K&K - NCEs - Prosecution Practices

NEW CHEMICAL ENTITIES – ASPECTS OF DRAFTING AND PROSECUTION

IN INDIA

Khurana & Khurana, Advocates & IP Attorneys Noida(New Delhi) | Mumbai | Pune | Bangalore

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Phone: +91.120.2342010, 3104849, Fax: 2342011 Website: www.iiprd.comEmail: [email protected]

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Contents1. Introduction to New Chemical Entity (NCE)

2. Patent Protection for NCE

3. Challenges with Markush Claims

4. Exemplary Case Studies for Patent Prosecution at Indian Patent Office

1. IN272676

2. IN255055

3. IN249412

5. Importance of Section 8

Khurana & Khurana, Advocates & IP Attorneys © K&K, 2016

INTRODUCTION TO NEW CHEMICAL ENTITY (NCE)

• A Chemical molecule developed in the early discovery stage which later translates into a drug product.

• NCE can be a: new compound new polymer


PATENT PROTECTION FOR NEW CHEMICAL ENTITY (NCE)

• Patentable Subject Matter: A new chemical composition or formulation

A new manufacturing process

• Markush type Claim: Usually used in chemical patents, although applicable in other fields

A “Markush claim” can be considered as a shortened formulation of a claim

Markush grouping is allowable only if all alternatives have a common property or activity AND a common structure is present


CHALLENGES WITH MARKUSH CLAIMS• The Markush claims are drafted to obtain a wide scope of

protection encompassing a large number of compounds whose properties might not have been tested, but only theoretically inferred from the equivalence with other compounds within the claim

• Quite often the Markush claims generate confusions regarding the novelty, non-obviousness and industrial applicability of a group of compounds covered within the said Markush formula

• Also, the Markush claims may invoke the questions of sufficiency and plurality of distinct group of inventions surrounding such claims


Exemplary Case Studies for Patent Prosecution at Indian

Patent Office

Khurana & Khurana, Advocates & IP Attorneys

Case Study -1 • Invention: Novel 11β-hydroxyandrosta-4-ene-3-ones

• Applicant: Sun Pharma Advanced Research Company Ltd.

• Comparative Analysis for Patents in IN, US and EP: – IN272676 (131/MUM/2006)– US8785425– EP2004667

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Indian Patent Number: IN272676• Claims:


Comparative Analysis with US Patent >>>

Comparative Analysis with EP Patent >>>

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US Patent >>>

EP Patent >>>

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Objections Raised by Examiner

• Claim 1 and therefore its dependent claims lack novelty/inventive step in view of documents:

D1: US4996335 D2: BE889563 D3: Pharmaceutical Research (1999), 16(6), 961-967

(abstract). Documents D1-D3 disclose compounds which are included in the general formulas as defined by the claims of the application. Therefore, these claims cannot be regarded as novel or inventive.


Response Submitted by Applicant• Analysis and remarks made by the applicant:

Note: D1 and D2 were family members and hence shared the disclosed subject matter.




Allowance of Claims

With these arguments and assertions accepted, the patent wasgranted on the grounds that the structural formula of thecompounds could not be anticipated by the markush formulaof the compounds disclosed in cited prior art documents andhence the subject matter covered by the instant application isnovel and involves inventive step.



US Patent Number: US8785425• Claims:

Comparative Analysis with IN Patent <<<


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EP Patent Number: EP2004667• Claims:


Comparative Analysis with US Patent <<<

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Conclusion1. From the analysis of prosecution history of IN, EP and US patents, following

references were found to be cited by the Examiner –

• It could be concluded that references cited by the examiner during prosecution of Indian Patent application matches closely to those cited during prosecution of EP application in comparison to US patent application.


IN272676 US8785425 EP2004667

- US6610675 GB2079755

US4996335 US4996335 US4996335

BE889563 US7208613 BE889563

Little et al., Pharmaceutical

Research (1999), 16(6), 961-967

US6197761 Little et al., Pharmaceutical

Research (1999), 16(6), 961-967

- US7405206 -

Conclusion2. From the analysis of allowed independent claims, it can be concluded

that the scope of the first independent claim of EP patent (EP2004667) is significantly broad when compared to their Indian (IN272676) and US (US8785425) counterparts. Following major differences could be observed-

In EP2004667 and IN272676, R1 could be hydrogen or methyl or methylene. However, in US8785425, R1 was restricted to be selected only from hydrogen or methyl.

In EP2004667, R5 could be any group selected from (C1-C10)-alkyl, (C3-C13)-cycloalkyl, -O- (C1-C10)-alkyl, aryl or heterocyclic ring and others. However, in US8785425 and IN272676, R5 was restricted to be selected from (C1-C4)-alkyl, (C3-C6)-cycloalkyl, -O- (C1-C4)-alkyl, and a phenyl ring or heterocyclic ring and others.



Case Study -2 • Invention: Fused Pyrazole Compounds As Cannabinoid

Receptor Modulators

• Applicant: Glenmark Pharmaceuticals

• Comparative Analysis for Patents in IN, US and EP: – IN255055 (2225/MUMNP/2007)– US7923465– EP1902034

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Patent Number: IN255055• Claims:




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Objections Raised by Examiner• Asserted that the subject matter in any of the claims lacks

novelty as being anticipated by D1 through D5 and hence is not patentable under section 2 (1) (j) of the Indian Patent Act.


Response Submitted by Applicant• The applicant accepted that D1-D4 disclosed the following

compounds which were relevant to the claims as originally filed.


• The applicant then amended the claims by restricting its scope.


• In the amended claims, the variable R in formula I was restricted to represent substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or

unsubstituted heteroaryl.

• But D1-D4 disclosed such compounds with a hydrogen or Amido group at the corresponding position.

• Applicant further stated that although D5 disclosed pyrazole and the use thereof as cannabinoid receptor modulators, but none of those compounds disclosed a bridged ring system condensed with the pyrazoles.

• Therefore, the grounds of objection stand moot.


Allowance of Claims

With these arguments and assertions accepted, the patent wasgranted on the grounds that the structural formula of thecompounds could not be anticipated by the formulaof the compounds disclosed in cited prior art documents andhence the subject matter covered by the instant application isnovel and involves inventive step.






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1. From the analysis of prosecution history of IN, EP and US patents, following references were found to be cited by the Examiner -


IN255055 US7923465 EP1902034NAGAI et al., Chem. Pharm. Bull.

(1979), 27(8), 1764-1770- NAGAI et al., Chem. Pharm. Bull.

(1979), 27(8), 1764-1770

EGG et al., Monatshefte Fur Chemie (1969), 100, 1256-1259

Egg et al., 1969, CAS: 71: 101768 EGG et al., Monatshefte Fur Chemie (1969), 100, 1256-1259

Database Crossfire Beilstein, Frankfurt Am Main, DE; 1982,

XP002402588

- Database Crossfire Beilstein, Frankfurt Am Main, DE; 1982,

XP002402588

WALLACH et al., Justus Liebigs Ann. Chem. (1903), 329, 109-133

- WALLACH et al., Justus Liebigs Ann. Chem. (1903), 329, 109-133

- Watson et al., 1995, CAS: 124:104533

WO0158869

- Nagai et al., 1980, CAS: 92:181074 WO0132629

- - WO0132663

- - WO2006/030124

Conclusion

Conclusion2. From the analysis of allowed independent claims, it can be concluded that the

scope of the first independent claim of EP patent (EP1902034) is significantly broad when compared to its Indian (IN255055) and US (US7923465) counterparts. Following major differences could be observed-

In EP1902034, U and V are independently C or N and W, X and Y are independently C, N, O, S or –C(O)-. However, in IN255055, U and V are restricted to C and W, X and Y are restricted to C and N. Further, in US7923465, the inner ring atoms are clearly specified as C and N.

In IN255055 and EP1902034 R1 and R2 may be joined together to form an optionally substituted 3 to 7 membered saturated or unsaturated cyclic ring. However, in US7923465 R1 and R2 may be joined together to form an optionally substituted piperidinyl ring.

In EP1902034, each occurrence of B is independently O, S or NR3. However, B is restricted only to O in US7923465 and IN255055.

Further, it could be concluded that references cited by the examiner during prosecution of Indian Patent application matches closely to those cited during prosecution of EP application in comparison to US patent application.



Case Study - 3 • Invention: Substituted Benzofused Derivatives And Their Use

As Vanilloid Receptor Ligands

• Applicant: Glenmark Pharmaceuticals

• Comparative Analysis for Patents in IN, US and EP: – IN249412 (879/MUMNP/2008) – US7842703– EP1931681

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IN249412• Claims:




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Objections Raised by ExaminerThe application lacks novelty because the subject matter of claims 1-3,5,6,8-11,13-16,18-25,27-29 is not new in view of the cited documents:

D1: WO2005/075463D2: WO00/3681 A2D3: FR-A-2661676D4: Database Chemcats Chemical Abstracts service, Colombus, Ohio, US; (2005-07-03),XP002414754D5: WO 03/080578 A (MERCK SHARP AND DOHME [GB]; BROWN REBECCA ELIZABETH[GB]; DOUGHTY VICTOR) (2003-10-02) cited in the application


• Necessary amendments were made by the applicant. The applicant renumbered claim 39 as claim 1 and amended it to specify that R1 and R2 together form a cyclobutane or fully saturated pyran as well as substituents R7 and R8 are replaced by isoquinoline moiety.

• In support of the assertion made, the applicant further stated that D1 although discloses the benzopyran derivatives containing thioureido side chain, it fails to suggest or motivate PHOSITA to prepare benzopyran derivatives containing urea substituted with isoquinoline moiety.

Response Submitted by Applicant


• He further stated that D2 discloses benzopyran derivatives with an amide substitution at 6th position whereas the instant application did not cover derivatives with such substitution.

• He asserted that D3 and D4 did not suggest or motivate PHOSITA to prepare benzopyran derivatives of urea having bicyclic ring such as isoquinoline moiety as another substituent.

• He concluded his remarks for novelty and inventive step with D5 not citing any example of benzopyran derivatives even though substituted urea derivatives are disclosed.

Response Submitted by Applicant


Allowance of Claims

With these arguments and assertions accepted, the patent wasgranted on the grounds that the structural formula of thecompounds could not be anticipated by the formulaof the compounds disclosed in cited prior art documents andhence the subject matter covered by the instant application isnovel and involves inventive step.






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Conclusion1. From the analysis of prosecution history of IN, EP and US patents,

following references were found to be cited by the Examiner -


IN249412 US7842703 EP1931681WO2005/075463 US20070249614 WO2005/075463

WO00/3681A2 - WO000/3681

FR-A-2661676 - FR2661676

Database Chemcats Chemical Abstracts service, Colombus, Ohio,

US; (2005-07-03),XP002414754

- Database Chemcats Chemical Abstracts Service, Columbus, Ohio,

US; (2005-07-03), XP002414754

WO 03/080578 A (MERCK SHARP AND DOHME [GB]; BROWN REBECCA ELIZABETH[GB]; DOUGHTY VICTOR) (2003-10-02) cited in the application

Wolff et al., Burger's Medicinal Chemistry and Drug Discovery (1994), Wiley-Interscience, Fifth Edition, vol. I: Principles and Practice, pp. 975-977

WO030/80578

- D2: Vippagunta et al., Advanced Drug Delivery Reviews (2001), 48, pp. 3

and 18

Database Chemcats Chemical Abstracts Service, Columbus, Ohio,

US; (2006-01-24), XP002414755

Conclusion2. From the analysis of allowed independent claims, it can be concluded

that the scope of the first independent claim of EP patent (EP1931681) is significantly broad when compared to its Indian (IN249412) and US (US7842703) counterparts. Following major differences could be observed-

While different Substituted Benzofused Derivatives falling under the ambit of following Markush structure (Formula I) were allowed in EP (EP1931681) and IN (IN249412) patents, only a specific Substituted Benzofused Derivative- 1-(3,4-dihydro-spiro-[2H-1-benzopyran-2,1’-cyclobutane]-4-yl)-3-(isoquinolin-5-yl)urea and its pharmaceutically acceptable salts were allowed in their US counterpart (US7842703).

Further, it could be concluded that references cited by the examiner during prosecution of Indian Patent application matches closely to those cited during prosecution of EP application in comparison to US patent application.



Section 8Information and Undertaking Regarding Foreign Applications –

8(1) Where an applicant for a patent under this Act is prosecuting either alone or jointly with any other person an application for a patent in any country outside India in respect of the same or substantially the same invention, or where to his knowledge such an application is being prosecuted by some person through whom he claims or by some person deriving title from him, he shall file along with his application or subsequently within the prescribed period as the Controller may allow— (a) a statement setting out detailed particulars of such application; and

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(b) an undertaking that, up to the date of grant of patent in India, he would keep the Controller informed in writing, from time to time, of detailed particulars as required under clause (a) in respect of every other application relating to the same or substantially the same invention, if any, filed in any country outside India subsequently to the filing of the statement referred to in the aforesaid clause, within the prescribed time.

8(2) At any time after an application for patent is filed in India and till the grant of a patent or refusal to grant of a patent made thereon, the Controller may also require the applicant to furnish details, as may be prescribed, relating to the processing of the application in a country outside India, and in that event the applicant shall furnish to the Controller information available to him within such period as may be prescribed.


Case Study - 4• IN212695 Assigned to Allergan Inc.

Application Date 20-10-2003; Grant Date 14-12-2007)

• Claim 1: A composition comprising a blend of a timolol component present in an amount effective to reduce ocular hypertension when applied to a hypertensive eye, and a hypotensive lipid component, different from the timolol component, present in an amount effective to reduce ocular hypertension when applied to a hypertensive eye,. said composition when applied to an eye being effective to treat ocular hypertension, the hypotensive lipid component being selected from the group consisting of cyclopentane E-ethyl heptenamide-5-cis-2- (3α-hydroxy-S-phenyl-l-trans-pentenyl)- 3,5-dihydroxy,[1α.2β,3α,5α], pharmaceutically acceptable salts thereof and mixtures thereof.



Ajanta Pharma Vs. Allergan IncAjanta filed revocation petitions on the bases of obviousness and Breach of section (8) of IPA:– The counsel submitted that Form 3 Dt. 20.01.2004 furnished by the

respondent in IPO indicated that Korea, New Zealand, Canada, China and Japan were pending applications. However, the application numbers of the same were not disclosed.

– No information on the prosecution of EPO and US counterpart applications was furnished. According to the counsel, corresponding US application No. 10/153,043 which was being prosecuted by the respondent and response to the office actions in US were filed before the response to FER in India.

– EPO issued its own Examination report February 11, 2005 in respect of the corresponding application (Page 388 - 385; Exhibit EA3 to the MP).

The IPAB found that invention is obvious and section 8 violation has been proved. Based on the observations revocation application was allowed and the grant of Patent No.212695 was set aside.

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