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Third Party Opposition against Sanofi’s Patent Application no. BR 11 2015 001145-4 (Sanofi 1)

Sanofi seeks to perpetuate an undue protection in the field of vaccination against Dengue.

Prior Art Listing

Sanofi 1 (Patent Application no. BR 11 2015 001145-4)

Patent Application no. BR 11 2015 001145-4 does not merit being granted, as it is contrary to many of the legal requirements set forth on Public Law no. 9.729/96 (Industrial Property Statute – LPI)

Unpatentability of Therapeutic Methods

Art. 10, VIII, of the LPI

Insufficiency of Disclosure

Art. 24 of the LPI

Lack of Clarity and Support of the Claims

Art. 25 of the LPI

Lack of Novelty

Art. 8º and 11 of the LPI

Lack of an Inventive Step

Art. 8º and 13 of the LPI

Sanofi 1 – Unpatentability of Therapeutic Methods

The current claims of the Sanofi 1 application clearly attempt to protect therapeutic methods – which is in explicit violation of the Industrial Property Statute

• Industrial Property Statute (LPI)

  Article 10 – The following are not considered to be inventions or utility models: […]
  VIII – operating or surgical techniques and therapeutic or diagnostic methods, for use on the human or animal body; […]

• BRPTO’s Resolution no. 169/2016

  1.27 – Therapeutic methods are those that imply the cure and/or the prevention of a disease or disorder of the human or animal body, or the relief of symptoms of pain, suffering and discomfort, for the purpose of reestablishing or maintaining the normal health conditions thereof.

• Text of Claim 1

  “A vaccine composition, characterized in that it is for use in a method of protecting a human subject against dengue disease […] wherein said method comprises administering said composition in a first dose, a second dose and a third dose and wherein said second dose is to be administered six months after said first dose and wherein said third dose is to be administered twelve months after said first dose and wherein said doses are administered via a subcutaneous route.”

• Text of Claim 20

  A kit characterized in that it comprises a composition as defined in any one of claims 1 to XX and instructions for the use of said composition, for a method of protecting a human subject against dengue disease.
  .

• Text of Claim 21

  Use of an effective amount of a composition as defined in any one of claims 1 to XX, characterized in that it is in the preparation of a composition for protecting a human subject against dengue disease.

Sanofi 1 – Insufficiency of Disclosure

The current claims of the Sanofi 1 application cover subject matter which is not supported by the specification. Thus, the Person of Ordinary Skill in the Art (POSITA) has no means of reproducing the technology without incurring in undue experimentation.

• Industrial Property Statute (LPI)

  Article 24 – The specification must describe the subject matter clearly and sufficiently so as to enable a person skilled in the art to carry it out and to indicate, when applicable, the best mode of execution.

• BRPTO’s Resolution no. 169/2016

  2.13 The descriptive sufficiency must be assessed based on the specification, which must disclose the invention in a sufficiently clear and precise manner so as to be reproduced by a person skilled in the art. The specification must contain enough conditions that ensure the achievement of the claimed invention.

  2.15. In this context, it must be ensured that the application contains sufficient technical information to enable a person skilled in the art to:
  put the invention as claimed into practice, without undue experimentation, and
  understand the contribution of the invention to the state of the art to which it belongs.
  By undue experimentation it is understood when a person skilled in the art, from the disclosed in the invention, requires additional experimentation to carry it out.

What is actually disclosed in the specification?

Example 1

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Example 2

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Example 3

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Example 4

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What is claimed yet not disclosed in the specification?

The claim allows for the inclusion of all types of viruses

While the specification only discloses the ChimeriVax concept – a chimeric virus formed using a Yellow Fever backbone (YF17D) – the claims encompass several types of viruses which could be used in a vaccine for eventually eliciting an immune response against dengue (even those not yet produced or tested). This wide array of claimed subject matter is simply not supported in any way by the scope of the disclosure.

Sanofi 1 – Lack of Clarity and Support of the Claims

• Industrial Property Statute (LPI)

  Article 25 – The claims must be based on the specification, characterizing the particularities of the application and defining clearly and precisely the subject matter to be protected.

• BRPTO’s Resolution no. 124/2013

  3.85. Article 25 of the IPL sets forth that the claims must be based on the specification, characterizing the particularities of the application and clearly and precisely defining the subject matter to be protected. This means that there must be a basis in the specification for the subject matter of every claim and the scope of the claims must not be broader than the content of the specification and drawings, if any, and based on the contribution to the state of the art.

  3.86. The proper formulation of a claim must meet the requirement of precision established in Article 25 of the IPL. Most claims are generalizations from one or more particular examples. The extent of generalization permissible is a matter that the examiner must analyze in each particular case in the light of the relevant state of the art.

• BRPTO’s Resolution no. 169/2016

  7.7 Qualitative and/or quantitative definitions, with greater of lesser degree of precision, will only need to be present when they are indispensable to clarity and precision of the claim.
  Compositions exclusively defined by the use, form of administration or mechanism of action thereof

  7.8 Claims of this type are not precise, causing a lack of definition as to the protected subject matter, and should be rejected as set forth in the provisions of article 25 of the IP Statute.

BRPTO’s Resolution no. 208/2017 – Guidelines for Patent Applications in the Field of Chemistry

Composition claims related to a therapeutic regimen cannot be accepted as they lack clarity

6. COMPOSITIONS, FORMULATIONS AND PHYSICAL FORMS OF COMPOSITIONS

6.1. CLARITY AND PRECISENESS OF CLAIMS

Example 11:

Claim 1: Pharmaceutical composition, characterized by comprising compound A and excipients B and C.

Claim 2: Pharmaceutical composition according to claim 1, characterized by the fact that the dosage of A varies from 45 to 90 mg per Kg of the patient.

Not acceptable for lacking clarity (Article 25 of the IPL) since the additional feature of the dependent claim refers to the method of administration of the pharmaceutical composition, which is part of the therapeutic regimen, and is not related to the product. The added characteristic does not add information regarding the product per se, thereby generating inconsistency as to the claimed subject matter.

Claim 3: Pharmaceutical composition according to claim 1, characterized by the fact of being administered 2 times a day.

Not acceptable for lacking clarity (Article 25 of the IPL), since the additional feature of the dependent claim refers to the method of administration of the pharmaceutical composition, which is part of the therapeutic regimen, and is not part of the product. The added characteristic does not add information regarding the product per se, thereby generating inconsistency as to the claimed subject matter.

“Use” claims with features related to a therapeutic regimen cannot be accepted for lack of clarity

9. NOVEL USES OF KNOWN COMPOUNDS

9.1.4. Groundings, clarity and preciseness of the claims

The claims of new use for preparing a medicament should specify the disease to be treated. […]

Fragments related to the therapeutic regimen contained within the new medical use claims and the group of patients neither define the use of the compound for preparing a medicament, and as such, they cannot be accepted for causing uncertainty as to the subject matter.

In this sense, it is clear that the claims of Sanofi 1 lack clarity, whereas:

Claim 1 is a composition claim linked to a therapeutic regimen,

and, thus, is not patentable according to art. 25 of the LPI and item 6.1 of the BRPTO’s Resolution no. 208/2017

Claim 1 lacks disclosure and support,

because the dengue antigens are not clearly defined in the claim as their nucleotide sequences are not being precisely recited
and, thus, is not patentable according to art. 25 of the LPI

Claim 1 is imprecise,

because the characteristics related to the choice of a certain group of patients in a composition claim is not precise and, thus, is not patentable according to art. 25 of the LPI

Claim 20 is a kit comprising the matter of Claim 1

and, thus, is not patentable according to art. 25 of the LPI and item 6.1 of the BRPTO’s Resolution no. 208/2017

Claim 21 is an “use” claim linked to a therapeutic regimen

and, thus, is not patentable according to art. 25 of the LPI and item 9.1.4 of the BRPTO’s Resolution no. 208/2017

Sanofi 1 – Patentability

Relevant Prior Art Documents

D1 – WO2003101397

Date of Publishing: 11/12/2003

Published as: WIPO International Patent Application

Main Disclosures:
• Tetravalent Dengue Vaccines which induces immunty against all four Dengue Virus serotypes (DEN 1-4)
• Describes the development of CYD, i.e., chimeric yellow fever/dengue (CYD) constructs comprising a yellow fever backbone, in which the pre-membrane (prM) and envelope (E) genes of wild-type dengue viruses are inserted. For each dengue serotype, a chimera was generated (CYD1-4, also referred to as ChimerivaxTM dengue serotype 1-4) for application in the tetravalent vaccine composition
• The wild type dengue viruses from which the chimeric viruses have been derived are the same as of the ones disclosed in Example 1 of application BR112015001145-4.

D2 – Guy et al.

Date of Publishing: 01/09/2010

Published as: Scientific Article in the “Human Vaccines” journal, v. 6, issue 9, p. 696-705.

Main Disclosures:
• The review is concerned about developments made in relation to Sanofi Pasteur tetravalent vaccine candidate composed of four recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes, also known as Chimerivax.
• The paper discusses about the overall development of the CYD 1-4 viruses used in the relevant vaccine, i.e., the chimeric yellow fever/dengue (CYD) constructs (see Figure 1); and comments about the Pre-clinical evaluation and Clinical Development of the vaccine, at the occasion.
• Phase I studies with monovalent CYD-2 and Tetravalent (TDV) vaccine have been discussed in this Review, with seroconversion of volunteers being shown, inclusive for all four serotypes with TDV.
• Phase IIb and Phase III clinical evaluations being conducted are mentioned in the paper, thus showing that efficacy tests were being carried out with the vaccine. Particularly, the Phase IIb Trial being conducted in Thailand (endemic area) with children aged 4-11 years, which results are described in application BR112015001145-4 (Example 1), are reported in this paper.
• The document, therefore, discloses the immunogenicity achieved with the TDV vaccine, the use of the vaccine in humans (children from endemic areas), and the dosage regimen of 0-6-12 months.

D3 – Study NCT01373281, CYD, sponsored by Sanofi

Date of Publishing: 14/06/2011

Published as: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

Main Disclosures:
• The clinical trial is a Phase III study with CYD-TDV (or Chimerivax) vaccine, in particular a clinical trial concerned with efficacy of the CYD-TDV vaccine in preventing symptomatic, virologically confirmed dengue cases due to any of the four Dengue Virus serotype.
• The CYD-TDV dengue vaccine is applied to children aged 2 to 14 years.
• The vaccination regimen corresponds to 3 vaccinations at 0, 6 and 12 months.
• This document corroborates the vaccination regimen described in Guy et al., 2010 and in Example 1 from application BR112015001145-4.
• This study is commented by Capeding et al., 2014, Lancet 384:1358-65

D4 – Study NCT01374516, CYD, sponsored by Sanofi

Date of Publishing: 16/06/2011

Published as: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Main Disclosures:
• The clinical trial is directed to a Phase III study regarding the vaccine TDV-CYD, in particular, like D4, to a clinical trial concerned with efficacy (conference of protection) of the TDV-CYD vaccine against dengue disease.
• The CYD dengue vaccine is applied to children aged 9 to 16 years in Latin America.
• The vaccination regimen corresponds to 3 vaccinations at 0, 6 and 12 months.
• This document corroborates the vaccination regimen described in Guy et al., 2010 and in Example 1 from application BR112015001145-4.
• This study is commented by Villar et al., 2015, N Engl J Med 372:113-23

D5 – WO2006134443 – DENGUE SEROTYPE 2 ATTENUATED STRAIN

Date of Publishing: 21/12/2006

Published as: WIPO International Patent Application

Main Disclosures:
• The application discloses a live attenuated VDV2 strain derived from dengue 2 strain PDK53-16681 (also known as LAV-2). The tetravalent vaccine VDV-2/CYD-1,3,4 is also foreseen in the document.
• VDV2 amino acid and nucleotide sequences, also compared to PDK53-16681, are revealed in the application (below).
• The full sequence of VDV-2 is disclosed as SEQ ID NO: 1 in this application.
• The tetravalent vaccine VDV-2/CYD-1,3,4 was object of a Phase II Clinical Trial registered with number NCT00740155 (first posted on August 22, 2008) to provide safety information concerning the tested bivalent and tetravalent formulations.
• Health Naïve Volunteers aged 18 to 45 years participated from this study.

D6 – Osorio et al.

Date of Publishing: 21/07/2011

Published as: Scientific Article in the “Vaccine” journal, v. 29, issue 42, p. 7251-7260.

Main Disclosures:
• This document consists of a review article disclosing the results of a chimeric dengue-2 PDK-53-based tetravalent vaccine successfully protecting monkeys in challenge studies. PDK-53 strain is also known as LAV-2, the same serotype 2 strain disclosed in Examples 2 and 3 from application BR112015001145-4, from which VDV-2 strain, employed in Example 4 has been attenuated.
• The paper describes the attenuated DEN-2 PDK-53 strain and chimeric viruses containing the prM and E genes from DEN-1, DEN-3 and DEN-4, in a DEN-2 PDK-53 backbone, known as DENVax.
• The tetravalent vaccine candidate showed a safety profile and immunogenicity against the four Dengue serotypes, as shown in Phase I Clinical Trials.
• This document anticipates the use of the serotype-2 Dengue virus strain LAV-2 (PDK-53), both in the attenuated form and in the chimeric form.

D7 – Bhamarapravati & Sutee

Date of Publishing: 28/03/2000; Date of Publishing (online): 01/09/2010

Published as: Scientific article in the “Vaccine” journal, v. 18, p. 44-47.

Main Disclosures:
• Bhamarapravati is a short communication reporting the developments of dengue vaccines, at the Mahidol University group based on live attenuated (non-chimeric) dengue viruses obtained by serial passages of the viruses in primary dog kidney cells or primary African green monkey kidney cells.
• According to the authors, tetravalent vaccines described have been tested in Thai volunteers, and were found to be immunogenic in both adults and children.
• This document is relevant with regard to the broad component “live attenuated dengue virus” from currently pending claim 1.

Sanofi 1 – Patentability

Lack of Novelty and an Inventive Step

• Industrial Property Statute (LPI)

  Article 8 – To be patentable an invention must meet the requirements of novelty, inventive activity and industrial application

  Article 11 – Inventions and utility models are considered to be new when not included in the state of the art.

  Article 13 – An invention shall be taken to involve inventive activity when, for a person skilled in the art, it does not derive in an evident or obvious manner from the state of the art.

• BRPTO’s Resolution no. 169/2016

  7.5 – The compositions not comprised in the prior art are deemed novel. The composition containing component(s) that are already known in the prior art will be deemed novel if it has features, such as, other components and ratio between components, to distinguish it from the state of the art.

  7.6 – The effect, use or the mode of administration/release per se do not confer novelty to a composition that is known in the art. However, these elements can be accepted in the text of the claims to provide clarity and precision to the claimed subject matter.
  Example: A “pharmaceutical composition characterized by containing X and Y” lacks novelty over a prior art document referring to a detergent composition characterized by containing X and Y.

• BRPTO’s Resolution no. 208/2017

  9.1. NEW MEDICAL USE
  9.1.1 Novelty
  a disease which is different from that for which the product is employed In order to be considered novel, the new medical use invention must disclose the application of a pharmaceutical product already known in the art for producing a medicament for treating or preventing in the state of the art.
  Features related to the use of the compound, such as therapeutic regimen (dosage, administration mode/ application, dosage interval) and/ or group of patients do not render the use of a known compound novel. For example, if the state of the art discloses the “use of compound X for manufacturing a medicament for treating disease Y” and the application seeks protection for the “use of compound X for manufacturing a medicament for treating disease Y for treating diabetic patients”, the claimed use is not considered novel.

Sanofi 1 lacks novelty when compared to D1

The standard Lorem Ipsum passage, used since the 1500s

Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of “de Finibus Bonorum et Malorum” (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, “Lorem ipsum dolor sit amet..”, comes from a line in section 1.10.32.

Sanofi 1 lacks novelty when compared to D2

The standard Lorem Ipsum passage, used since the 1500s

Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of “de Finibus Bonorum et Malorum” (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, “Lorem ipsum dolor sit amet..”, comes from a line in section 1.10.32.

Sanofi 1 – Opinions from Experts in the Field

Renowned experts from the field of immunology attest and reinforce that the Sanofi 1 application DOES NOT meet the requirements for patentability as set forth in the Industrial Property Statute (Public Law no. 9.279/96) and the BRPTO’s Guidelines for Patent Applications (specifically Resolutions no. 169/2016 and 208/2017).

Aliquam dignissim lacinia tristique nulla lobortis nunc ac eros scelerisque varius suspendisse sit amet urna vitae urna semper quis at ligula.
Dr.ª Alice RayolFarmacêutica, Imunóloga e Doutora em Propriedade Intelectual

Aliquam dignissim lacinia tristique nulla lobortis nunc ac eros scelerisque varius suspendisse sit amet urna vitae urna semper quis at ligula.
Dr.ª Ana Claudia Dias de OliveiraBióloga e Doutora em Biotecnologia e Propriedade Intelectual

Sanofi 1 – Takeaways

Due to its lack of conformity with the legal standards for patentability, the Sanofi 1 application should be rejected by the National Institute of Industrial Property (INPI – BRPTO).

Unpatentability of Therapeutic Methods

Art. 10, VIII, of the LPI

Insufficiency of Disclosure

Art. 24 of the LPI

Lack of Clarity and Support of the Claims​

Art. 25 of the LPI

Lack of Novelty

Art. 8º and 13 of the LPI

Lack of an Inventive Step

Art. 8º and 13 of the LPI

Scenario 2

Sanofi 1 (Patent Application no. BR 11 2015 001145-4)

Patent Application no. BR 11 2015 001145-4 does not merit being granted, as it is contrary to many of the legal requirements set forth on Public Law no. 9.729/96 (Industrial Property Statute – LPI)

Unpatentability of Therapeutic Methods

Art. 10, VIII, of the LPI

Insufficiency of Disclosure

Art. 24 of the LPI

Lack of Clarity and Support of the Claims

Art. 25 of the LPI

Lack of Novelty

Art. 8º and 11 of the LPI

Lack of an Inventive Step

Art. 8º and 13 of the LPI

Sanofi 1 – Unpatentability of Therapeutic Methods

The current claims of the Sanofi 1 application clearly attempt to protect therapeutic methods – which is in explicit violation of the Industrial Property Statute

• Industrial Property Statute (LPI)

  Article 10 – The following are not considered to be inventions or utility models: […]
  VIII – operating or surgical techniques and therapeutic or diagnostic methods, for use on the human or animal body; […]

• BRPTO’s Resolution no. 169/2016

  1.27 – Therapeutic methods are those that imply the cure and/or the prevention of a disease or disorder of the human or animal body, or the relief of symptoms of pain, suffering and discomfort, for the purpose of reestablishing or maintaining the normal health conditions thereof.

• Text of Claim 1

  “1. A vaccine composition, characterized by the fact that it is for use in a method of protecting a human individual who is 9-45 years of age and is resident in a dengue endemic area against dengue disease caused by dengue virus of any type of serotypes 1 to 4, wherein said composition comprises a dengue antigen of serotype 1, a dengue antigen of serotype 2, a dengue antigen of serotype 3 and a dengue antigen of serotype 4,
  wherein said dengue antigens of serotypes 1, 3 and 4 are each a live attenuated chimeric dengue virus, and wherein said live attenuated chimeric dengue virus is a recipient flavivirus in which the gene sequence has been modified by exchanging the sequences encoding the prM and E proteins of the recipient flavivirus by the corresponding sequences of a dengue virus;
  wherein said recipient flavivirus is selected from a yellow fever virus and a dengue virus;
  wherein said dengue antigen of serotype 2 is
  a live attenuated dengue virus which comprises a nucleic acid sequence as set forth in SEQ ID NO: 24 or
  a live attenuated dengue virus which comprises a nucleic acid sequence having at least one and no more than 20 nucleotide substitutions when compared with the sequence as set forth in SEQ ID NO: 24 and comprises the E protein sequence selected from SEQ ID NO: 13 and SEQ ID NO: 26 and the M protein sequence selected from SEQ ID NO: 19 and SEQ ID NO: 27;
  and wherein the method results in a statistically significant reduction in the likelihood of the dengue disease caused by dengue virus of any one of serotypes 1 to 4.”

Sanofi 1 – Insufficiency of Disclosure

The current claims of the Sanofi 1 application cover subject matter which is not supported by the specification. Thus, the Person of Ordinary Skill in the Art (POSITA) has no means of reproducing the technology without incurring in undue experimentation.

• Industrial Property Statute (LPI)

  Article 24 – The specification must describe the subject matter clearly and sufficiently so as to enable a person skilled in the art to carry it out and to indicate, when applicable, the best mode of execution.

• BRPTO’s Resolution no. 169/2016

  2.13 The descriptive sufficiency must be assessed based on the specification, which must disclose the invention in a sufficiently clear and precise manner so as to be reproduced by a person skilled in the art. The specification must contain enough conditions that ensure the achievement of the claimed invention.

  2.15. In this context, it must be ensured that the application contains sufficient technical information to enable a person skilled in the art to:
  put the invention as claimed into practice, without undue experimentation, and
  understand the contribution of the invention to the state of the art to which it belongs.
  By undue experimentation it is understood when a person skilled in the art, from the disclosed in the invention, requires additional experimentation to carry it out.

What is actually disclosed in the specification?

Example 1

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Example 2

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Example 3

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Example 4

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What is claimed yet not disclosed in the specification?

The claim allows for the inclusion of all types of viruses

While the specification only discloses the ChimeriVax concept – a chimeric virus formed using a Yellow Fever backbone (YF17D) – the claims encompass several types of viruses which could be used in a vaccine for eventually eliciting an immune response against dengue (even those not yet produced or tested). This wide array of claimed subject matter is simply not supported in any way by the scope of the disclosure.

Sanofi 1 – Lack of Clarity and Support of the Claims

• Industrial Property Statute (LPI)

  Article 25 – The claims must be based on the specification, characterizing the particularities of the application and defining clearly and precisely the subject matter to be protected.

• BRPTO’s Resolution no. 124/2013

  3.85. Article 25 of the IPL sets forth that the claims must be based on the specification, characterizing the particularities of the application and clearly and precisely defining the subject matter to be protected. This means that there must be a basis in the specification for the subject matter of every claim and the scope of the claims must not be broader than the content of the specification and drawings, if any, and based on the contribution to the state of the art.

  3.86. The proper formulation of a claim must meet the requirement of precision established in Article 25 of the IPL. Most claims are generalizations from one or more particular examples. The extent of generalization permissible is a matter that the examiner must analyze in each particular case in the light of the relevant state of the art.

• BRPTO’s Resolution no. 169/2016

  7.7 Qualitative and/or quantitative definitions, with greater of lesser degree of precision, will only need to be present when they are indispensable to clarity and precision of the claim.
  Compositions exclusively defined by the use, form of administration or mechanism of action thereof

  7.8 Claims of this type are not precise, causing a lack of definition as to the protected subject matter, and should be rejected as set forth in the provisions of article 25 of the IP Statute.

BRPTO’s Resolution no. 208/2017 – Guidelines for Patent Applications in the Field of Chemistry

Composition claims related to a therapeutic regimen cannot be accepted as they lack clarity

6. COMPOSITIONS, FORMULATIONS AND PHYSICAL FORMS OF COMPOSITIONS

6.1. CLARITY AND PRECISENESS OF CLAIMS

Example 11:

Claim 1: Pharmaceutical composition, characterized by comprising compound A and excipients B and C.

Claim 2: Pharmaceutical composition according to claim 1, characterized by the fact that the dosage of A varies from 45 to 90 mg per Kg of the patient.

Not acceptable for lacking clarity (Article 25 of the IPL) since the additional feature of the dependent claim refers to the method of administration of the pharmaceutical composition, which is part of the therapeutic regimen, and is not related to the product. The added characteristic does not add information regarding the product per se, thereby generating inconsistency as to the claimed subject matter.

Claim 3: Pharmaceutical composition according to claim 1, characterized by the fact of being administered 2 times a day.

Not acceptable for lacking clarity (Article 25 of the IPL), since the additional feature of the dependent claim refers to the method of administration of the pharmaceutical composition, which is part of the therapeutic regimen, and is not part of the product. The added characteristic does not add information regarding the product per se, thereby generating inconsistency as to the claimed subject matter.

“Use” claims with features related to a therapeutic regimen cannot be accepted for lack of clarity

9. NOVEL USES OF KNOWN COMPOUNDS

9.1.4. Groundings, clarity and preciseness of the claims

The claims of new use for preparing a medicament should specify the disease to be treated. […]

Fragments related to the therapeutic regimen contained within the new medical use claims and the group of patients neither define the use of the compound for preparing a medicament, and as such, they cannot be accepted for causing uncertainty as to the subject matter.

In this sense, it is clear that the claims of Sanofi 1 lack clarity, whereas:

Claim 1 is imprecise,

because the characteristics related to the choice of a certain group of patients in a composition claim is not precise and, thus, is not patentable according to art. 25 of the LPI

Claim 1 lacks disclosure and support,

because the dengue antigens from serotypes 1, 3 and 4 are not clearly defined in the claim, as their nucleotide sequences are not being precisely recited and, thus, is not patentable according to art. 25 of the LPI

Claim 1’s language should not be accepted for being imprecise,

as it could encompass numerous nucleotide sequences that are not supported by the description of the specification and, thus, is not patentable according to art. 25 of the LPI

Claim 1 isn’t considered clear and precise,

because, as a composition claim, it has features related to the results and, thus, is not patentable according to art. 25 of the LPI

Sanofi 1 – Patentability

Relevant Prior Art Documents

D1 – WO2003101397

Date of Publishing: 11/12/2003

Published as: WIPO International Patent Application

Main Disclosures:
• Tetravalent Dengue Vaccines which induces immunty against all four Dengue Virus serotypes (DEN 1-4)
• Describes the development of CYD, i.e., chimeric yellow fever/dengue (CYD) constructs comprising a yellow fever backbone, in which the pre-membrane (prM) and envelope (E) genes of wild-type dengue viruses are inserted. For each dengue serotype, a chimera was generated (CYD1-4, also referred to as ChimerivaxTM dengue serotype 1-4) for application in the tetravalent vaccine composition
• The wild type dengue viruses from which the chimeric viruses have been derived are the same as of the ones disclosed in Example 1 of application BR112015001145-4.

D2 – Guy et al.

Date of Publishing: 01/09/2010

Published as: Scientific Article in the “Human Vaccines” journal, v. 6, issue 9, p. 696-705.

Main Disclosures:
• The review is concerned about developments made in relation to Sanofi Pasteur tetravalent vaccine candidate composed of four recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes, also known as Chimerivax.
• The paper discusses about the overall development of the CYD 1-4 viruses used in the relevant vaccine, i.e., the chimeric yellow fever/dengue (CYD) constructs (see Figure 1); and comments about the Pre-clinical evaluation and Clinical Development of the vaccine, at the occasion.
• Phase I studies with monovalent CYD-2 and Tetravalent (TDV) vaccine have been discussed in this Review, with seroconversion of volunteers being shown, inclusive for all four serotypes with TDV.
• Phase IIb and Phase III clinical evaluations being conducted are mentioned in the paper, thus showing that efficacy tests were being carried out with the vaccine. Particularly, the Phase IIb Trial being conducted in Thailand (endemic area) with children aged 4-11 years, which results are described in application BR112015001145-4 (Example 1), are reported in this paper.
• The document, therefore, discloses the immunogenicity achieved with the TDV vaccine, the use of the vaccine in humans (children from endemic areas), and the dosage regimen of 0-6-12 months.

D3 – Study NCT01373281, CYD, sponsored by Sanofi

Date of Publishing: 14/06/2011

Published as: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

Main Disclosures:
• The clinical trial is a Phase III study with CYD-TDV (or Chimerivax) vaccine, in particular a clinical trial concerned with efficacy of the CYD-TDV vaccine in preventing symptomatic, virologically confirmed dengue cases due to any of the four Dengue Virus serotype.
• The CYD-TDV dengue vaccine is applied to children aged 2 to 14 years.
• The vaccination regimen corresponds to 3 vaccinations at 0, 6 and 12 months.
• This document corroborates the vaccination regimen described in Guy et al., 2010 and in Example 1 from application BR112015001145-4.
• This study is commented by Capeding et al., 2014, Lancet 384:1358-65

D4 – Study NCT01374516, CYD, sponsored by Sanofi

Date of Publishing: 16/06/2011

Published as: Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Main Disclosures:
• The clinical trial is directed to a Phase III study regarding the vaccine TDV-CYD, in particular, like D4, to a clinical trial concerned with efficacy (conference of protection) of the TDV-CYD vaccine against dengue disease.
• The CYD dengue vaccine is applied to children aged 9 to 16 years in Latin America.
• The vaccination regimen corresponds to 3 vaccinations at 0, 6 and 12 months.
• This document corroborates the vaccination regimen described in Guy et al., 2010 and in Example 1 from application BR112015001145-4.
• This study is commented by Villar et al., 2015, N Engl J Med 372:113-23

D5 – WO2006134443 – DENGUE SEROTYPE 2 ATTENUATED STRAIN

Date of Publishing: 21/12/2006

Published as: WIPO International Patent Application

Main Disclosures:
• The application discloses a live attenuated VDV2 strain derived from dengue 2 strain PDK53-16681 (also known as LAV-2). The tetravalent vaccine VDV-2/CYD-1,3,4 is also foreseen in the document.
• VDV2 amino acid and nucleotide sequences, also compared to PDK53-16681, are revealed in the application (below).
• The full sequence of VDV-2 is disclosed as SEQ ID NO: 1 in this application.
• The tetravalent vaccine VDV-2/CYD-1,3,4 was object of a Phase II Clinical Trial registered with number NCT00740155 (first posted on August 22, 2008) to provide safety information concerning the tested bivalent and tetravalent formulations.
• Health Naïve Volunteers aged 18 to 45 years participated from this study.

D6 – Osorio et al.

Date of Publishing: 21/07/2011

Published as: Scientific Article in the “Vaccine” journal, v. 29, issue 42, p. 7251-7260.

Main Disclosures:
• This document consists of a review article disclosing the results of a chimeric dengue-2 PDK-53-based tetravalent vaccine successfully protecting monkeys in challenge studies. PDK-53 strain is also known as LAV-2, the same serotype 2 strain disclosed in Examples 2 and 3 from application BR112015001145-4, from which VDV-2 strain, employed in Example 4 has been attenuated.
• The paper describes the attenuated DEN-2 PDK-53 strain and chimeric viruses containing the prM and E genes from DEN-1, DEN-3 and DEN-4, in a DEN-2 PDK-53 backbone, known as DENVax.
• The tetravalent vaccine candidate showed a safety profile and immunogenicity against the four Dengue serotypes, as shown in Phase I Clinical Trials.
• This document anticipates the use of the serotype-2 Dengue virus strain LAV-2 (PDK-53), both in the attenuated form and in the chimeric form.

D7 – Bhamarapravati & Sutee

Date of Publishing: 28/03/2000; Date of Publishing (online): 01/09/2010

Published as: Scientific article in the “Vaccine” journal, v. 18, p. 44-47.

Main Disclosures:
• Bhamarapravati is a short communication reporting the developments of dengue vaccines, at the Mahidol University group based on live attenuated (non-chimeric) dengue viruses obtained by serial passages of the viruses in primary dog kidney cells or primary African green monkey kidney cells.
• According to the authors, tetravalent vaccines described have been tested in Thai volunteers, and were found to be immunogenic in both adults and children.
• This document is relevant with regard to the broad component “live attenuated dengue virus” from currently pending claim 1.

Sanofi 1 – Patentability

Lack of Novelty and an Inventive Step

• Industrial Property Statute (LPI)

  Article 8 – To be patentable an invention must meet the requirements of novelty, inventive activity and industrial application

  Article 11 – Inventions and utility models are considered to be new when not included in the state of the art.

  Article 13 – An invention shall be taken to involve inventive activity when, for a person skilled in the art, it does not derive in an evident or obvious manner from the state of the art.

• BRPTO’s Resolution no. 169/2016

  7.5 – The compositions not comprised in the prior art are deemed novel. The composition containing component(s) that are already known in the prior art will be deemed novel if it has features, such as, other components and ratio between components, to distinguish it from the state of the art.

  7.6 – The effect, use or the mode of administration/release per se do not confer novelty to a composition that is known in the art. However, these elements can be accepted in the text of the claims to provide clarity and precision to the claimed subject matter.
  Example: A “pharmaceutical composition characterized by containing X and Y” lacks novelty over a prior art document referring to a detergent composition characterized by containing X and Y.

• BRPTO’s Resolution no. 208/2017

  9.1. NEW MEDICAL USE
  9.1.1 Novelty
  a disease which is different from that for which the product is employed In order to be considered novel, the new medical use invention must disclose the application of a pharmaceutical product already known in the art for producing a medicament for treating or preventing in the state of the art.
  Features related to the use of the compound, such as therapeutic regimen (dosage, administration mode/ application, dosage interval) and/ or group of patients do not render the use of a known compound novel. For example, if the state of the art discloses the “use of compound X for manufacturing a medicament for treating disease Y” and the application seeks protection for the “use of compound X for manufacturing a medicament for treating disease Y for treating diabetic patients”, the claimed use is not considered novel.

Sanofi 1 lacks novelty when compared to D1

The standard Lorem Ipsum passage, used since the 1500s

Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of “de Finibus Bonorum et Malorum” (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, “Lorem ipsum dolor sit amet..”, comes from a line in section 1.10.32.

Sanofi 1 lacks novelty when compared to D2

The standard Lorem Ipsum passage, used since the 1500s

Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of “de Finibus Bonorum et Malorum” (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, “Lorem ipsum dolor sit amet..”, comes from a line in section 1.10.32.

Sanofi 1 – Opinions from Experts in the Field

Renowned experts from the field of immunology attest and reinforce that the Sanofi 1 application DOES NOT meet the requirements for patentability as set forth in the Industrial Property Statute (Public Law no. 9.279/96) and the BRPTO’s Guidelines for Patent Applications (specifically Resolutions no. 169/2016 and 208/2017).

Aliquam dignissim lacinia tristique nulla lobortis nunc ac eros scelerisque varius suspendisse sit amet urna vitae urna semper quis at ligula.
Dr.ª Alice RayolFarmacêutica, Imunóloga e Doutora em Propriedade Intelectual

Aliquam dignissim lacinia tristique nulla lobortis nunc ac eros scelerisque varius suspendisse sit amet urna vitae urna semper quis at ligula.
Dr.ª Ana Claudia Dias de OliveiraBióloga e Doutora em Biotecnologia e Propriedade Intelectual

Sanofi 1 – Takeaways

Due to its lack of conformity with the legal standards for patentability, the Sanofi 1 application should be rejected by the National Institute of Industrial Property (INPI – BRPTO).

Unpatentability of Therapeutic Methods

Art. 10, VIII, of the LPI

Insufficiency of Disclosure

Art. 24 of the LPI

Lack of Clarity and Support of the Claims​

Art. 25 of the LPI

Lack of Novelty

Art. 8º and 13 of the LPI

Lack of an Inventive Step

Art. 8º and 13 of the LPI

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