commercially successful, it will attract the attention of other market participants, who can create their own antigen antibody without violating the developer's patent.

In the authors’ opinion, the more global is the problem solved by the invention, the more resources are required to create it, and the more patent rights are required by the concerned persons in order to decide on investments.

In addition, these concerns do not seem to be fully justified.

So, by definition, an umbrella patent is not a practice backed up or overly general patent, the purpose of which is to condemn someone who can put the technology into practice.15

Meanwhile, the patent applications for an antibody-related invention generally comprise the relevant experimental data demonstrating the provided beneficial effect, for example, the effect of an antibody binding a new antigen or the effect of introducing a mutation into the Fc region of an antibody.

Note that, in most cases, the purpose of these patents is providing not obstacles to clinically significant products entering the market but crucial protection of the field of art being developed, in particular, due to the abundant known opportunities of circumventing the antibody patents. For example, if an invention relates to introducing mutations in the Fc region, remind that the mutation is introduced into a previously known amino acid sequence of this region. This means that all previously known antibodies do not include such a mutation (otherwise the patent would not be granted due to non-compliance of the invention with the patentability condition of novelty) and do not violate the patent, while developers of new antibodies can use the well-known Fc without mutation or even obtain a new product in a format that does not principally require an Fc region to be present.

It should be recognized that the patents protecting the antibody that binds to antigen X provide a very wide protection scope, but it cannot be classified as overly general or unjustified. After all, if an antigen or its contribution to the pathogenesis of the disease is unknown, the development of a therapeutic antibody includes studies that are more global than studies that take place when the antigen and its function are known. At the same time, having disclosed the obtained information about the antigen and the effect of exposure to it, the developer essentially provides everyone with the opportunity to develop and patent the own antibody to the antigen. Therefore, the only protection of funds invested by the developer in discovering a new antigen and identifying its role will be only a patent for an antibody characterized at the functional level, namely, binding to the antigen, and the scope of claims is fully justified.

In relation to evergreen patents, first of all, the terms should be defined. So, evergreen patents can be considered as a series of patents related to the same substance, where the invention in the subsequent patent differs from the invention in the previous patent by minor modifications.16

Note that quite often one can observe the situation of misusing this term, that is, when a series of patents obtained during the development of a medical substance are referred to as evergreen patents. This situation will be explained in more detail in connection with antibodies.

The development of a therapeutic antibody begins with the definition of an antigen and its role in the pathogenesis of the disease. If both are known, then first it must be obtained, to put it simply, the set of “draft” antibodies that bind to the antigen more or less specifically. Often, laboratory animals are used to obtain them and create hybridomas that produce antibodies that are not intended to be administered to humans. Therefore, patent for a hybridoma and an antibody produced by a hybridoma is often a patent for a product that will never be marketed as a therapeutic product.

Next, the researchers determine the sequence of the best “draft” antibodies as the basis for obtaining humanized or fully human antibodies by genetic engineering. Moreover, the antibody in the claims of the corresponding patent is characterized by a sequence that is not generally a sequence of a “draft” antibody. Thus, in view of developing a new therapeutic antibody and the logic of relevant patenting, a patent for an antibody characterized by hybridomas and a patent for an antibody characterized by a sequence cannot be considered as patents for the same substance.

Finally, we should discuss the possible situation of a conflict of interest caused by the fact that the developers of therapeutically significant antibodies to specific antigens unintentionally created an antibody that falls within the scope of protection established by the patent with a problematic antibody characteristic. For simplicity and clarity of discussion, refer to the same example as the authors of the aforementioned article17, viz. to an antibody characterized by mutations in the Fc region.

So, if the work unexpectedly developed an antibody with a mutation in the Fc region, which is protected by a patent, then remind that, in accordance with Article 1359 of the Civil Code of the Russian Federation, there is no violation of the exclusive right to an invention in “... conducting a scientific study of a product in which the invention was used ..., or conducting an experiment on such a product ...”. Therefore, if scientists research an antibody containing a mutation under the patented invention, they cannot violate the patent.

Further, the researchers found that they obtained an antibody having remarkable properties and they decided to market it. Here remind the features of the “antibody” subject matter and the process of introduction into civil commerce.

So, in the laboratory and, moreover, in the industry, antibodies are generally obtained by genetic engineering, that is, by means of cells with specially introduced genes encoding the antibody. Thus, a developer always knows the complete information about the own antibody, including its amino acid sequence. In the case of a spontaneous mutation, which the developer has not even thought about, already in the course of production, this information will be provided by those responsible for the product quality control, which usually exist in production.

Remind that patent purity is generally checked for a product to be introduced into the civil commerce. For a comprehensive analysis of an antibody, the developer needs to know the complete sequence, which can be easily determined due to available analysis of the protein primary structure. Thus, there is virtually no chance for an unconscious introduction into civil commerce of an antibody containing a mutation according to the patented invention.

Proposals on changing regulatory requirements

Though the existing regulatory documents of the Russian Federation seem to be satisfactory, in practice, adherents of the standardized characterization of inventions in the claims treat their individual terms as prescribing the obligatory indication of the complete amino acid sequences or CDR sequences of antibodies in the claims. Thus, taking into account the aforementioned economic aspects, the positions of the developers of pioneering and most socially interesting inventions in the field of antibodies are vulnerable. Therefore, we would like to propose the following changes that would strengthen the position of developers.

To set forth clause 53(13) of the Requirements as follows: “the claims characterizing a nucleic acid, protein, polypeptide or peptide, ..., shall include the substance title, purpose-defining biological function (type of activity, biological property), unless apparently following from the title, and, if necessary, other features that allow to distinguish this compound from others, in particular, number of the corresponding nucleotide or amino acid sequence (if identified), basic structure and modifications made to the sequence of nucleotides or amino acids, presence of certain polynucleotides or amino acid sites and functional features or other characteristics thereof”.

To set forth clause 53(20) of the Requirements as follows: “the claims relating to a protein structure, where one or more components are polypeptides, should include its title specifying the purpose or defining the biological function, and features that characterize the structural implementation”.

Conclusions

Considering that technical progress entails the creation of new objects, as well as changes to existing objects that could not be imagined before, the possibilities for characterizing the invention in the claims should only expand to keep pace with this progress. Therefore, it is necessary not only not to reduce the variants characterizing antibodies in the claims, but, on the contrary, to look for and propose new approaches to characterizing antibodies in view of the state of art and prospects of development in biotechnology, and appropriately supplement the regulatory documents and comments thereto

References

1. Gavrilova E. B. and Babakova T. S. // Characterization of antibodies as a technical solution // Patents and Licenses. Intellectual Rights (Patenty i litsenzii. Intellektual'nyye prava), 2018, no. 9 (in Russian).

2. Mikhailov A.V. // Involuntary Use of Inventions in the field of Pharmaceuticals // Journal of the Court for Intellectual Property Rights (Zhurnal suda po intellektual'nym pravam), 2017, March, June (in Russian).

3. Review of Trends in the Global and Russian Pharmaceutical Market prepared by Frost & Sullivan International Consulting Company together with the Market of Innovations and Investments of the Moscow Exchange and the Industry Development Fund // https://fs.moex.com/files/14283 (in Russian).

4. Antibody sequencing service // https://www.genscript.com/mAb-sequencing.html.

5. Collier R. // Drug patents the evergreening problem. CMAJ//https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680578/.

6. Germinario C. et al. // Patentability of antibodies for therapeutic use in Europe // Nature biotechnology, 2018.

7. J. A. Kemp // Briefing Antibodies in the European patent Office – Basic principles // https://www.jakemp.com/en/knowledge-centre/briefings/antibodies-in-the-european-patent-office-basic-principles.

8. Köhler G. & Milstein C. // Continuous cultures of fused cells secreting antibody of predefined specificity // Nature.

9. Llewelyn M. B., H.R. // Discovery of antibodies. 1992.

10. Research Antibodies Market Size, Share & Trends Analysis Report By Product, By Type (Monoclonal, Polyclonal), By Technology, By Source, By Application (Oncology, Neurobiology), By End-use, And Segment Forecasts, 2018–2025, Mar, 2018 // https://www.grandviewresearch.com/industry-analysis/research-antibodies-market.

11. Storz U. // IP Issues of Therapeutic Antibodies” Intellectual property issues, Springerbriefs in Biotech patents // https://www.springer.com/.../9783642295256-c1.pdf.

12. The Nobel Prize in Physiology or Medicine 1972 // https://www.nobelprize.org/prizes/medicine/1972/summary/.

13. Umbrella patent // https://www.merriam-webster.com/dictionary/umbrella%20patent.

14. Williams A.F. et al // Analysis of cell surfaces by Xenogenic myeloma-hybrid antibodies: Differentiation antigens of rat lymphocytes. 1977.

Footnotes

1. Gavrilova E. B. and Babakova T. S. // Characterization of antibodies as a technical solution // Patents and Licenses. Intellectual Rights (Patenty i litsenzii. Intellektual'nyye prava), 2018, no. 9 (in Russian).

2. Llewelyn M. B., H.R. // Discovery of antibodies. 1992

3. The Nobel Prize in Physiology or Medicine 1972//https://www.nobelprize.org/prizes/medicine/1972/summary/

4. Köhler G. & Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature.

5. Research Antibodies Market Size, Share & Trends Analysis Report By Product, By Type (Monoclonal, Polyclonal), By Technology, By Source, By Application (Oncology, Neurobiology), By End-use, And Segment Forecasts, 2018–2025, Mar, 2018//https://www.grandviewresearch.com/industry-analysis/research-antibodies-market

6. Review of Trends in the Global and Russian Pharmaceutical Market prepared by Frost & Sullivan International Consulting Company together with the Market of Innovations and Investments of the Moscow Exchange and the Industry Development Fund // https://fs.moex.com/files/14283 (in Russian).

7. Ibid.

8. Antibody sequencing service // https://www.genscript.com/mAb-sequencing.html.

9. Similar solutions can be found in so-called “Hamers patent family”.

10. Germinario C. et al. // Patentability of antibodies for therapeutic use in Europe // Nature biotechnology, 2018; J. A. Kemp // Briefing Antibodies in the European patent Office – Basic principles//https://www.jakemp.com/en/knowledge-centre/briefings/antibodies-in-the-european-patent-office-basic-principles; Storz U. // IP Issues of Therapeutic Antibodies Intellectual property issues, Springerbriefs in Biotech patents // https://www.springer.com/.../9783642295256-c1.pdf.

11. Biological Encyclopedic Dictionary. 2-nd ed., corrected. Moscow: Soviet Encyclopedia, 1986 (in Russian).

12. https://www.lgcstandards-atcc.org/search#q=product%20format&sort=relevancy

13. Gavrilova E. B. and Babakova T. S. // Characterization of antibodies as a technical solution // Patents and Licenses. Intellectual Rights (Patenty i litsenzii. Intellektual'nyye prava), 2018, no. 9 (in Russian).

14. Research Antibodies Market Size, Share & Trends Analysis Report By Product, By Type (Monoclonal, Polyclonal), By Technology, By Source, By Application (Oncology, Neurobiology), By End-use, And Segment Forecasts, 2018–2025, Mar, 2018 // https://www.grandviewresearch.com/industry-analysis/research-antibodies-market.

15. Umbrella patent//https://www.merriam-webster.com/dictionary/umbrella%20patent.

16. Collier R. Drug patents the evergreening problem. CMAJ // https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680578/.

17. Gavrilova E. B. and Babakova T. S. // Ibid.