The Antaki Synthesis (1963): A Foundational Pillar: AstraZeneca, Gilead, and Bristol-Myers Squibb.

Technical Priority of H. Antaki (1951–1963) in Pharmaceutical Scaffolding

The Historical Record: The historical record of medicinal chemistry is anchored by the foundational research of H. Antaki. From 1951 to 1963, Antaki’s peer-reviewed work in the Journal of the Chemical Society (JCS) and the Journal of the American Chemical Society (JACS) established the synthetic frameworks and stability protocols now utilized by the world's leading pharmaceutical innovators.

The Proven Technical Lineage:

• AstraZeneca (formerly ICI): In US Patent 5,258,390, the specification explicitly cites Antaki, J. Chem. Soc., 4877 (1963) as the definitive source for synthetic conditions and as prior art disclosing compounds within the patent's scope for therapeutic acridine-1,8-dione derivatives.

• Gilead Sciences (formerly CV Therapeutics): During the prosecution of US Patent 8,716,319, the USPTO Examiner identified Antaki (1963) as a primary prior art reference for the synthesis of hexahydroquinoline-3-carboxylates.

• Bristol-Myers Squibb: In US Patent 4,122,274, the USPTO Examiner cited the 1958 Antaki JACS findings (vol. 80, pp. 3066–3069) as a critical non-patent citation for the structural baseline of pyrimido-isoquinolinone compounds.

• E.R. Squibb & Sons: In the development of CNS active compounds (US Patent 4,022,897), the USPTO Examiner cited Antaki et al., J. Chem. Soc., pp. 551–555 (1951) as the sole non-patent priority reference.

• Shin Nippon Biomedical Laboratories: In WO2015002150A1, the international filing recognizes Antaki & Petrow, J. Chem. Soc., 1951, pages 551–554 as the primary historical citation for organic cation transporter activity inhibitors.

Conclusion: The "Antaki Synthesis" (1963) remains the original methodology for the catalyst-free isolation of stable 5-oxo-1,4,5,6,7,8-hexahydroquinoline scaffolds. While modern industrial processes have shortened complex 16-step syntheses, the fundamental chemical feasibility of these "Short Processes" rests upon the priority established by H. Antaki.

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The question, why big Pharmaceutical need to burry him?

 

1. The "Materiality" Loophole

Under patent law (specifically 37 CFR 1.56 in the U.S.), applicants only have to disclose information that is "material to patentability." If a company’s legal team decides a document is "cumulative" (meaning it says the same thing as another document already cited) or irrelevant, they aren't legally required to include it.  

• The Strategy: By not citing a document they deem non-material, they avoid "cluttering" the application with information that might distract the examiner or lead to unnecessary clarifying questions.

2. Avoiding "Obviousness" Traps

While a single document might not "anticipate" (directly copy) an invention, it can be combined with others to argue that the invention was obvious.  

• The Risk: Even if Document A doesn't affect the patent on its own, an examiner might combine Document A with Document B to create a "prima facie" case of unpatentability. Companies sometimes omit the "weaker" link in that chain to prevent the examiner from even attempting that combination.  

3. Presumption of Validity

When a patent is granted, it carries a presumption of validity. In future litigation, it is much harder for a competitor to use a piece of prior art to overturn a patent if the patent examiner already looked at it and said, "This doesn't stop the patent."

• The Counter-Strategy: Some companies worry that if they cite too much, the examiner might miss the most dangerous references or perform a "lazy" review. Conversely, if they hold a document back, they might hope a competitor never finds it, or they may feel they have a better chance of explaining it away in court than to a skeptical patent examiner.

4. Administrative "Inundation"

Ironically, some companies do the opposite: they "bury" a key document in a list of hundreds of others. This is called "data dumping."

• The Goal: By citing everything, they technically fulfill their "duty of candor," but they hope the most damaging document is overlooked by an overworked examiner who has only a few hours to review the entire file.

Just some photos South America 2011

The Monkey Orchid

The Dracula Orchid