1988: Back to the human world for a few years

Chapter 441 Cooperation?

It turned out that Yang Mo was a principled man. He said that today's meeting time would only be two hours, and that was two hours.

Therefore, as soon as the clock struck eleven, Suzuki Jiken left the office in a daze, with a mixture of great ecstasy and struggle.

As soon as the old fox left, Zhuo Mali was called to Yang Mo's office.

………………

"Sister Zhuo, how is the progress of your friends' research institutes on the catalytic efficacy of transition cluster ruthenium Ru(II) and the demonstration of industrial production?"

Unlike in the past, Yang Mo seemed very enthusiastic today. As soon as Zhuo Mali entered the office, she was invited to the tea table. Yang Mo even took the initiative to make a cup of Gu Shu Man Zhuan tea for her, which really made her feel flattered.

"Brother, I've been busy with the detailed promotion work for the commercial demonstration zone these days, so I haven't had time to ask. But last week, during their routine report, they did mention that the research and demonstration work on the enantiomeric excess and synthesis yield of transition metal hydrogenation reactions were progressing smoothly. So, I think the research and demonstration work on transition cluster ruthenium (II) should be no problem, right?"

Since Yang Mo used a personal name, Zhuo Mali naturally called him "brother", but the look in her eyes when she looked at Yang Mo was full of awe.

In fact, in the past few years, the research on the efficiency of chiral catalysts has begun to be taken seriously worldwide, and the scientific research community has basically focused on the three major directions of sugars, enzymes, and transition metals.

Replacing rhodium (I) with transition cluster metal ruthenium Ru (II), and using the functional groups in the Ru (II)-BIN-NAP complex molecule to produce hydrogenation reactions with a series of molecules, thereby producing a catalytic effect and achieving extremely high enantiomeric excess and synthesis yield. If this idea was proposed by a researcher specializing in chiral catalysts, it would be fine; but this idea actually came from Yang Mo, a guy who looks like a layman in chemistry, which is really surprising and frightening.

Therefore, since the last trip to Quancheng, when her friends from the research institute, who were originally unhappy, changed from disdain at first, to shock later, and then to reporting their weekly work to her in a respectful tone, and were eager to meet Yang Mo again and listen to the teachings of this great god who was delayed by business, Zhuo Mali, as the coordinator and middleman of this series of work, felt a chill in her back.

Play pig eat tiger!

This is her evaluation of Yang Mo.

As time went by in the group, she felt more and more that Yang Mo was not at all what the outside world thought he was, a lame general with no special talents other than business and strategy.

On the contrary, this guy's knowledge reserves are extremely astonishing, but he always pretends to be a know-nothing uncouth guy in order to confuse others.

She knew very well how terrible this kind of person was.

The other party obviously knows everything and is watching every word and action of his subordinates. It is undoubtedly a ridiculous thing for you to be smart and use your professional knowledge and ability to do tricks and hide it from him. And when he needs to take action, he won't have to go to great lengths to set up a trap for you. He will directly bring out all the mistakes you have concealed in the past, and you will be eliminated in minutes.

A guy with such outstanding abilities and such broad knowledge is so tolerant... How can the people below you survive! ?

Catching the fleeting fear in the eyes of this beautiful girl, Yang Mo smiled helplessly in his heart.

Although the research on efficient chiral catalysts is undoubtedly a shining pearl hanging on the peak of the pharmaceutical industry for people today, in fact, this thing was mentioned in junior high school chemistry in later generations... Of course, in later textbooks, this thing was mainly used to test students' understanding and application of knowledge points such as "mass ratio of material constituent elements" and "mass fraction of material constituent elements".

Unfortunately, the award-winning research results of Dr. Knowles, Professor Ryoji Noza and Professor Sharpless, the winners of the 2001 Nobel Prize in Chemistry, are exactly the content used as case test questions in the junior high school chemistry textbook... and Yang Mo, in his previous life, happened to have read it for some reason.

In the final analysis, he was just a loser who couldn't even recite the periodic table. Apart from some common chemical knowledge that everyone knew, he would fail immediately if you really asked him a question... So this was the reason why, although he valued Zhuo Mali's group of scientific research friends very much, he never dared to meet with them again.

Thinking of this, he sighed silently, but his mouth did not stop: "How is the progress of the research on the catalysis and preparation of the important intermediate (R)-1-propanediol by Ru (II)-BIN-NAP complex?"

Zhuo Mali, who was also not proficient in chemistry, thought about it with some distress, and then answered: "It seems to be going smoothly. Three weeks ago, I completed the experiment of stereoselective reduction of methyl acetoacetate (methyl 2-butyrate) in the laboratory... I remember my friend told me that under the catalysis of Ru (II)-BIN-NAP complex, (R)-2-hydroxy-butyric acid methyl ester was produced by hydrogenation reduction. The yield is very high. In laboratory conditions, it can even reach 97.5%."

Yang Mo nodded: "How is the progress of the experiment on using transition metals to catalyze L-DOPA?"

Zhuo Mali looked a little uneasy. "My friend said that although the direction of this work is fine, it still requires a lot of experiments and comparisons to figure out which functional groups are at work in the asymmetric reduction of the potential chiral compound acetophenone by transition ion chloride, and which substance should be used as a catalyst to form a coordination compound with L-dopa more efficiently."

The implication is obvious. Although chiral catalysis of L-dopaminergic alcohol is possible today, the efficiency is not high, and the enantiomeric excess and synthesis yield cannot meet the needs of large-scale industrial production.

Yang Mo heard this, but there was no disappointment on his face: "What about the research on enzyme catalysis? I don't understand this, but since your friends have been researching it for several years, and I have kept my promise and helped them approve a foreign exchange quota of 150 million US dollars through administrative coordination to purchase various experimental equipment... Now it has been almost three months. According to what they said at the beginning, the research should have made some progress, right?"

Different from transition metal chiral catalysts, Yang Mo actually pays more attention to the research of enzyme catalysis.

The reason is very simple. The series of transition metal chiral catalytic ideas that Yang Mo had given before were actually mainly derived from the research results of Professor Saraji. This professor, who is now teaching in Nagoya, has just completed the industry-university collaborative research on the industrial synthesis of menthol (the flavor component of mint), and then turned his attention to the research of ruthenium catalysts.

So, in essence, under the guidance of Yang Mo, Zhuo Mali's friends were actually conducting research on ruthenium catalysts simultaneously with Professor Saraji... Of course, in terms of progress, Yang Mo was definitely ahead by at least one year with his "latecomer advantage".

But the problem is, leaving aside the fact that this thing was originally the research result of others in history, and Yang Mo has no confidence that he can really reach the finish line before others, using transition metals as chiral catalysts itself has obvious limitations... In most cases, each type of metal chiral catalyst can only react with a few substances. In a sense, this is very characteristic of Western medicine.

But enzyme catalysts are a little different.

This thing not only has high catalytic efficiency and good selectivity, but also relatively mild reaction conditions, and can be widely used in various organic synthesis reactions; therefore, in terms of universality, it is obviously superior to metal chiral catalysts... Not only is it more suitable for China's current national conditions, it is also more in line with his own strategic pace in the pharmaceutical sector.

Zhuo Mali naturally knew how much Yang Mo valued the research on enzyme catalysts. After all, in this era, foreign exchange was an extremely valuable thing. Yang Mo helped her friends coordinate 150 million US dollars in foreign exchange indicators in one go, which was definitely not an easy task... You know, the sponsorship fee for the Asian Games torch relay was only 250 million US dollars.

Thinking of this, Zhuo Mali took a deep breath and said, "Brother, you have repeatedly emphasized this in the past, and you have made great efforts to help them get the foreign exchange index. Therefore, my friends at the enzyme research institute naturally attach great importance to it. They have been working day and night to catch up with the research progress in the past three months. "

"Although the research on enzyme catalysts did not produce results as quickly as the other transition metal catalysts due to the lack of specific reference objects, as the saying goes, diligence can make up for lack of talent. My friends who slept in the enzyme research institute for three months did not disappoint you, brother."

At this point, Zhuo Mali paused, and after carefully recalling it in her mind, she said, "According to last week's work report, the research on ketoreductase, transaminase, imine reductase, hydrolase, and amino acid dehydrogenase, which are enzymes that can be used in chiral catalysis, has made phased progress to varying degrees;"

"Among them, the research progress of oxidoreductase (KRED) is the most gratifying... In the laboratory, ketoreductase has been shown to be able to rely on the coenzyme NADPH or NADH to catalyze redox reactions, and can reduce ketones to corresponding alcohols under mild conditions... My friend has determined that if further research can be carried out, this ketoreductase can be applied to the synthesis research of many chiral alcohol drug intermediates... Especially the synthesis and catalysis of drugs such as statins."

Although scientific research is an extremely serious matter, Zhuo Mali did not dare to exaggerate and just repeated the original words of her friends who worked in the enzyme research institute. However, the excitement and pride on this peach face were visible to everyone.

This is not surprising. Statins are mainstream lipid-lowering drugs and are also one of the drugs with the widest range of applicable populations, the largest sales volume, and the greatest customer stickiness in the world.

In today's era, if we can reduce the cost of statins and improve their efficacy through chiral catalysis, even if they are generic drugs, they will definitely have a terrifyingly huge market prospect. They can even be transformed into original drugs after slight modifications and then dominate the global market.

………………

As expected, upon hearing that there had been a breakthrough in the research on ketoreductase, even though it was still in the laboratory stage, Yang Mo showed an unexpected and delighted smile on his face.

To be honest, although he knew that China had never lacked researchers with skills, strength and attitude, the reason why the number of scientific research results produced for a long time after the reform and opening up was completely incompatible with the scale and volume of China was actually due to the serious shortage of actual scientific research funds and other well-known bullshit, which was not a crime of war;
But he really didn't expect that he had only helped coordinate a mere 150 million US dollars in foreign exchange indicators to help those scientific researchers improve the most basic scientific research hardware and consumables, but in just three months, such gratifying results had been achieved.

Although he himself did not understand technology or scientific research, he once heard a technical elite say when he was a VC in his previous life that enzymes are not quite the same as simple chemical catalysts. As long as you find the right direction, sample one parameter at a time, and try it little by little, you will eventually be able to measure the most suitable enzyme catalyst.

and so……

In fact, it won’t be long before China will have its own chiral enzyme catalysis technology with independent intellectual property rights?
Thinking of this, Yang Mo did not hesitate at all: "Go and communicate with your friends who are doing transition metal catalysis research, and ask them to organize the experimental data parameters. There is no need to involve technical details, and form a general scientific research brief to submit..."

Yang Mo paused halfway through his words, his eyes lingering on Zhuo Mali for a while before he said, "I have reached a preliminary verbal agreement with Sankyo Co., Ltd. We will jointly [develop] transition metal chiral catalyst technology with them in the name of scientific research cooperation. If there are any concrete results, not only can your friends' names be co-signed in the first author column, but the relevant patents will also be shared by the two companies."

"As a price, Sankyo Co., Ltd. agreed to some of my conditions... Sister Zhuo, as the actual contact person and coordinator of this package of work, the subsequent negotiations with Sankyo Co., Ltd. will be left to you!" Zhuo Mali was immediately overjoyed.

Making myself the person in charge of the subsequent negotiations is a reward given because I am very satisfied with my work during this period?
You have to know that once the scientific research really has results and is widely reported by authoritative foreign media, then as the coordinator, you will definitely gain a lot of fame. There are so many benefits behind this!

As expected, my guess was right. Yang Mo, the helmsman, adheres to the principle of clear rewards and punishments!

But after the joy, she had some doubts: "Brother, these chiral catalyst technologies that can be used for large-scale industrial production are great treasures... Is it appropriate to jointly [research and develop] with Sankyo Co., Ltd.?"

As they were all in the underworld, she naturally knew what Yang Mo meant by "joint research and development".

Yang Mo looked a little puzzled. "It's not about whether it's appropriate or not. Sister Zhuo, I just want to ask you a question... Even if we really develop the transition metal chiral catalyst technology one step ahead, given the current situation in our country, is it possible to use it on a large scale?"

Zhuo Mali was stunned for a moment, then smiled bitterly: "I'm afraid it's not very realistic."

Although it may sound unpleasant, the embarrassing reality is that China's domestic pharmaceutical industry is still in a relatively rough primary stage. Thousands of pharmaceutical factories are not only siloed, but also have poor equipment and management. In this situation, they are unable to even mass-produce new generic drugs.
Lack of management, lack of equipment, lack of technical links...you want them to carry out large-scale production of chiral drugs?
Are you kidding!

Yang Mo sighed: "Yes, if it is possible, who would not want to hold all the good things in their own hands? But the reality does not allow it!"

As he spoke, Yang Mo picked up the teacup and took a sip, covering up his slightly lonely expression. "As a comprehensive platform, Dahua has its own mission and responsibility... Over the years, various countries have been intensively conducting research on various EPC synthesis, and according to the news I have received, the research on transition metal chiral catalysts in the island country and America has also entered a critical stage."

"It is foreseeable that within two to three years, the United States and Japan will surely make breakthrough progress in this area of ​​research and commercialize it by relying on their own strong pharmaceutical industrial systems."

"In this case, even if China is the first to achieve results, if we cannot be the first to put them into commercial use, then other than increasing our reputation, it actually has no practical significance... Please remember one thing, if we cannot transform them into commodities on a large scale to conquer the market, such scientific research results will no longer have any value except to be retained as a technical reserve!"

"So, instead of letting the technology these researchers have worked so hard to develop become a collection of sealed files, it is better to share it and maximize the benefits for us."

At this point, Yang Mo smiled and said, "Sister Zhuo, don't forget that the scope of this cooperation is limited to the scope of transition metal chiral catalysts, and enzyme catalysts are not included in it... When we lay a solid foundation with the things we got back, enzyme catalysts with wider applicability will be our real treasure and trump card in the future!"

Yang Mo was not talking nonsense. After 2015, Chinese pharmaceutical companies went overseas on a large scale. On the one hand, this benefited from the greatly enhanced international influence of China. On the other hand, it also benefited from the maturity and application of enzyme catalyst technology… China in later generations is recognized as the king of volume in the world. Any product with mastered technology can be sold at a very low price. And it is obvious that even without considering other factors, with the theoretical support of the spirocyclic ligand skeleton structure, enzyme catalysts have a unique advantage in reducing overall costs.

Although Yang Mo is not willing to engage in a price war unless it is absolutely necessary, but if it is really necessary, Yang Mo actually doesn't mind using this trump card in the field of Western medicine!
Enzyme catalyst?

Zhuo Mali then realized that Yang Mo had been emphasizing the chiral catalyst of transition metals, and had never mentioned the word "enzyme". She pondered for a moment, then asked cautiously, "Brother, can I know the general scope of the cooperation you have reached with Sangong Co., Ltd."

As she spoke, as if she was afraid that Yang Mo would misunderstand her, Zhuo Mali explained: "Since you asked me to be in charge of the subsequent negotiations, I have to have a clear idea in my mind. Otherwise, if I am fooled by others by accident, wouldn't I be a sinner?"

Yang Mo glanced at him and laughed: "Sister Zhuo, you don't need to be so cautious. Since you are already on board, you are my partner. Besides, since I asked you to be responsible for the subsequent negotiations, I naturally can't let you be in the dark."

As he spoke, Yang Mo picked up the purple clay teapot and brewed two cups of tea, sharing them. Then he said leisurely, "I discussed a lot of conditions with that guy Suzuki Jiken, but the most important ones are just these few points:"

"1. Before December of this year, both parties will cooperate on the newly added 12 mu of mulberry fungus cultivation base. The other party's investment, including industrial supporting facilities, cannot be less than 350 billion yen, and we will invest land, technology, personnel, and 1500 million RMB. The equity structure of both parties will be divided according to the previous GAP planting base project case... the same 51%:49%, and the same introduction of the vesting clause."

"2. This [scientific research cooperation] between the two parties must be carried out in the name and mode of industry-university collaboration. If Sankyo Co., Ltd. wants to deeply participate in this research on transition metal chiral catalysts, it must inject 100 billion yen in scientific research funds in three phases;"

"3. Sankyo Co., Ltd. must [share] with us the complete technology and detailed production process of no less than 15 drugs with independent intellectual property rights, including statins, and send a team of engineers to provide hands-on teaching... In short, except for the detailed technology and process of Meperidine (HMG-CoA reductase inhibitor) which are not for sale, the selection of the rest of its drugs will be decided by us!"

"4. According to the agreement, Dezhou is the research site for this cooperation. Therefore, in order to better test the actual effects of various transition metal chiral catalysts in large-scale industrial production, Sankyo Co., Ltd. must invest 6 billion yen in Dezhou before June next year to build at least three pharmaceutical factories with 500-level GMP production workshops... These joint venture pharmaceutical factories will not introduce vesting clauses, and will be invested by Sankyo Co., Ltd., some local pharmaceutical companies reorganized in DZ City, Dahua Company, and Drilling Company!"

Hearing this, Zhuo Mali couldn't help but gasp.

Three pharmaceutical companies with 100,000-level GMP production workshops?
500 billion yen?
Oh my goodness, adding the previous 300 billion and detailed information of a series of drugs, Sankyo Co., Ltd. is bleeding heavily this time!

But more importantly...

Four parties invested?

And it also includes some of the local pharmaceutical companies in DZ City that have been reorganized?
This is clearly an attempt to indirectly influence the ongoing pharmaceutical company restructuring and divestiture work in DZ City, in order to provide bargaining chips for Dahua Company to enter the CXO track in the future!

No, it is not just a bargaining chip for future CXO business, but also to enhance the weight of someone's childhood friend, and then pave the way for the rural grassroots pharmacy chain project advocated by Hu Niu.

Thinking of this, Zhuo Mali vaguely sensed something, and the look she gave Yang Mo became even more inexplicable...

“5. Sankyo Co., Ltd. must fully open its pharmacy channels in the island countries to us, and its channel opening rate must not be lower than 60%. This is my bottom line… In other words, in the future, whether it is our own brand of Chinese patent medicine exported to the island countries or generic drugs exported to the island countries, they must be able to appear on the counters of those pharmacy channels according to this ratio, and we must ensure that there are at least three products, and their display positions cannot be lower than the silver position;”

"Of course, pharmacies are a scarce channel resource in the island country. Although Sankyo Co., Ltd. has a strong influence in this regard, it does not mean that we can do whatever they say. So it is not that we can export as many products as we want. After all, there is a quota for drugs that can enjoy this kind of Class A support... However, as for how many Class A quotas we can get, it depends on your ability at that time, Sister Zhuo."

"6... Forget it. The remaining conditions have nothing to do with this scientific research cooperation and will not be reflected in the subsequent negotiations. So Sister Zhuo, you only need to know the first five conditions and the bottom line."

It was obvious that Mr. Yang, who always wanted to take a bite of the moon when he saw it, had more than just the five conditions mentioned above when negotiating with Suzuki Ciken. However, what the other conditions were was not something that Zhuo Mali could know now.

But even so, Zhuo Mali was frightened: "Brother, your conditions are too many... Can Sankyo Co., Ltd. agree to them?"

Indeed, no matter from which perspective, Yang Mo wanted too much this time, which was obviously beyond the scope of a so-called "scientific research cooperation".

No one is a fool. Faced with so many harsh demands, under normal circumstances, no one would agree.

Yang Mo glanced at this peach and knew that the other party was afraid that if she took these conditions to negotiate with Sankyo Co., Ltd., the negotiations would fail. If the negotiations failed, she would naturally not end up well with Yang Mo.

At the moment he just smiled indifferently.

Indeed, under normal circumstances, no one would agree to so many harsh conditions.

But the problem is... this is not a normal situation right now!
Thinking of this, Yang Mo waved his hand lightly and said, "Sister Zhuo, please feel free to negotiate according to these conditions. I believe Sankyo Co., Ltd. will agree to it in the end."

As he spoke, Yang Mo drank the remaining tea in the cup in one gulp. "Half an hour ago, I just told that guy Suzuki Jiken about the Merck Company in America. If the person sent over to negotiate is not Suzuki Jiken, or if that guy forgets about it... it doesn't matter. I can just bring up Merck again and talk about it. Then those guys should know what to do!"

Zhuo Mali was a little dumbfounded.

Merck of America?
Is this the American pharmaceutical company that China just spent an ultra-low price of 700 million US dollars to get the hepatitis B vaccine from the other party, which was praised by the southern media as "full of humanistic care" and "saved tens of millions of hepatitis B patients in China"?

Could it be...?
She instantly figured out some of the key points, and Zhuo Mali looked at Yang Mo with eyes full of admiration.

As expected, he is the one at the helm. His grasp of timing and scale is second to none...

(End of this chapter)