FORM 2
THE PATENTS ACT, 1970
THE COMPLETE SPECIFICATION
(See section 10)
1. THE METHOD OF TREATING TUBERCULOSIS.
2. Dr. Bakulesh Mafatlal Khamar residing at 201, "Ashadha" Vasundhra Colony, Gulbai Tekra, EUisbridge, Ahmedabad- 380006, Gujarat, India, Nationality Indian.
3. The following specification describes the nature of this invention.

THE METHOD OF TREATING TUBERCULOSIS
The invention relates to the method of treating tuberculosis comprises use of a microorganism Mycobacterium w for the treatment of tuberculosis.
Tuberculosis is a major communicable disease worldwide. It is a major cause of morbidity and mortality worldwide (developing countries' as well as developed countries). This is inspite of modern chemotherapy. The modern chemotherapy is widely available and effective. It is an infection caused by mycobacterium tuberculosis. There has been resurgence of tuberculosis recently. Resurgence of tuberculosis is putting lot of pressure on health care system and society. It is believed that almost 2 billion persons are infected with mycobacterium tuberculosis and 3 million persons die each year from the disease.
Mycobacterium Tuberculosis is slowly growing organism. It is responsible for tuberculosis. It is a chronic disease and needs long term treatment. Inspite of modern day chemotherapy tuberculosis treatment lasts for at least 6 months. The treatment comprises of two components i.e. intensive phase and continuation phase. The purpose of intensive phase is to kill microorganisms which are dividing (growing) and render the tissues (sputum) negative of organism. If treatment is stopped at this point them there is a high relapse rate (more than 20%). This is due to organisms which lie dormant and persists in the tissues (persistors). The continuation phase is to kill persistors and bring relapse rate as low as possible (less than 5%). Due to longer duration of treatment (more than six months) compliance is a problem. To improve compliance the therapy is given as a directly observed therapy (DOT). This increases the cost of therapy significantly..
Results of modern chemotherapy in treatment failure cases are not encouraging. It takes a longer time for effective treatment. This is particularly so when organisms are resistant to Rifampicin and Isoniazid. The infectiqn with organisms resistant to rifampicin and INH are also known as multidrug resistant tuberculosis. This is a most challenging infection to manage. For this

group of patients there is a need to provide an additional novel therapy. The therapy should be effective to reduce the burden of treatment failure cases. The therapy should also be effective in management of treatment failure cases including MDR tuberculosis.
It is also established that in a community best way to reduqe ifltidence of MDR is to treat fresh cases which are sensitive to primary dru§ therapy effectively in that community.
For this reason the efforts are being made to find out new therapeutic agents/regimen to decrease duration therapy and still keep relapse rate lower. Faster sputum conversion reduces the intensive phase and there by helpful in decreasing duration of therapy. It also decreases spread of disease in the society and also help in improving compliance from patient resulting in improved success rate and decreased prevalence of disease in community.
None of the attempts made so far has been successful.
UK patent 2236480 describes tuberculosis vaccine. The UK patent describes vaccine to provide protection against tuberculosis. It describes its efficacy in animals (mice and guinea pigs) in preventing tuberculosis. It also describes its safety when used in animals.
Surprisingly it is found that therapeutic agents comprising of Mycobacterium w or its components/fractions as an active agent are capable of achieving this goal. Use of such compositions are found to improve sputum conversion at least by 4 weeks. They also improve cure rate and relapse rate.
They are useful in all categories of disease. They seems to be more potent therapeutic agent as effects seen, are not achieved with any other agents known till date.

SUMMARY OF THE INVENTION
According to present invention, pharmaceutical compositions made from 'Mycobacterium w' (Mw) are found to be useful in management of tuberculosis. It is observed that administration of mycobacterium w containing pharmaceutical composition is effective in faster sputum corivers^n. It also improves time for relief from symptoms. It also improves cure rates as well as relapse rates.
Mycobacterium w used in the present invention is a non-pathogenic, cultivable, atypical mycobacterium, with biochemical properties and fast growth characteristics resembling those belonging to Runyons group IV class of Mycobacteria in its metabolic and growth properties but is not identical to those strains currently listed in this group. It is therefore thought that (Mw) is an entirely new strain.
The species identity of Mw has been defined by polymerase chain reaction DNA sequence determination and differentiated from thirty other species of mycobacteria. It however differs from those presently listed in this group in on respect or the other. By base sequence analysis of a polymorphic region of pattern analysis, it has been established that Mw is a unique species distinct from many other known mycobacterial species examined which are: M. avium, M. intracellulare, M. scrofulaceum, M. kansasii, M. gastri, M. gordonae, M. shimoidei, M. malmoense, M. haemophilum, M. terrae, M. nonchromogenicum, M. triviale, M. marinum, M. flavescens, M. simian, M. szulgai, M. xenopi, M. asciaticum, M. aurum, M. smegmatis, M. vaccae, M. fortuitum subsp fortuitum, M. fortuitum subsp. Peregrinum, M. chelonae subsp. Chelonae, M. chelonae subsp. Abscessus, M. genavense, M. tuberculosis, M. tuberculosis H37RV, M. paratuberculosis.
The object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for the treatment of tuberculosis.

Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for decreasing relapse rate of tuberculosis.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for quicker symptomatic relief in tuberculosis.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for faster regaining of normal health in tuberculosis.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for improvement of sputum conversion rate in tuberculosis.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for faster sputum conversion in patients suffering from tuberculosis.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for use along with chemotherapeutic agents.
Yet another object of the present invention is to provide the method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents

obtained from Mw for treatment of all categries of tuberculosis including treatment failure as well as MDR tuberculosis.
Yet another object of the present invention is to provide the*method of treating tuberculosis comprising administration of a pharmaceutical composition containing 'Mycobacterium w' (Mw) with or without constituents obtained from Mw for reduction in duration of treatment of tuberculosis.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the invention the composition, the method of preparation, HPLC characteristic its safety and tolerability, methods of use and outcome of treatments are described in following examples. The following are illustrative examples of the present invention and scope of the present invention should not be limited by them.
EXAMPLE 1. THE PHARMACEUTICAL COMPOSITIONS:
A. Each dose of 0.1 ml of therapeutic agent contains:
Mycobacterium w., (heat killed) 0.50 x 109
Sodium Chloride I. P. ... . 0.90% w/v
Tween80 0.1% w/v
Thiomerosal I. P. ... 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
B. Each dose of 0.1 ml of therapeutic agent contains:
Mycobacterium w., (heat killed) 0.50 x 109
Sodium Chloride I. P. ... . 0.90% w/v
Triton x 100 0.1% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)

Water for injection I. P.

q. s. to 0.1 ml

C. Each dose of 0.1 ml of therapeutic agent contains:
Mycobacterium w., (heat killed) 0.50 x109
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
D. Each dose of 0.1 ml of therapeutic agent contains
Extract of Mycobacterium w after sonication from 1x1010 Mycobacterium w
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
E. Each dose of 0.1 ml of therapeutic agent contains
Methanol Extract of 1x1010 Mycobacterium w
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
F. Each dose of 0.1 ml of therapeutic agent contains
Chloroform Extract of 1x1010 Mycobacterium w
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
G. Each dose of 0.1 ml of therapeutic agent contains
Acetone Extract of 1x1010 Mycobacterium w

Sodium Chloride I. P. 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v

(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
H. Each dose of 0.1 ml of therapeutic agent contains
Ethanol Extract of 1x1010 Mycobacterium w
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
I. Each dose of 0.1 ml of therapeutic agent contains
Liticase Extract of 1x1010Mycobacterium w
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal f. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
J. Each dose of 0.1 ml of therapeutic agent contains
Mycobacterium w (heat killed) 0.5x107
Extract of mycobacterium w obtained 1x103 Mycobacterium w by disruption,
solvent extraction or enzymatic extraction.
Sodium Chloride I. P. ... . 0.90% w/v
Thiomerosal I. P. ... . 0.01% w/v
(As a Preservative)
Water for injection I. P. q. s. to 0.1 ml
Example 2. The Process of preparing a pharmaceutical composition
A. Culturing of Mycobacterium w.
i) Preparation of culture medium.
Mycobacterium w is cultured on solid medium like L J medium or
liquid medium like middle brook medium or sauton's liquid medium.

For better yield middle brook medium is enriched. It can be
preferably enriched by addition of glucose, bactotryptone, and
BSA. They are used in ratio of 20:30:2 preferably.
The enrichment medium is added to middle brook medium. It is
done preferably in ratio of 15:1 to 25:1 more preperably in ratio of
20:1.
ii) Bioreactor operation
a) Preparation of vessel:
The inner contact parts of the vessel (Joints, mechanical seals, o-ring/gasket grooves, etc.) should be properly cleaned to avoid any contamination. Fill up the vessel with 0.1 N NaOH and leave as such for 24 H to remove pyrogenic materials and other contaminants. The vessel is then cleaned first with acidified water, then wit ordinary water. Finally, the vessel is rinsed with distilled water (3 times) before preparing medium.
b) Sterilization of bioreactor
The bioreactor containing 9L distilled water is sterilized with live steam(indirect). Similarly the bioreactor is sterilized once more with Middlebrook medium. The other addition bottles, inlet/outlet air filters etc. are autoclaved (twice) at 121°C for 15 minutes. Before use, these are dried at 50° C oven.
c) Environmental parameter
i. Temprature: 37+ 0.5° C
ii. pH : 6.7 to 6.8 initially.

B. Harvesting and concentrating
It is typically done at the end of 6th day after culturing under aseptic condition. The concentration of cells (palletisation) is done by centrifugation.
C. Washing of cells
The pallet so obtained is washed minimum three times with normal saline. It can be washed with any other fluid which is preferably isotonic.
D. Adding pharmaceutically acceptable carrier.
Pyrogen free normal saline is added to pallet. Any other pyrogen free isotonic fluid can be used as a pharmaceutical carrier. The carrier is added in amount so as get to desired concentration of active in final form.
E. Adding preservative
To keep the product free from other contaminating bacteria for its self life preservative is added. Preferred preservative is thiomesol which is used in final concentration of 0.01 % w/v.
F. Terminal Sterilization
Terminal sterilization can done by various physical methods like application of heat or ionizing radiation or sterile filtration.
Heat can be in the form of dry heat or moist heat. It can also be in the form of boiling or pasturisation.
Ionizing radiation can be ultraviolet or gamma rays or mircrowave or any other form of ionizing radiation.

It is preferable to autoclave the final product.
This can be done before after filling in a final packaging.
G. Quality Control
i.The material is evaluated for purity, sterility.
ii.The organisms are checked for acid fastness after gram staining.
iii.lnactivation test : This is done by culturing the product op L J medium to find out any living organism.
iv.Pathogenicity and/or contamination with pathogen.
The cultured organisms are infected to Balb/c mice. None of the mice should die and all should remain healthy and gain weight. There should not be any macroscopic or microscopic lesions seen in liver, lung spleen or any other organs when animals are killed upto 8 weeks following treatment.
v.Biochemical Test: The organism is subjected to following biochemical tests:
a) Urease
b) Tween 80 hydrolysis
c) Niacin test
d) Nitrate reduction test
The organism gives negative results in urease, tween 80 hydrolysis and niacin test. It is positive by nitrate reduction test.

H. Preparation of constituents of Mycobacterium w. The constituents of Mycobacterium w can be prepared for the purpose of invention by:
I. Cell disruption
II. Solvent extration
III. Enzymatic extraction.
The cell disruption can be done by way of sonication or use of high pressure fractionometer or by application of osmotic pressure ingredient.
The solvent extraction can be done by any organic solvent like chloroform, ethanol, methanol, acetone, phenol, isopropyl alcohol, acetic acid, urea, hexane etc.
The enzymatic extraction can be done by enzymes which can digest cell wall/membranes. They are typically proteolytic in nature. Enzyme liticase and pronase are the preferred enzymes. For the purpose of invention cell constituents of Mycobacterium w can be used alone in place of mycobacterium w organisms or it can be added to the product containing mycobacterium w.
Addition of cell constituents results in improved efficacy of the product.

EXAMPLE 3. CHARACTERISTICS OF CONSTITUENTS OF
MYCOBACTERIUM W BY HPLC ANALYSIS.
The constituents of mycobacterium w. used for the purpose of invention when subjected to HPLC analysis gives a single peak at 11 minutes. No other
it
significant peaks are found beyond. The peak is homogenous and devoid of any notch suggesting homogeneity of material obtained
HPLC analysis was done using a waters system high performance liquid chromatography apparatus

Column: Novapak c1860A, 4|im, 3.9 x 150mm.
The guard column: Novapak c 18
Column Temperature: 30° c
Flow rate: 2.5 ml/min
Injection volume: 25nL
Mobile phase:
Solvent A: HPLC grade methanol.
Solvent B: HPLC grade methylene chloride
Binary gradient:
The HPLC gradient in itially comprised 98%(v/v) methanol (solvent B)
The gradient was increased linearly to 80%.
A and 20% B at one minute; 35% A and 65% B at 10 minutes, held for 5 seconds and then decreased over 10 seconds back to 98% A and 2% B.
EXAMPLE 4. Following examples provides methods of use as well as efficacy of Mycobacterium w derived pharmaceutical composition in treatment of tuberculosis.

To find out improvement in sputum conversion rate of patients with
sputum positive primary pulmonary tuberculosis a group of patients
was treated with standard chemotherapy mpicin, INH, Pyrizinamide, ethambutol), the other group wa\ given standard chemotherapy with intradermal Mycobacterium w. Mybasterjum w was given at baseline, on day 15, day 30 and day 45. In all patients sputum was evaluated on day 15, day 30 and day45 and day 60. The sputum conversion was found to be enhanced by at least 30 days. Sputum conversiuon rate at day 30 in group receiving Mycobacterium w was comparable or better to the sputum conversion rate at day 60 in a group not receiving Mycobacterium w.
Thus Mycobacterium w containing pharmaceutical compositions are useful in better and faster sputum conversion
In an another group of patients with a primary pulmonary tuberculosis patients were evaluated not only for sputum conversion but also for symptomatic relief and weight gain symptomatic relief is a subjective parameter for disease control while weight gain is an indirect objective parameter of disease control. The patients were divided into two groups. One receiving standard chemotherapy (Rifampicin + INH + Pyrizinamide + ethambutol) while the other group received standard chemotherapy with Mycobacterium w at interval of one month.
The group of patients receiving Mycobacterium w had weight gain of more than 2 kg while none of the patients in a group not receiving Mycobacterium w had weight gain more than 0.5 kg by 6 weeks.
Again sputum conversion at 30 days in group receiving Mycobacterium w was comparable to sputum conversion rate at 60 days in group not receiving Mycobacterium w.

Patients in group receiving Mycobacteium w started reporting symptomatic relief by day 15 which was seen in subjects not receiving Mycobacterium w by day 45.
Thus Mycobacterium w containing pharmaceutical compositions are useful in quick sputum conversion, quicker symptomatic relief and feeling of well being.
3 Multi drug resistant (MDR) tuberculosis is a difficult to manage problem. The treatment lasts much longer as it is difficult to achieve faster sputum conversion in this group of patients. The Mycobacterium w was evaluated in a group of patients having MDR as demonstrated by sputum culture evaluation. They were treated by ciprofloxacin, kanamycin, ethionamide, ethambutol, Pyrizinamide. In a randomised way half of patients received 0.1 ml of Mycobacterium w derived pharmaceutical composition intradermally at interval of one week. The group of patients receiving Mycobacterium w were found to be sputum negative by the end of two months while all the patients in a group not receiving Mycobacterium w were sputum positive at the end of two months. By three months only 15% of subjects were found to be sputum negative in a group not receiving Mycobacterium w.
Thus Mycobacterium w derived pharmaceutical compositions are effective in management of multi drug resistant tuberculosis.
4. Successfully treated patient with standard short course chemotherapy (DOT) with or without use of Mycobacterium w were followed up for more than 1 year for determination of relapse rate. Surprisingly it was found that use of Mycobacterium w is useful in reduction of relapse

rate. In a group receiving Mycobacterium w, none of the patients had a relapse compared to relapse rate of 4% in a group not receiving Mycobacterium w.
Thus Mycobacterium w derived pharmaceutical composition is helpful in reducing the relapse rate considerably. This is of great significance. Since it relapses are responsible for recurrent disease, emergance of MDR TB and persistence of infection in a society.
5. A group of patients with freshly diagnosed pulmonary tuberculosis and
bacterial load of 1+ as demonstrated by microscopy of sputum were
randomly assigned to receive modern chemotherapy or modern
chemotherapy with pharmaceutical composition derived from
Mycobacterium w given intradermally.
Bacterial clearance was evident on day 15 in group receiving Mycobacterium w. This was evident on day 45 in a control group.
This indicates that Mycobacterium w provides antitubercular action which is faster than modern chemotherapy.
6. In patients with pulmonary tuberculosis belonging to category II effect
of Mycobacterium w composition was evaluated. All patients received
standard chemotherapy comprising refampicin, INH, Pyrizinamide and
Ethambutol. In a randomized way one group received intradermal
injection of Mycobacterium w at interval of 15 days. All patients in the
group receiving Mycobacterium w became sputum negative by 8
weeks compared to less than 70% in a group not receiving
Mycobacterium w.
The findings suggests that Mycobacterium w containing composition possess potent antitubercular activity and provides better results earlier.

6. 24 sputum smear positive cases of pulmonary tuberculosis with treatment failure were included in study. They were all put on category -II anti-tubercular treatment; their weight and clraical symptoms were recorded, out of these 24 patients every alternate patient at random was also given injection of Mycobacterium w intradermally over the deltoid region initially and repeated every fortnight.
All the cases were followed up every fortnight. On day 15 the patient in the Mycobacterium w group showed an average weight gain of 2 kg. and 4 of 12 patients becamesputum negative. While in the control group there was average weight loss of 1 kg. and none of them 12 had sputum conversion.
Thus Mycobacterium w containing pharmaceutical compositions are useful in quick sputum conversion, quicker feeling of well being and improved health (weight gain ).

We claim
1. A method of treating tuberculosis comprises administration of a formulation which is prepared using Mycobacterium w or a pharmaceutical composition obtained from Mycobacterium w alone or in combination and also with or without adjuvants to a subject suffering from tuberculosis.
2. The method as claimed in claim 1 for treating tuberculosis is effective in conversion of sputum positive individuals to sputum negative individuals.
3. The method as claimed in claim 1 for treating tuberculosis is effective in faster sputum conversion.
4. The method of treating tuberculosis as claimed in claim 1 is effective in primary tuberculosis.
5. The method of treating tuberculosis as claimed in claim 1 is effective in treatment of treatment failure cases of tuberculosis.
6. The method of treating tuberculosis as claimed in claim 1 is effective in treatment of multi-drug resistant (MDR) tuberculosis.
7. The method of treating tuberculosis as claimed in claim 1 is effective in improving relapse rate of tuberculosis.
8. The method of treating tuberculosis as claimed in claim 1 is effective in faster weight gain.
9. The method of treating tuberculosis as claimed in claim 1 is effective when used with other modalities of treatment like chemotherapy.
10. The product as claimed in claim 1 contain mycobacterium w is killed mycobacterium w.
11. The Mycobacterium w as claimed in claim 1 and 10 is killed by physical method like,heat radiation most preferably by heat in form of autoclaving.
12. The product as claimed in claim 1 is obtained from mycobacterium w by sonication.

13. The product as claimed in claim 1 is obtained from mytfobacterium w by extraction.
14. The product as claimed in claim 1 and 13 is obtained from mycobacterium w is extracted by organic solvents.
15. The product as claimed in claim 1, 13 and 14 is extracted using solvent selected from chloroform, ethanol, methanol, acetone, phenol, isopropyl alcohol, acetic acid, urea, Hexane and like.
16. The formulation as claimed in claim 1 contains surfactant.
17. The surfactant as claimed in claim 16 can be a Tween 80.
18. The amount of surfactant as claimed in claim 16 and 17 is upto 0.4% preferably 0.1%.
19.The Mycobacterium w as claimed in claim 1 to 18 is a non-pathogenic, fast growing cultivable, atypical mycobacterium, with biochemical properties and growth characteristics resembling those belonging to Runyons group IV class of Mycobacteria in its metabolic and growth properties but is not identical to those strains currently listed in this group.
20. Mycobacterium w as claimed in claim 1 is urease negative, does not hydrolyse tween 80, does not produce niacin, provides strong positive response to nitrate reduction test.
21. The administration of formulation as claimed in claim 1 is by parental route.
22. The administration as claimed in claim 1 and 23 is by intramuscular subcutaneous, intradermal route and like but preferably by intradermal route.
23. The amount of mycobacterium w administered at a time to a subject as claimed in claim 1 is equal to or more than 1x 105 mycobacterium w.
24. The amount of mycobacterium w administered at a time to a subject as claimed in claim 1 is equal to or more than 107 mycobacterium w.
25. The amount of mycobacterium w administered at a time to a subject as claimed in claim 1 is most preferably 1x 108 to 1x 1010 mycobacterium w.

26. The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprises of incorporate cells of mycobacterium w alongwith pharmaceutical^ acceptable carrier and optionally a preservative in a single formulation wherein cells of mycobacterium w are not alive.
27.The pharmaceutical^ acceptable carrier as claimed in clain 1 is added in a way so as to have more than or equal to 1x 105 mycobacterium w in a unitary dosage, more preferably equal to or more than 1x107 mycobacterium w in unitary dosage most preferably between 1x108 to 1x109 cells of mycobacterium w in a unitary dosage form.
28. The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprising the steps of incorporating disrupted cells of mycobacterium w along with pharmaceutically acceptable carrier and optionally a preservative.
29. The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprising the steps of incorporating solvent extraction of mycobacterium w along with pharmaceutically acceptable carrier and optionally a preservative.
30.The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprising of incorporating enzymatic extraction of mycobacterium w along with pharmaceutically acceptable carrier and optionally a preservative
31. The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprising admixing product of claim 1 with product of claim 28 and/or claim 29 and/ or claim 30.
32. The process of manufacturing a pharmaceutical composition useful for treatment of tuberculosis comprise of adding adjuvant to product of claim 1, claim 4, claim 6, claim 8 or claim 10.
33. The adjuvant as claimed in claim 32 is selected from mineral oil, mineral oil and surfactant, Ribi adjuvant, Titer-max, syntax adjuvant formulation, aluminium salt adjuvant, nitrocellulose adsorbed antigen, immune stimulating complexes, Gebru adjuvant, super carrier, elvax

40w, L -tyrosine, monatanide (manide -oleate compound), Adju prime, Squalene, Sodium phthalyl lipopoly saccharide, calcium phosphate, saponin, melanoma antigen, muramyl dipeptide(MDP) and like.
Dated this 3rd day of, March 2003

DR. BAKULESH KHAMAR
DIRECTOR - RESEARCH
FOR CADILA PHARMACEUTICALS LTD.