Thursday, March 19, 2015

IPO - Like a Rock

In the early 1990's when I visited the Indian Patent Office (IPO) for the first time, it was as gloomy and depressing as any other dysfunctional sarkari office. Over the years, it certainly seems to have changed for the better.

Now, at a time when, "advanced industrialised countries are ratcheting up global standards for intellectual property protection with monotonous regularity, keeping in view the interests of the dominant corporate interests" (Biswajit Dhar, FE), our patent office has been standing its ground.

Section 3(d) of Patents Act ensures that rights cannot be obtained for minor innovations, and this is being implemented quite effectively -


  • 2006 - India’s patent office refused to give Novartis AG a patent for Glivec (Imatinib), an extremely effective drug for a rare cancer - CML
  • 2012 - India’s Intellectual Property Appellate Board revoked a Roche Holding AG patent for a hepatitis C drug (Pegasys) saying technology involved in the drug’s invention was “obvious” and could be replicated easily.
  • January 2015 - India’s patent office rejected a patent application from the U.S. biotech firm Gilead Sciences Inc. for a Hepatitis C treatment (Sovaldi) , saying it lacked novelty and didn’t show significant efficacy over previously known compounds.
  • March, 2015 - IPO withdrew patent protection for an emphysema drug (Spiriva) marketed by Germany’s Boehringer Ingelheim GmbH, in response to an objection filed by Cipla.


What (or who) is the driving force behind this transformation of the Indian Patent Office?  What mechanisms do they have in place to ensure that Big Pharma do not get away with Evergreening? And, most importantly, what can the patent office do to improve our own abysmal record in encouraging innovations, and building innovative, world-class products?

Perhaps organisations like the Lawyers Collective had a strong role to play here.

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LINKS

* Key Medicines -  Patent Status in India -- http://www.lawyerscollective.org/drugs-list

* http://in.reuters.com/article/2015/01/14/gilead-india-patent-idINKBN0KN20V20150114

* India Patent Office -- http://www.ipindia.nic.in/

* (19Mar15) - WSJ - India's fight against Big Pharma is a Just War -- http://blogs.wsj.com/indiarealtime/2015/03/19/inside-india-indias-fight-against-big-pharma-patents-is-a-just-war/

* Biswajit Dhar (2014): IPR policy must drive innovation -- http://www.macroscan.net/pdfs/ipr_policy.pdf

Thursday, March 12, 2015

Yella's Discoveries




One of the simple pleasures of life is to find an Indian-sounding name in a piece of work that touches excellence. Quite often, I find myself waiting for the credits to roll at the end of a great movie, or flipping through the 'acknowledgements' section of a book, or a computer app, just to take delight at the number of such names that turn up.

Yesterday, I started on a book that had such a name right on the front-cover: Siddhartha Mukherjee's "The Emperor of All Maladies". It won the Pulitzer Prize in 2011 but, until now, I had put it away, assuming that it was a work of fiction that was somehow connected to Jumpa Lahiri's "Interpreter of Maladies". Never have I been so wrong about titles!

The book actually combines three things that I would never tire of -- history, science and technology. It is a biography of a disease we all dread - Cancer.

Right at the beginning of the story, amid 20th century scientists of Europe and USA struggling to understand this strange disease, an Indian name pops up in the most unlikely place and time - Yellapragada Subbarow at Harvard Medical School, 1923. Yella was a product of Madras Medical College, but his degree was not recognized, so he started all over again at Harvard as a biochemist, supporting himself by working as a part-time janitor, cleaning halls and toilet-bowls.

Down the road, he went on to discover the role of phosphocreatine, adenosine triphosphate (ATP) as an energy source in the cell, and developed methotrexate for the treatment of cancer. He discovered polymyxin widely used even today in cattle-feed and aureomycin (the first broad-spectrum antibiotic), and the first of tetracycline antibiotics. SubbaRow and his team of organic and biological chemists isolated folic acid from liver and a microbial source and then synthesized it in 1945. As Director of Research at Lederle, he  found in Hetrazan  (diethylcarbamazine (DEC), the cure for filariasis. The method for estimating phosphorous is called the Fiske-SubbaRow Method.

According to Banerjee, "Any one of these achievements should have been enough to guarantee him a professorship at Harvard. But Subbarow was a foreigner, a reclusive, nocturnal, heavily accented vegetarian who lived in a one-room apartment downtown, befriended only by other nocturnal recluses".

How is it that we never heard about him in our own school science textbooks?

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LINKS
  • Mukherjee, Siddhartha (2011): EMPEROR OF ALL MALADIES - A BIOGRAPHY OF CANCER, Scribner, 2011 -- url -- http://www.amazon.in/The-Emperor-All-Maladies-Biography/dp/1439170916 
  • Indian Academy of Clinical Medicine -- http://medind.nic.in/jac/t01/i1/jact01i1p96.pdf
  • Wiki - http://en.wikipedia.org/wiki/The_Emperor_of_All_Maladies
  • Yellapragada Subbarow (12 January 1895 – 9 August 1948) -- http://en.wikipedia.org/wiki/Yellapragada_Subbarow
  • Miracle Man of Miracle Drugs -- http://www.ysubbarow.info/ 



Saturday, March 07, 2015

Merchants of Rosy Imagery



Joseph Goebbels would have been quite pleased with this illustration.

It shows a somewhat effeminate Shah Alam, one of the last Mughal emperors in an opulent court , handing over a scroll - the "Treaty of Allahabad" - to Robert Clive, representative of the East India Company (EIC), in 1765.

Under this treaty, Clive was appointed as the new governor of Bengal, Orissa and Bihar, with full rights to collect taxes as EIC pleased -- one of the earliest cases of a sovereign state subcontracting its own work to a multinational corporation (MNC).  It was also a legal fig-leaf to cover a plunder that had started a few years earlier, after the Battle of Plassey (1757).

According to William Darylmple, "The entire contents of the Bengal treasury were simply loaded into 100 boats and punted down the Ganges... Clive transferred to the EIC treasury no less than £2.5m seized from the defeated rulers of Bengal – in today’s currency, around £23m for Clive and £250m for the company."

Recent research goes to prove that there had been no grand court scene at the court of Shah Alam. The scroll had actually changed hands at Clive's tent pitched in a parade ground. "As for Shah Alam’s silken throne, it was in fact Clive’s armchair, which for the occasion had been hoisted on to his dining room table and covered with a chintz bedspread."

EIC had commissioned an illustrator to create a grand image for the benefit of the British parliamentarians, and the general public. It worked beautifully. Over the next hundred years EIC reinvested the 'revenue' from East India, and public loans and grants, to build an vast army to conquer, subjugate and plunder the subcontinent.

According to Darlymple, the EIC merchants were merely taking advantage of a power vacuum in India. Between the time the first EIC ship sailed into Surat in 1608 with William Hawkins, and Robert Clive's 'treaty' of 1765 came a disaster that crippled the Mughal empire. Persian adventurer, Nader Shah had trotted down with 150,000 horsemen, defeated the Mughals at the Battle of Karnal (1739), and carried away treasures worth over GBP 87.5 million.

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LINKS

* WD - East India Company -- http://www.theguardian.com/world/2015/mar/04/east-india-company-original-corporate-raiders
* Rajiv Malhotra - Debating foreign funded NGOs -- https://www.youtube.com/watch?v=_OWY_haNDNI#t=2127








Friday, March 06, 2015

Rape and the Criminal Justice System


Two cases stand in sharp contrast today.

Case-I: Dimapur, Nagaland
Last month, on 24 Feb., 2015,  an immigrant trader in Dimapur, Nagaland was accused of raping a woman. He was arrested an lodged in the jail. Yesterday evening, a mob of over 1500 people barged into the jail, overpowered the guards, and dragged away the accused man. He was then lynched and had his body strung up on the town square.
Nagaland has one of the lowest incidence of crimes against women in India.  

Case-II: New Delhi, Delhi
More than three years' ago, on 16 Dec., 2012, a paramedic-student was gang-raped in a moving bus. The attack was so brutal that she succumbed to her injuries in a couple of weeks. In response to the huge public outrage that followed, a "fast-track" court was set-up. All the accused men were tried, and sentenced to death. The case, however, continues to linger under an appeal process. The remorseless ramblings of one the rapists is now the centrepiece of a BBC documentary "India's Daughter". 

If the legal maxim, "Justice delayed is justice denied" hold true, does the Indian Criminal Justice System inspire any public confidence or credibility? If this is how speedy justice is being administered by a "fast-track court", can the Nagas be faulted for lynching a rapist?


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LINKS

- Log kya kahenge? (what will people say?) -- http://www.buzzfeed.com/regajha/log-kya-kahenge
- BBC - India's Daughter - https://www.youtube.com/watch?v=qUvlwmIfyx0 (This link may not last -- YouTube seems to have agreed to GoI's demand to block this, at least in India)
- (5Mar15) - Salil Tripathy -- why it should be seen in India -- http://www.livemint.com/Opinion/34Ls4cgDsZaDbEH8TdLBmN/Why-Indias-Daughter-should-be-seen-in-India.html
- http://www.thehindu.com/opinion/op-ed/comment-article-rape-rhetoric-and-reality/article6705077.ec
- WSJ - A Rape Map of India -- http://blogs.wsj.com/indiarealtime/2013/01/03/a-rape-map-of-india/
- Parliamentary Debate -- http://www.ndtv.com/video/player/news/in-parliament-debate-on-documentary-on-delhi-gang-rape-india-s-daughter/358686?fb



Monday, March 02, 2015

Our Little Game of Pretence

Sometimes we act as though China does not exist. It is a disconcerting little game of pretence.

Yesterday, a top bureaucrat at the Indian Ministry of Commerce tweeted:



On the face of it, this looks like a useful nugget - until you start wondering who is no. 1. That is when everything comes into perspective.

It took India hundred years to grow its cement industry to about 360 million tonnes. China, on the other hand, expanded its cement production from less than 50 millon tonnes (mT) in 1978, to over 2000 mT in 2014. It now produces more than half the entire global production. Yet we think our achievement over the last 100 years is something "spectacular".

Now consider the Indian pharmaceutical industry. We claim to be a global powerhouse in generic medicines. And then comes along a BCG-CII report saying that Indian companies are completely dependent on Chinese imports for Active Pharmaceutical Ingredients (APIs), the most critical ingredient in the drug manufacturing process.

Here is what an ET report says:

Imports of APIs and advanced intermediates have grown close to 20 per cent a year from $800 million in 2004 to $3.4 billion now. China accounts for 58 per cent of such imports by value and 80 per cent by volume, trade estimates point out.
The essential drugs include Paracetamol, Ranitidine, Metformin, Amoxicillin, Ciprofloxacin, Acetyl Salicylic Acid, Ofloxacin, Cefixime, Ibuprofen, Ampicillin, and Metronidazole. A recent industry report pointed out any strain in the Sino-Indian relationship could cause a severe shortage of essential drugs.

This leaves us with one big puzzle. Why on earth do the Chinese companies continue to let India pretend to be a pharma powerhouse? Why don't they just go ahead with their APIs and manufacture the drug formulations themselves?

One expert suggests that they are just warming up for the next big thing - Biosimilars. Wonder if this is true...

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REFERENCES

* China Cement production -- http://www.igsnrr.cas.cn/xwzx/jxlwtj/201405/P020140522355603140914.pdf

* IBEF on the Indian Pharma Sector - http://www.ibef.org/industry/pharmaceutical-india.aspx

* USFDA lens on China is bad news for India -- http://www.business-standard.com/article/economy-policy/us-fda-scolds-chinese-api-maker-on-basic-mfg-problems-115010800858_1.html

* * (2014, OCt29, ET): Soma Das -- India relies on China for 90 per cent of drug raw materials -- http://articles.economictimes.indiatimes.com/2014-10-29/news/55559092_1_essential-drugs-bulk-drugs-apis

* (2014, Nov14, ToI): Sushmi Dey -- http://timesofindia.indiatimes.com/india/Overdependence-on-China-for-drug-ingredients-worries-NSA/articleshow/45278715.cms

Saturday, February 28, 2015

2015 - February: Interesting Articles & Links


* Nirupama Rao's recco -- Canteloube - "Bailero" sung by Patricia Rozario -- https://www.youtube.com/watch?v=GSqSznrgaSU&feature=youtu.be

* Bill Gates on the Future of Diseases -- http://www.theverge.com/2015/2/25/8103759/bill-gates-interview-hiv-malaria-vaccine-future-disease
- River Blindness - http://en.wikipedia.org/wiki/Onchocerciasis

* WSJ Insiders guide to Delhi -- http://www.wsj.com/articles/insiders-guide-to-delhi-india-1424983405

* (2015, Feb26 - Guardian) -- Black rats wre not the primary caus of the Great Plague of 1347


* (2015 Feb24 - Hindu) - From the first human genome, to a "great library of life" -- http://www.thehindu.com/news/cities/Delhi/from-the-first-human-genome-to-a-great-library-of-life/article6927137.ece
- Lecture at AIIMS by Eric  Lander, leader of the Human Genome Project
- Cost of sequencing - mapping a single genome (as part of HGP 1990-2003) cost $3billion, today it costs $3000
- Global Alliance for Genomics and Health - 246 organisations; 28 countries

* (2015, Feb24, BS) - Waiting for PMs word on GM - On #GMcrops #India - "Regrettably, the sane and well-founded counsel of the scientific community is being largely disregarded." -- http://www.business-standard.com/article/opinion/surinder-sud-waiting-for-the-pm-s-word-on-gm-115022301250_1.html
* (2015, Feb24, BL) - Dangerous Experiments - closure of Astra Zeneca lab, Blr


* Raghuram Rajan on India's Political Economy -- http://scroll.in/article/708502/Full-text:-Invoking-Hitler,-Raghuram-Rajan-warns:-A-strong-govt-may-not-move-in-the-right-direction

* Cool devices -- http://www.wsj.com/articles/interstellar-visual-effects-supervisor-paul-franklins-favorite-gadgets-1424372907
- Digital silence -- Digital Silence DS-101A

* The science of cool design -- http://www.fastcodesign.com/3032932/evidence/the-science-of-cool

* Caravan -- Why India's approach to regulating GM crops is a cause for concern -- http://www.caravanmagazine.in/vantage/why-indias-approach-regulating-gm-crops-cause-concern

* Superbugs -- http://www.livemint.com/Politics/TIs8kQgktJRd6aRi9XLGlO/Superbug-spread-reveals-thin-pipeline-of-newest-antibiotics.html
- Some 16 new antibiotics were approved from 1983 to 1987, but the rate of new drugs coming to market has fallen since then. From 2008 to 2012, just two were approved, according to a study published in the journal Clinical Infectious Diseases.
- While drugmakers charge more than $100,000 for the latest cancer treatments, antibiotics command far less. Cubist Pharmaceuticals Inc., an antibiotic developer bought by Merck & Co. for $8.4b this year, charges between $2,000 and $4,500 for its therapies.
- The Centers for Disease Control and Prevention estimates that each year at least 2 million people are infected with antibiotic-resistant bugs in the US.


* Drone attack in graphics -- https://agenda.weforum.org/2015/02/can-bacteria-affect-our-dna/

* CSS Puns -- http://saijogeorge.com/css-puns/

* Rema on H1N1 Swine Flu -- http://devdutt.com/articles/indian-mythology/celebrating-shivas-holy-night.html
- (2010, ET) -- Did WHO experts fuel swine-flu scare? -- http://articles.economictimes.indiatimes.com/2010-01-13/news/28405023_1_vaccine-manufacturers-arnold-monto-sage

* On Sivaratri - Devdatt Pattnaik -- http://devdutt.com/articles/indian-mythology/celebrating-shivas-holy-night.html

* Mothers - photography -- http://www.jadebeall.com/#!/index/G0000Wm35big.yVE

* What makes You -- http://waitbutwhy.com/2014/12/what-makes-you-you.html

* EMOTIV - story of a bioinformatics co founder - http://www.dailymail.co.uk/news/article-2951852/My-mother-said-captured-pirates-drink-Incredible-story-multimillionaire-CEO-started-life-four-year-old-refugee-fleeing-Vietnam-vial-poison.html

* Obama's pharma deal in India -- http://blogs.timesofindia.indiatimes.com/toi-editorials/obama-versus-obamacare-acting-at-big-pharmas-behest-us-president-hurts-india-others-and-his-own-legacy/

* Idioms - http://blog.ted.com/2015/01/20/40-idioms-that-cant-be-translated-literally/

* Japan's Debt - http://www.bloomberg.com/news/articles/2015-02-10/how-japan-borrows-9-trillion-practically-for-free

* Pronouncing place names correctly -- http://designtaxi.com/news/372514/Useful-Guide-Shows-How-To-Pronounce-The-Tricky-Names-Of-32-Places-Correctly/

* Testosterone Check- http://www.economist.com/news/science-and-technology/21642000-promiscuity-and-fidelity-seem-be-specific-biological-adaptations-their
- The other was of 1,300 people who had had the lengths of their index and ring fingers measured. The ratio of these lengths indicates the effect on an individual of exposure to testosterone in the womb. (A long ring finger compared to the index finger means a big effect.) This ratio corresponds, throughout the primates as a group, to the amount of promiscuity found in a species’s mating system.

* Delhi Elections - the funny side - http://www.newslaundry.com/2015/02/10/the-funny-side-of-delhi-elections/
* Election Tweets - funny - http://www.huffingtonpost.in/2015/02/10/modi-invites-kejriwal-for_n_6649978.html
* Kerjiwal documentary - https://www.youtube.com/watch?v=r3l3RKEBC0M

* 12 Cognnitive Biases -- http://io9.com/5974468/the-most-common-cognitive-biases-that-prevent-you-from-being-rational

* "Encouraged flattery and chamchagiri" - @Ram_Guha takes a dim view of #Indian leaders who set a poor example http://www.ndtv.com/opinion/the-staggering-vanity-of-indias-powerful-737618

* Memory - http://www.newyorker.com/science/maria-konnikova/idea-happened-memory-recollection?intcid=mod-latest

* Farmers, migrant workers - http://www.pri.org/stories/2015-02-04/how-produce-aisle-looks-migrant-farmworker

* Bengal Famine - http://yourstory.com/2014/08/bengal-famine-genocide/

* India -- 28 Reasons Why You Should Never Ever Visit India -- http://www.buzzfeed.com/andreborges/

* Catepillar - Snake Mimicry - http://www.grindtv.com/outdoor/nature/post/caterpillar-appears-snake-camouflage/

* #Polio - how a #Vaccine programe carried on despite "“one of the worst pharmaceutical disasters in U.S. history” - http://www.newyorker.com/news/daily-comment/ike-trusted-new-vaccine

Tuesday, February 24, 2015

H1N1 Swine Flu - The Burden of Import Dependent Diagnosis

(Note: When this piece started out as a prospective op-ed article, the H1N1 death-count was around 650. Today - 18Mar15 -  it has crossed 1800)

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Your child has developed a fever. Could it be Swine Flu? Perhaps it is Bird Flu or Monkey Flu?  

It is difficult not to panic when you have been getting bombarded with daily reports on skyrocketing infections, a rising death toll, shortages of diagnostic kits and medicines.

Unfortunately, our nationwide response to the spread of H1N1 Swine Flu has been just that - reactive rather than proactive. There has been a sudden rush to procure diagnostic kits; an increase the number of ‘authorised outlets’ selling drugs; A DGCI letter to requesting states to ensure that  diagnostic kits and drugs are available at the “right price”, and an awareness campaign that leaves you with more questions than answers.

Meanwhile, the number of deaths has climbed to 1537, and the number of confirmed cases has shot up to over 27,000. The list now includes film stars, top bureaucrats, and senior politicians.

Accurate Diagnosis is the Key

Accurate diagnosis is the first and most critical step in disease control.

For many known diseases the diagnosis and treatment protocols are centred on something called Antigen-Antibody Reactions. Antigens and antibodies are molecules with unique shapes that tend to lock into one another. Antibodies act like policemen in our blood-stream, waiting to ‘handcuff’ any foreign antigens that slip in. Most vaccines contain antigens that provoke our immune systems to produce more antibodies, in case of a real attack. Diseases like measles, for instance, have only one antigenic-type, and this makes the vaccines relatively easy to make, and are therefore quite affordable.

Indian vaccine manufacturers are quite strong in this area. They supply 90 per cent of all measles vaccines worldwide, as well as half of WHO’s requirement for DPT and BCG vaccines against tuberculosis.

Influenza or Flu is caused a much smarter virus. It keeps changing its cell-surface proteins so frequently that detecting it accurately and then formulating drugs to counter them becomes rather difficult.  According to the US Centre for Disease Control there are now more than 800 different influenza viruses. This flu season, the annual influenza vaccine in USA proved only 23% effective. Last year, it was about 60% effective.

When it comes to diagnosis, the only reliable way identifying the flu virus comes from a method called Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR).

Why is RT-PCR Test so Expensive?

RT-PCR is a technique that amplifies genetic material to get a detectable signal. Its accuracy and reliability has made it the cornerstone of modern molecular biology.

The starting point for this test is Deoxyribonucleic acid (DNA), a molecule that encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses.

Despite its unwieldy name, the RT-PCR machine is essentially a hi-tech heater. It ‘melts’ DNA strands at high temperatures and re-joins them again at lower temperatures using special enzymes called polymerases.

Every organism has certain nucleotide sequences which are unique to it. These ‘signature sequences’ are first carefully identified and recreated as “primers”. Detection of H1N1 Swine Flu usually begins with the DNA extracted from a sample of body fluids of an infected person.  It is mixed with H1N1 primers and probes are introduced into a RT-PCR machine.  If the primer finds a match, the machine creates multiple copies of it. Over time – usually 24 hours – there is enough of the genetic material that can be detected by running it through a device called gel chromatograph.

Most of the RT-PCR machines used in India are imported. Apart from the high cost of these machines, the cost of critical consumables - imported primers, probes, enzymes and assays - continue to drive the high cost of accurate diagnosis.  So even the minimum cost for a test comes to about Rs.4,500.

We also have home-grown pioneers like Molbio (Goa) and RAS LifeSciences (Hyderabd) who have developed indigenous, portable PCR kits that lower the cost of the tests to Rs. 800. Despite getting clearances from DCGI and ICMR, the state governments prefer to procure imported kits.

This state of affairs in not unique to diagnostic devices. According to a KPMG report (2011), even though there are about 700 medical device makers in the country, India imports approximately 75 percent of devices.

Is There a Better Way Forward?

Coming soon after the Ebola scare, our tardy response to the H1N1 influenza ought to set the alarm bells ringing.

As the number of nationwide flu-related deaths crosses 1600, we need to ask ourselves if we are sufficiently prepared to tackle the new cohorts of emerging drug-resistant diseases.

We already have world class facilities for manufacture of vaccines and pharmaceuticals. Will the ongoing Budget Session of Parliament introduce the much needed amendments to the Drugs and Cosmetics Act, 1940 – especially with respect to medical devices? Can the on-going ‘Make in India’ initiative pull together the key players in the Government and the private sector, to create the right policy environment for reducing our dependence on expensive, imported diagnostic kits?

Unless we get our act together, we are bound to lurch helplessly from one round of infections and pandemics, to another.
  
REFERENCES

·         DGCI Notice to states - H1N1 / SwineFlu Diagnostic Kits being sold at exhorbitant prices -- http://cdsco.nic.in/writereaddata/swine%20flue.pdf
·         National Centre for Disease Control (NCDC) -- http://www.ncdc.gov.in/
- Procurement of RT-PCR kits -- (11,12) -- http://www.ncdc.gov.in/writereaddata/tenders/160.pdf
·         Dr. Path Labs – List of Molecular Diagnostic Tests - http://www.lalpathlabs.com/genetics.aspx
·         (28Feb15) - http://indianexpress.com/article/india/india-others/swine-flu-deaths-breach-1000-mark-40-more-succumb-to-virus/
·         (9Mar15) - DRDO-RAS diagnostic for SwineFlu -- http://www.thenewsminute.com/news_sections/3181