BEFORE CONTROLLER OF PATENTS THE PATENT OFFICE, KOLKATA IN THE MATTER OF THE PATENTS ACT 1970 ( as amended) Section 15 read with Section 25 (1) In the matter of patent application No. 2662/KOLNP/2007 dated 21st February 2006 ( National phase entry date is 17th July 2007 ) by ABRAXIS BIOSCIENCE, LLC

Hearing on : 25.02.2014 Present: For Applicant : Ms. ARCHANA SHANKER ORDER M/s ABRAXIS BIOSCIENCE, LLC, an American company filed the above mentioned application titled “COMBINATIONS AND MODES OF ADMINSITRATION OF THERAPEUTIC AGENTS AND COMBINATION THERAPY” on 17th July 2007 through Ms. S.Banerje, Kolkata, claiming the priority to PCT Application No- PCT/US2006/006167 dated 21st February 2006 which in turn claimed the priority of USA patent Application No 60/654245 dated 18th February 2005. 2. On the receipt of the request for examination on 17th February 2009 the said application was examined. The application as originally filed contained 49 Claims. The First Examination Report was issued on 30th January 2012.However the FER was issued to a wrong address for service and accordingly fresh FER was issued again on 1st May 2012.

3. Subsequently the applicant filed its detailed response against the objection raised in the FER on 30th April 2013.

4. The instant application came up for hearing with respect to following objections being raised after consideration of the reply submitted by the applicant against the FER. A hearing was accordingly offered to the applicant containing the following objections vide a letter dated 15th October 2015 and held on 30th October 2015. Objections were as follows: A. Objections 1, 3-4, 6, 7, 1 3, of FER are maintained wrt amended claims as Applicant agent’s response to the above mentioned objections were not found persuasive. B. The claims as filed in the international phase were method of treatment claims which were amended as composition claims and filed at national phase. By the amendment the whole scope has changed and is not allowable. Thereby the voluntary amendment with form 13 filed has not been allowed.

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C. Without prejudice to the earlier objection the instant claims are examined. Amended claims 1-50 make reference to composition but are disguised method of treatment claims and still attract section 3(i). Amended claims 51-65 make reference to kit, but are disguised method of treatment claims with instructions to use the composition and still attract section 3(i). Further Amended claims 1-65 attracts section 3(e), 3(j) and 3(d) of act. Amended claims 51-65 attract section 3(n) of Act.. D. Claims 1-12, 13 refer to a composition which is actually a combination therapy contradicts the statement of a composition. Similarly the application shows no limit in the size of the particles. The paragraph [0162] states that it is a preferred embodiment of the present invention that the nanoparticles have "an average or mean diameter of no greater than about 1000 nanometers". This means that claim 1 covers particles having a diameter above 1000 nanometres, i.e. into the micron range, rendering the term "nanoparticles" completely meaningless. E. Dependent claims 3-5 make reference to route & mode of administration. F. Claims lack disclosure wrt the antibody claimed in claims 6, 7 . G. Claim 1, 2, 6, 7,9, 10, 11, 16, 18, 19, 20,25-28, 31, 33, 34, 37, 39, 40-43, 46-48, 5155, 57-59, 62 make reference to chemotherapeutic agent and gives an exhaustive list and size of nano particle size which is very wide & unsupported by complete specification. H. Claims 21-24 make reference to composition but are drafted wrt achievable effect or disease or targeted end. I. The application does not comply with the requirements of section 10(4) of the Act as there is no clarity or disclosure or support. The amendments filed introduce subject matter which extends beyond the content of the application as filed. There is no specific disclosure for a combination of taxane/albumin nanoparticles with the specific chemotherapeutic agents as claimed by present claims. Rather, the subject matter of each of these claims requires already one selection out of a list of specific agents. Consequently, the combination with any feature of present claims creates combinations of features which were not originally disclosed and broadens of subject-matter, thus infringes section 10(4) of the Act. J. The originally filed application discloses coating with albumin only in connection with paclitaxel whereas present claim 25-50, 64 broadly refers to any taxane. K. Further the instant application is unclear as skilled person is not taught in the patent how to work the invention over the whole scope of this term. Firstly, it is not apparent if it is just the taxane which are nanoparticles, or if both the taxane and albumin have to be nanoparticles. This is important because the description only enables the skilled person to use a material where both the taxane and the albumin are nanoparticles. L. Claim 1-2 refers to a composition comprising "nanoparticles comprising a taxane Page 2 of 13

and an albumin". However, the priority document does not provide a basis for a combination of the general substance class of "taxanes" in combination with albumin-containing nanoparticles. M. Claim 1 of the priority document relates to the general combination of a taxane with another chemotherapeutic agent. A specific embodiment wherein "taxane comprises albumin" is disclosed in claim 2. However, nanoparticles are not disclosed in claim 1 and 2. Paragraph [0025] of the priority document discloses "a combination therapy comprising a first therapy comprising taxane and a second therapy ... ". Albuminbound nanoparticles are disclosed in paragraph [0023] of the priority document, however this disclosre is restricted to the specific example of paclitaxel ("nanoparticle albumin bound paclitaxel (Abraxane™) ,). In contrast to this, in the opposed patent paragraph [0023] discloses: "nanoparticle compositions of a taxane (such as albumin-bound paclitaxel (Abraxane TM) ... " Therefore, "nanoparticles comprising a taxane and an albumin" is an intermediate generalisation from the disclosure of the priority document and as such is not entitled to priority. N. Reference is made to the following citations 1-3 were cited in FER, 4-8 are now cited 01 Wo01/89522 02 J.A. O"Shaughnessy et al., Breast Cancer Research and Treatment, val 88, no. suppl. 1, 2004, page S65, 27th Annual Charles A Coltman San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 8-11 December 2004 03 T.E. Stinchcombe et al., Breast Cancer Research and Treatment, val 94, no. suppl. 1, 2005, page S71, 28th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 8 September 2005 04 B. Damascelli et al., AJR, July 2003, val. 181 no. 1, 253-260 05 B. Damascelli et al., Cancer, 2001, 92, 2592-2602 06 A. Moreno-Aspitia and E.A. Perez, Clin. Breast Cancer, 2005 Oct, 6(4), 361-364 07 MIMS, January 2005, section 18 entitled "Neoplastic disorders" 08 R. Colomer, Oncology 2004, 18(14) suppl., 8-12 03 discloses the use of a combination of Abraxane with carboplatin for the treatment of cancer. Therefore claim 1 lacks novelty over 03. 04 discloses the effects of nab-paclitaxel on advanced squamous cell carcinoma cells of the tongue. Page 259, first paragraph refers to "ABI-007" . The final paragraph of the discussion (at page 260) states that: ABI-007 "deserves further investigation in combination with radiotherapy or other drugs or both". The discussion mentions 5-fluorouracil (an antimetabolite) and cisplatin (a platinumbased agent) as other drugs. Therefore the document suggest a combination of ABI007 with 5-fluorouracil or cisplatin and is therefore novelty destroying for claim 1. 05 relates to intraarterial chemotherapy using nab-paclitaxel. Page 2600 (Discussion) refers to "drug combinations" to overcoming drug resistance. Page 2601 first full paragraph in the left-hand column further discloses "A new polyoxyethylated castor Page 3 of 13

oil and alcohol free formulation of the taxane paclitaxel" which has been identified already in the title as "ABI007"". Page 2601, second full paragraph of discussion refers lethe mechanism of action of ABI-007 and cisplatin and states: "a synergistic action with cisplatin as well as with radiotherapy would be possible and potentially useful." Consequently the disclosure is a novelty-destroying because the skilled person carrying out the teaching has obtained a combination therapy as claimed in claim 1. Claim 1 therefore is not novel over 05. 06 is relevant prior as the patent is not entitled to the claimed priority. Page 1, final paragraph refers to "Albumin-bound paclitaxel (ABI-007; Abraxane®)". The final paragraph on the second page discloses that: ""Based on the synergistic potential observed in preclinical studies with the combination of gemcitabine and conventional pac/itaxel, which seems to translate into a high RR and better time to progression and survival in patients with MBC, the favourable toxicity profile observed with albumin-bound paclitaxel compared with Cremopho bound paclitaxel, and the better tolerability of weekly taxanes, the NCCTG is exploring the efficacy and tolerability of the combination of weekly gemcitabine and albumin-bound paclitaxel as first-line chemotherapy in patients with MBC. " This disclosure renders claim 1 non-novel. O.

The purpose of the present invention is to provide a combination of a taxane and another chemotherapeutic agent to treat cancer. 01 represents the closest prior art, since it discloses that Abraxane™ has several advantages over prior art taxol compositions which require cremophor as solubilizing agent. These advantages are (i) less toxicity; (ii) higher doses (up to 300 mg/m2); (iii) greater in vivo efficacy of ABI-007. The technical difference between 01 and the presently claimed subject matter relies in the combined use of Abraxane™ with an additional chemotherapeutic agent. The problem to be solved therefore reads as how to provide an improved anticancer treatment. The present application suggests to solve the posed problem by combining Abraxane™ with an additional chemotherapeutic agent selected from a list as defined in present claim 6. To combine medicaments which are directed to the same use is a straight-forward action for the skilled person. As long as there is no surprising effect resulting from such a combination the solution to the prosed problem as suggested by the present application is not considered inventive in the sense of section 2(1)(ja) of Act. The examining division does not agree with the applicant"s argument that the improved response rate for Abraxane™ in combination therapy over that of taxol in combination therapy as demonstrated by the present application was unexpected. As already pointed out above it was known from 01 that Abraxane™ is more efficient than taxol. The skilled person had therefore a reasonable expectation of success that Abraxane™ would also be more effective in combination therapy than taxol. 04 and 05 disclose a combination for treating cancer. Furthermore the documents disclose nab-paclitaxel and another chemotherapeutic agent. Therefore each of the documents could represent the closest prior art. And in view of the above citations inventive step is not acknowledged u/s 2(1)(ja) of Act.

5. The applicant submitted the following with respect to the hearingPage 4 of 13

A. That with respect to the objections of FER and to further clarify the invention, the claims were amended. The amended claims are directed to a composition for the treatment of proliferative diseased and finds support in the patent specification and the said revisions are carried out under Section 57(6) of the Act. The scope of the claims is clearly within the scope of the original PCT claims and patent specification. The patent specification on paragraphs 0088 and 0089 explicitly discloses the composition. The claimed combination of nanoparticles and at least one chemotherapeutic agents recited in claim 1 is clearly and unambiguously derivable from the disclosure of the application as filed. The method of use claimed in the original claims subsumed the scope of the composition which was in effect used in the process. The composition claims are therefore within the scope of the previous filed claims and therefore within the bounds of section 59 of the Indian Patent Act. The patent specification in the following paragraphs clearly provides a composition comprising nanoparticle and the chemotherapeutic agent. The said paragraph includes the following 0031, 0049, 0050, 0072, 0073, 0075, 0076, 0077, 0078, 0079, 0080,0081.[Para 0065] defines the chemotherapeutic agent. In particular, the claimed composition is disclosed in [paras 0088 and 0089] and [Paras 0161 to 0176] of the patent specification. The examples in the patent specification in particular example 19 provides the phase I study of Abraxane and carboplatin. Example 9 provides combination studies of the composition Abraxane with other agents. The applicant also cited the following case lawsa. Glaverbell versus Anand Mahajan, 2009(41)PTC207(DeI) states- "The jurisdiction necessary to allow the amendment of a claim in the specification vests with the High Court, once the validity of the patent has been challenged in a patent infringement suit. The claims can be amended and such amendment may be allowed provided that is it clarificatory or elaborative in nature and also, that it does not alter the scope of the claim or introduce any new claim in the invention which was not present

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the original invention. Thus, the scope of enquiry in relation to amendments in the patent claim is limited to the extent as to whether it introduces any new claim which extends the scope of the monopoly rights of the patentee. - Para 17

b. Solvay Fluor GmbH versus E.I. Dupont de Nemours and Company, IPAB, Order No. 1ll of 2010 states - The purpose of making an amendment to a patent is to avoid a finding of invalidity in a revocation proceeding. Of course, amendment may be made at any time during the lifetime of a patent. - para 23 Section 58 of the Act, gives the court the power, in revocation proceedings wherein the validity of a patent is put in issue, to allow the proprietor of the patent to amend the specification of the patent, "in such manner, and subject to such terms as the court... thinks fit". Plainly seen, this is a wide discretion. - para 25

B. That the documents D3 and D6 are not prior art for the present application as being publications after the priority date of the application. Document O'Shaughnessy, J. et aL, DECEMBER 08 -11, 2004. ISSN: 0167 6806 (D2) has been acknowledged in para [0020] of the patent specification and deals with the pre-clinical modules that have shown significant improvement in the safety and efficacy of Abraxane compared to taxol in an individual with metastastic breast cancer.

C. That referring to relation to Dl (WOO 1/89522) Example 11 of Dl discloses results of a phase I clinical study of intravenous ABI -007 in solid tumors. The goal of this study was to determine the maximum tolerated dose (MTD) for ABI-007 and toxicity connected herewith. in general, the goal of clinical phase I is to determine pharmacokinetic, pharmacodynamics, as well as safety of the drug under investigation prior to assessing efficacy in clinical phase II. Thus, it was not at all a purpose of the study to show any therapeutic effect of Abraxane, let alone the combination with a second agent. Dl does not disclose combination. Dl confuses 'prior therapy' with 'combination therapy'. Specifically, Dl errs in equating a monotherapy followed by another monotherapy as 'combination. This is in clear contrast to the common understanding of a skilled person. Furthermore, prior therapies have not been considered relevant for the final result of the study of Dl. For example, Dl discloses that besides prior chemotherapies with doxorubicin, taxol, and Herceptin, "(p)atients had received many other commonly used drugs". These prior therapies have not been considered or described in more detail. None of these conditions are fulfilled by the situation described in Example 11 Dl, as in the case of prior therapies, the administration of the prior agent is stopped : as soon as the new therapy starts. Therefore the subject matter of the present invention is novel over D1. That D4 discloses ABI-007 and states that "it deserves further investigation in combination with radiotherapy or other drugs or both" (see page 260, 1st paragraph, left; emphasis added). In other words, D4 contains "mere Page 6 of 13

speculation" with regard to possible future applications rather than any clear technical teaching. In fact, D4 does not disclose any kind of composition of two or more elements as claimed in the present application. Thus, since D4 does not disclose the claimed composition in the sense of a clear technical teaching, D4 does not anticipate the subject-matter of claim 1.That That D5 only discloses that "if the feasibility of intraarterial use were to be confirmed,a synergistic action with cisplatin as well as with radiotherapy would be possible and potentially useful" (see page 2601, right column, 1st and 2nd paragraphs,emphasis added). D5 therefore contains a mere speculation with regard to the possible future applications rather than any clear technical teaching. The disclosure on this based on two conditions or speculations: First, the feasibility of intra-arterial use still needs to be determined and only if this turns out to be feasible, the document goes on and speculates about future therapeutic options. In view of the above, D5 does not provide any clear and unambiguous technical teaching and cannot be considered an enabling disclosure.

D. That Documents D3 and D6 which were published after the priority date are not relevant when assessing inventive step. The subject matter of claim 1 is inventive over Dl. As already shown above with respect to novelty of the present invention, DI does not disclose the use of Abraxane in combination with a second chemotherapeutic agent, nor does it suggest using combination for treating cancer. Patients with prior chemotherapy referred to in Example 11 do not seem to be a purposeful selection but rather random. This view is supported by the fact that patients previously treated with doxorubicin, Taxol, and Herceptin were pooled in one group without differentiating the effect of a particular prior therapy in combination with ABI-007. This would be particularly important since these three drugs belong to different groups of anti-cancer medicaments. However, data on prior therapies are completely disregarded in Dl. Therefore, Dl in fact only discloses the use of Abraxane in a monotherapy for treating cancer. The distinguishing feature of the present invention is the use of a further chemotherapeutic agent according to claim 1. The technical effect of this feature is an improved cancer therapy .Dl does not give any incentive as to how the efficacy of the cancer therapy can be improved, much less it points to the use of a combination therapy in order to solve the technical problem of the invention. Based on Dl alone, the skilled person would not try to combine Abraxane with a second therapeutic agent in order to improve the efficacy of cancer therapy. Hence, Dl neither discloses nor suggests a combination cancer therapy with Abraxane and a second agent when taken alone. That Dl does not teach or suggest the use of a second chemotherapeutically active agent in addition to ABI-007 in the form of a combination therapy in order to improve the results of cancer treatment. Even assuming for the sake of argument that D8 would show an advantage of treating metastatic breast cancer with paclitaxel and gemcitabine as compared to paclitaxel alone, the skilled person would not be inclined to combine the teaching of the set wo documents since Abraxane has properties different to paclitaxel solved in Cremophor® (see discussion above). Moreover, even if the skilled person would try a combination therapy in view Page 7 of 13

of Dl and D8, there would be no reasonable expectation of success in the sense of T296/93inview of these documents.Therefore, the subject-matter of claim 1 is based on an inventive step in view of Dl in combination with D8. That D7 discloses conventional Taxol (paclitaxel), especially in combination with cisplatin and trastuzumab for treating non-small cell lung cancer and advanced or metastatic breast cancer, respectively. However, it is not indicated whether these combinations of drugs demonstrate any advantageous effect. Additionally, as discussed above, Abraxane has different properties than paclitaxel alone and cannot be considered as a paclitaxel equivalent. Therefore, even if D7 teach to combine paclitaxel as an active compound with further chemotherapeutic agents for distinct indication, the skilled person would not combine Abraxane with a second drug with reasonable expectation of success (see e.g. T 385/07). Therefore, the subject-matter of claim 1 is based on an inventive step in view of Dl and D7. That as shown above, Dl disclose only administering ABI-007 for treating cancer, D4 merely invites to investigate drugs which could be suitable to be administered in combination withABI-007. This document does not teach which drugs, if any, would demonstrate a improved effect with ABI-007. Therefore, the skilled person again would have to start an investigation program in a "try-and-see" attitude without any pointer to using combinations suitable to provide an improved anti-cancer therapy. For the reasons set forth above, such disclosure does not make the questionable invention obvious in view of the prior art. Hence, the subject-matter of claim 1 is inventive in view of Dl in combination with D4. That D5 suggests for ABI-007 that "a synergistic action with cisplatin as well as with radiotherapy would be possible and potentially useful". However, as it was correctly noted by 01, this suggestion was made with the purpose of overcoming drug resistance (see page 2600, right column, 1st paragraph). The technical problem to be solved by the present invention is to provide a combination therapy demonstrating an advantageous effect. Thus, D5 would not even be considered as a teaching which can be combined with the teaching of Dl in order to achieve the claimed invention. Therefore, the subject-matter of claim 1 is inventive over Dl in combination with D5. That D5 discloses the results of phase I study of patients with squamous cell carcinoma of the head and neck with ABI-007. Furthermore, D5 merely suggests that a combination with cisplatin would be possible and may potentially be useful (see page 2601, left column, 1st full paragraph).As set forth above, it could not be predicted by the skilled person that a combination therapy using Abraxane instead of conventional paclitaxel would behave in similar way and demonstrate the advantageous effect observed with paclitaxel. Therefore, the subject-matter of claim 1 is not obvious in view of D5 alone. The consultation of D4 in addition to the teaching of D5 does not remedy the deficiencies of its disclosure. Specifically, D4 simply invite to try different chemotherapeutic compounds known in the art in combination with ABI-007. However, as discussed above, theme re suggestion does not allow to predict an improved effect of the claimed combinations in cancer therapy. Thus, the subjectmatter of claim 1 is inventive in view of D5 alone or in combination with Page 8 of 13

D4. That D4 discloses a novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles for treating advanced squamous cell carcinoma of the tongue. Because the treatment with paclitaxel in albumin nanonarticles "does not interfere with and can potentially be integrateinto other therapeutic options, it deserves further investigation in combination withradiotherapyor other drugs ... " (see page 260, left column, 1st paragraph, emphasis added).5-fluorouraciland cisplatin are indicated as most widely used drugs in other context, not related to a possible combination, (see page 258, right column, 1st paragraph).Thus, the teaching of D4 is merely speculative and at best an intention to start an investigation program in order to find out an alternative combination therapy. In contrast tothestatementof01, D5 does not indicate an advantageous effect of ABI-007 with cisplatin, but rather speculate about such an effect based on the absence of interference with ABI-007.Howeversolely the absence of interference does not automatically means that the effect will be advantageous. Hence, the skilled person will not be seriously directed by D5 based on D4 in his attempt to achieve advantageous effect with ABI-007 with another anti-cancer drugs. Therefore, the subject-matter of claim 1 is inventive over D4 alone or in combination withD5.In view of the above submissions, we respectfully submit that objection nos. 1, 2, 3,4 and 5 be set aside. E. That as per section 10(4) of the Indian Patent Act the complete specification has to disclose the invention in a manner sufficiently clear and complete for it to be carried out by persons skilled in the art. An invention is in principle sufficiently disclosed if at least one way is clearly indicated enabling the person skilled in the art to carry out the invention. This requirement is fulfilled by the present patent since the description contains numerous examples of how the invention can be carried out. In fact, the present description provides clear teaching with respect to Abraxane in combination with several second chemotherapeutic agents (such as carboplatin, trastuzumab, gemcitabine,

rapamycin etc.) and different cancer types (such as metastatic breast cancer, colon carcinoma, lung carcinoma etc.). Reference is made in this regard to pages 18-26 of the patent specification.The skilled person would be able to carry out the invention over the entirescopeofclaim1usingcommon general knowledge with respect to wellknown therapeutically active compounds of the classes listed in claim 1 and applying dosage schemes disclosed in Examples and in Table 1 and known for these compounds in the art. It is also submitted that a skilled person will indeed be able to carry out the invention based on the description since nanoparticles comprising both paclitaxel and albumin are disclosed. The features "taxane" and "albumin" are connected by the word "and", so that the skilled person would unambiguously understand that nanoparticles are formed of two components :namely a taxane and an albumin. This is in line with the various passages in the description referring to"nanoparticles comprising paclitaxel and albumin" (such as, page 6, line 46 and lines 48-49), "paclitaxel albumin nanoparticles" (page 7, line 43), or "paclitaxel albumin nanoparticle composition" (page 7, line 44). As the patent contains sufficient and enabling description how to make these nanoparticles, the objection is unsubstantiated.

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F. That the paragraph [0162] states that it is a preferred embodiment of the present invention that the nanoparticles have "an average or mean diameter of no greater than about 1000 nanometers". Paragraph [0162] states that it is a preferred embodiment of the present invention that the nanoparticles have "an average or mean diameter of no greater than about1000nanometers"The statement is therefore incorrect and therefore should be withdrawn. G. That the examples in the patent specification are only illustrative and they need not be any specific examples. Under Section 10(4) of the Indian Patents Act, it is not necessary to provide examples in the patent specification and the specification has to sufficiently disclose the invention in order to enable a person skilled in the art to carry out the invention. The patent specification is replete with disclosure and examples to enable a person skilled in the art to arrive at the composition of the present invention. Reconsideration of this objection is requested.

H. That with respect to the allegation that the priority document does not provide a basis for a combination of the general substance claim of "taxane" in combination with albumin- containing nanoparticles, it is humbly submitted that the priority application discloses in paragraph [0025] the first therapy as comprising taxane and in the following paragraph [0026], "nano-particle albumin bound paclitaxel" and, alternatively, "nanoparticle albumin bound docetaxel" are indicated as the first therapy making further inventions"; and (2) that the description must be fair i.e. it must not be unnecessarily difficult to follow. " (Page 266). I. That the examples in the patent specification are only illustrative and they need not be any specific examples. Under Section 10(4) of the Indian Patents Act, it is not necessary to provide examples in the patent specification and the specification has to sufficiently disclose the invention in order to enable a person skilled in the art to carry out the invention. The patent specification is replete with disclosure and examples to enable a person skilled in the art to arrive at the composition of the present invention. Reconsideration of this objection is requested. The skilled person reading the description as a whole and recognizing that although a taxane in paragraph [0025] is not specified as being a nanoparticle albumin bound taxane, the particular embodiments of the invention disclosed in paragraph [0026] and in Examples all relate to nanoparticles. Even the background section makes it clear by discussing Abraxane in comparison to Cremophor containing solution (see paragraphs [0019][0023]). Therefore, the skilled person would understand that the invention in fact relates to a nanoparticle comprising albumin-bound taxane. Consequently, as the skilled person can derive the subject-matter of the claim directly and unambiguously, using common general knowledge, from the previous application as a whole, the priority claim is valid.

J. That Section 3(d) does not apply to compositions of the present case in view of the order passed by the Hon'ble IPAB in Ajanta Pharma Vs. Allergan. The combination mentioned in the explanation can be only mean a combination of two or more of the derivatives mentioned in the explanation or combination of one or more of the derivatives of the known substance which may result in a significant difference with regard to efficacy". Page 10 of 13

K. That Post-filing data acceptable to overcome grounds of non-obviousness with respect to the following : -Knoll Pharmaceuticals Company, Inc. Vs. Teva Pharmaceuticals USA, Inc. [367 F.3d 1381} in para 138 the Court held that – "Evidence developed after the patent grant is not excluded from consideration, for understanding of the full range of an invention is not always achieved at the time of filing the patent application. It is not improper to obtain additional support consistent with the patented invention, to respond to litigation attacks on validity. There is no requirement that an invention's properties and advantages were fully known before the patent application was filed, or that the patent application contains all of the work done in studying the invention, in order for that work to be introduced into evidence in response to litigation attack. Nor is it improper to conduct additional experiments and provide later-obtained data in support of patent validity."

5. Two pre grant oppositions were filed against the instant application after the hearing with respect to Section 14 was conducted. Notice was issued under Rule 55 for both the cases. The opponent of the pre-grant opposition did not file any reply in evidence for the both the pre-grant oppositions. Hearing was offered for both the cases. The pre-grant applicant requested for adjournment for the both the pre-grant oppositions. However by an email the opponent informed the Controller that they are no more interested to pursue the matter. Accordingly there is no further need for any adjournment, the pre-grant oppositions are taken on record and disposed of. Opinion and Decision: The hearing notice contain the objection- The claims as filed in the international phase were method of treatment claims which were amended as composition claims filed at national phase. By the amendment the whole scope has changed and is not allowable. Thereby the voluntary amendment with form 13 filed has not been allowed.

The amendment of the claims from “Method of treating proliferative diseases” to “Composition comprising nanoparticles….” and other types of claims are not allowable under Section 59(1) as they are beyond the scope of claims originally disclosed. In the original set of claims there was not a single claim which relates to “composition claims “ or “kit claims” . Amended claims also attract Section 3(e), 3(j) and 3(d) of the Act. The section 13(3) of the Patent Act clearly states – “Where a complete specification is amended under the provisions of this Act before the grant of patent, the amended specification shall be examined and investigated in like manner as the original specification”.

Section 59(1) of the Patents Act ( as amended ) inter alia says –

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“No amendment of an application for a patent or a complete specification or any document related thereto shall be made except by way of disclaimer, correction or explanation, and no amendment thereof shall be allowed, except for the purpose of incorporation of actual fact, and no amendment of a complete specification shall be allowed, the effect of which would be that the specification as amended would claim or describe matter not in substance disclosed or shown in the specification before the amendment, or that any claim of the specification as amended would not fall wholly within the scope of a claim of the specification before the amendment” Hence it is clear that no amendment of the claims shall be allowed which would claim subject matters which are beyond the scope of the claims which are submitted during filing of the application. Only claims of the complete specification shall be allowed which would fall wholly within the scope of the claim of the complete specification before amendment. Further with respect to applications which are entering national phase the Section 10(4A) of the Act says“In case of an international application designating India, the title, description , drawings, abstract, and claims filed with the application shall be taken as the complete specification for the purposes of this Act” The agent submitted that the specification disclose the said compositions in paragraphs 0088 and 0089 and hence the revised claims directed to a “composition” should be allowed , as the scope of the amended claims is clearly within the scope of the original PCT claims. However in the PCT international phase there were 49 claims and all the claims were directed to method of treatment. It is well settled principle in the field of Patent law that –“ WHAT IS NOT CLAIMED IS DISCLAIMED”. In the matter of Electric and Musical Industries, Ltd. et al v. Lissen, Ltd. et al. (1939), 56 R.P.C. 23 it was said by Lord Russel – “The function of the claims is to define clearly and with precision the monopoly claimed, so that others may know the exact boundaries of the area within which they will be trespassers. Their primary object is to limit and not to extend the monopoly. What is not claimed is disclaimed. The claims must undoubtedly be read as part of the entire document, and not as a separate document; but the forbidden field must be found in the language of the claims and not elsewhere. It is not permissible, in my opinion, by reference to some language used in the earlier part of the specification to change a claim which by its own language is a claim for one subject-matter into a claim for another and a different subject-matter, which is what you do when you alter the boundaries of the forbidden territory. A patentee who describes an invention in the body of a specification obtains no monopoly unless it is claimed in the claims”. It is also said -"The office of a claim is to define and limit with precision what it is which is claimed to have been invented and therefore patented" in the matter of Harrison v. Anderston Foundry Co., L.R. I App. Cas. 574. Hence it is ample clear that if something is not claimed initially is actually disclaimed. In this particular application the reference to “compositions” may have been referred in the specification but it was not mentioned in anywhere in the Claims. The matter is disclaimed after the application is being filed in PCT International phase and the Page 12 of 13

application has to enter the national along with the claims of PCT International phase as per Section 10(4A) of the Act. This cannot be claimed afresh by making an application for amendment. Accordingly the amended claims are not allowable under Section 57 & Section 59 of the Act. Now since the instant application is a PCT national phase application, wherein the PCT claims being related to method of treatment claims are not allowable under Section 3(i) of the Act, and the proposed amended claims are not allowable under section 57 & Section 59 of the Act, there is no need to analyse or discuss the further objections which were raised in the Hearing letter. 6. On the above foregoing discussion, considering all facts and submissions made by the agent on behalf of the applicant hence I hereby refuse the instant application.

(S.KUNDU) Assistant Controller of Patents & Designs. CC : 1. M/s. ABRAXIS BIOSCIENCE, LLC. C% - Ms. ARCHANA SHANKER ANAND & ANAND B-41 NIZAMUDDIN EAST NEW DELHI-110013. 2. The System Administrator -for necessary uploading in the website. 3. File Record.

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