The entrepreneurship team meet with a patent attorney, Gabriel McCool from Wolf Greenfield. In the meeting, we discussed the patent that was on synthetic heparin, which we had believed was on every type of heparin but was only specific to one avenue of making synthetic heparin. This meant that if we had a different way of making heparin, then we would not perjure the patent and be able to apply for our own, and possibly sell a product in the future.

According to the Court, the laws of nature, physical phenomena, and abstract ideas are not patentable. The relevant distinction between patentable and unpatentable subject matter is between products of nature, living or not, and human-made inventions. (1)

The second requirement for patentability is that the invention be useful. (Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.) The guidelines require that the utility asserted in the application be credible, specific, and substantial. Credible utility requires that logic and facts support the assertion of utility or that a person of ordinary skill in the art would accept that the disclosed invention is currently capable of the claimed use. The utility must be specific to the subject matter claimed and not a general utility that could apply to a broad class of inventions. The substantial utility requires that the invention have a defined real-world use; a claimed utility that requires or constitutes carrying out further research to identify or confirm use in the context of the real world is not sufficient. (1)

Novelty requires that the invention was not known or used by others in this country or patented or described in a printed publication in this or another country before the invention by the patent applicant. The invention must be new to meet the novelty requirement. The statutory bar refers to the fact that the patented material must not have been in public use or on sale in this country or patented or described in a printed publication in this or another country more than one year prior to the date of the application for a U.S. patent. In other words, the inventor may lose the right to a patent if the inventor delays too long before seeking patent protection. An essential difference between the novelty requirement and statutory bars is that an inventor's actions cannot destroy the novelty of his or her invention but can create a statutory bar to patentability.(1)

The test for nonobviousness is whether the subject matter sought to be patented and the prior art is such that the subject matter as a whole would have been obvious to a person having ordinary skill in the art at the time of the invention.(1)

The enablement requirement is directly related to the specification or disclosure. Every patent application must include the specification/disclosure. "The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains...to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.

Enablement encompasses three distinct requirements: the enablement requirement, the written description requirement, and the best mode requirement.

The specification must describe the invention with sufficient particularity that a person with ordinary skill in the art would be able to make and use the claimed invention without "undue experimentation" to satisfy the enablement requirement.

The written description requirement compares the description of the invention set out in the specification with the particular attributes of the invention identified for protection in the claims. It is possible for a specification to meet the test for enablement but fail the written description test. The basic standard for the written description test is that the applicant must show he or she was "in possession" of the invention as later claimed at the time of the application filing. A written description of the specification must support any claim by the inventor.

The inventor violates the best mode requirement where the inventor fails to disclose a preferred embodiment or fails to disclose a preference that materially affects making or using the invention. Suppose that the inventor did contemplate the best mode for practicing the invention. Then, the question becomes whether there was sufficient disclosure of information to enable a person of ordinary skill in the art to practice the best mode of the invention.(1)

To ensure the safety of heparin products in the United States, the FDA asked manufacturers of heparin-containing products to test the heparin active pharmaceutical ingredient (API) used in these products with the two screening methods, capillary electrophoresis (CE) and proton nuclear magnetic resonance (2)

Our beachhead market will be hospitals in the Boston area that are looking for low molecular weight heparin (LMWH) (i.e hospitals who have converted to using enoxaparin as an anticoagulant instead of unfractionated heparin (UFH)) to reduce the risks [1] and variability in efficacy [2] that follow traditional heparin therapy. (5)

‍With the global heparin market being valued at ~9.1 Billion USD [4], we can address that as our TAM. Focusing on the United States, we estimate the SAM to valued at $2.1 Bil USD as the total market for heparin the United States. (5)

‍We estimate target customers to be American hospitals who provide heparin to approximately 12 million patients each year [3]. Consider the ~$1.65 Billion USD American market for LMWH [4]. Since Massachusetts is ~2% of the U.S population we can attribute ~$33 Mil USD ( $1.65 bil × (2 ⁄ 100) to the Massachusetts market. Assuming a high quality biomanufactured LMWH product, one can estimate an initial adoption rate of 5-10% of hospitals in Massachusetts which amounts to a $1.65-3.3Mil USD market share ($33 mil × (10-20 ⁄ 100), representing our SOM. (5)

Our team’s main potential customers are hospitals and pharmacies that need heparin for direct distribution to the customers.Current heparin products are too dependent on the state of cattle and pork. Disease or shortages of either can drastically affect the heparin product, such as the crude heparin crisis. (7)

“Ms. AUTOR. All of their heparin is being stopped and tested. And, again, the contaminated product has been recalled, and the firms that we know that have been affected, that have been associated with contaminated heparin in the U.S., have stopped shipping that contaminated heparin.”
“Mr. Chairman, I find Food and Drug to be the most trusting institution in the world. You folks are more trusting than a kindergarten class. 
Ms. AUTOR. I do not believe, sir, that I would be able to put all heparin coming into the United States on import alert. I do not believe that that would be—— 
Mr. DINGELL. I would be embarrassed,
Mr. Chairman, to come up here and testify this way. I yield back the balance of my time. 
Mr. STUPAK. I thank the gentleman. Mr. Burgess, for questions, please.
Mr. BURGESS. Thank you, Mr. Chairman. A lot of questions are unanswered. Let me just be sure that I understand a couple of things now. To voluntarily test all Chinese imports, you said that’s not occurring at the present time, in response to one of the Chairman’s questions. But all heparin coming into this country is being tested. Those companies are not doing voluntary testing. You referenced some of the compounding practices are perhaps not under voluntary testing. But all heparin coming into this country is currently being tested. Is that correct? 
Ms. AUTOR. Yes, I believe that to be true. 
Mr. BURGESS. Why don’t we just stop heparin active ingredient from coming in from other countries? 
Ms. AUTOR. There are two reasons. One, I think we need to be concerned about potentially causing a shortage of a medically necessary drug. Two—— 
Mr. BURGESS. Now, would that be important for this committee to consider? 
Ms. AUTOR. Absolutely. And, two, under our current legal scheme, I do not believe we have the authority to stop all heparin that’s coming in at the border.”
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“The leading market players are investing significantly in R&D to develop improved formulations and delivery methods, enhancing the effectiveness and safety of heparin products. These efforts aim to address medical needs more efficiently and reduce potential side effects. To tap into new markets and diversify revenue streams, major manufacturers are expanding their geographic presence by establishing distribution networks, manufacturing facilities, and sales operations in emerging markets. Additionally, they are investing in advanced quality control measures, adherence to Good Manufacturing Practices (GMP), and transparency in their supply chains to maintain customer trust and regulatory approval. According to the heparin industry analysis, key players are also forming strategic partnerships with research institutions, healthcare providers, and pharmaceutical companies to advance heparin-based treatments collectively.”(4)

(6)The heparin market share held by each region is displayed in the above picture. While North America does have a chokehold on the heparin market. It also has competitors. Two of North America's most prominent competitors are Europe and Asia Pacific. North America has advanced healthcare infrastructure and regulatory standards that always change with their ongoing advancement. Europe has very deep roots in research, pharmaceutical manufacturing; established companies, and specifying in the production of anti-coagulation in other words heparin. Asia Pacific on the other hand has a very time and cost-saving perspective while also finding news to improve and innovate.

Pfizer: Although Pfizer manufactures its own heparin, it is not their primary anticoagulant. Instead, they prefer ELIQUIS, which “is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, ELIQUIS decreases thrombin generation and blood clot formation.” (8)

Optimvia: Optimvia also creates its own heparin. Their initial business plan was to create synthetic insulin, and they have expanded to synthesizing heparin in a lab. (9)

 June 2023:  Biological E. Limited (BE) received U.S. FDA approval for Enoxaparin Sodium (LMWH) single-dose pre-filled syringes for prophylaxis of deep vein thrombosis in various surgeries and conditions. (4)
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‍August 2022: Malaysia-based Pharmaniaga Berhad collaborated with China’s Suzhou Ronnsi Pharma Co., Ltd. to commercialize halal ovine-derived heparin in Malaysia. March 2022: Hepalink Group announced the approval of heparin sodium and enoxaparin sodium APIs in India with the aim of increasing its distribution channel.(4) 

April 2021: Fresenius Kabi announced two new presentations of Heparin Sodium in convenient, ready-to-administer Freeflex IV bags in the U.S. (4)

‍April 2020: Cerus Advisors DMCC, (CERUS), a boutique family office management firm, announced the acquisition of all of Laboratori Derivati Organici SpA (LDO) by Opocrin S.p.A. stocks. The product portfolio of LDO consists of heparin along with a series of other specialized biological APIs.(4)
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(1)“patent | Wex | US Law | LII / Legal Information Institute.” Law.Cornell.Edu, https://www.law.cornell.edu/wex/patent. Accessed 21 September 2024.

‍(2)“Information on Heparin.” FDA, https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-heparin. Accessed 21 September 2024.

‍(3) Hearing on Climate Change: State and Local Perspectives. U.S. Government Publishing Office, 2007, www.govinfo.gov/content/pkg/CHRG-110hhrg53183/pdf/CHRG-110hhrg53183.pdf. 

‍(4)“Heparin Market Size, Share & Global Forecast Report [2030].” Fortune Business Insights, https://www.fortunebusinessinsights.com/heparin-market-104447. Accessed 21 September 2024. 

‍(5) Solari, F. (2023, August 4). Low-molecular-weight heparin (LMWH). StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK525957/. Accessed 21 September 2024.  

‍(6) Heparin market size, share, and trends 2024 to 2033. Precedence Research. (n.d.). https://www.precedenceresearch.com/heparin-market. Accessed 22 September 2024.

‍(7)professional, C. C. medical. (2024, August 2). Heparin: An enemy of blood clots. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/16017-heparin-infusion. Accessed 22 September 2024.

‍(8)Pfizer statement on publication of Eliquis® Maximum Fair price. Pfizer. (n.d.). https://www.pfizer.com/news/announcements/pfizer-statement-publication-eliquisr-maximum-fair-price#:~:text=About%20ELIQUIS%C2%AE%20(apixaban),generation%20and%20blood%20clot%20formation. Accessed 22 September 2024.

‍(9) Heparin. Optimvia. (n.d.). https://optimvia.com/heparin/
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