API and IP Newsletter

 Contents

• Patent applications filed by Hetero Drugs

• General information

• How To Build a Strong CRO Partnership and Find Drug Development Success?

• FDA Approves First Drug to Treat Hair Loss Caused by Alopecia

• Intellectual Property

• PureCircle Vs Sweegen: Section 112(a) rejection in US by District Court of California.

Patent applications filed by Hetero Drugs

There are many patent applications filed by Hetero Drugs. There are few other IP owners such as Hetero Healthcare, and we combined all IP owners for our analysis. 

A brief of our analysis is as below. 

Publication Number	Abstract (English)	Publication Date	SIDVIM comments
WO2022003585A1	The present invention relates to a transdermal patch composition comprising an active ingredient having anti-inflammatory, analgesic and antipyretic activities. The present invention specifically relates to transdermal patch composition comprising Diclofenac as active ingredient, high concentration of hot melt pressure sensitive adhesive, low concentration of tackifier and pharmaceutically acceptable excipients. The present invention also relates to a process for the preparation of Diclofenac diethylamine transdermal patch	2022-01-06	Hetero is developing diclofenac diethylamine transdermal patch.  Diclofenac epolamine 1/3% patch approved in US in 2018. Hetero might be trying 505 (b) (2) application.
WO2021161206A1	The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R 1, R2, R3, R4, n, and ring (II) are as defined in formula (I). The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.	2021-08-19	NCE work by Hetero. Not much information in public domain about NCE activity of Hetero. It seems it is highly guarded.
WO2021028842A1	The present invention relates to stable ready-to-use injectable formulation comprising Gemcitabine or pharmaceutically acceptable salt as active ingredient, tromethamine as stabilizing and pH modifying agent and other pharmaceutically acceptable excipients which can be infused without any prior dilutions before administration.	2021-02-18	Gemcitabine composition patent application.  There are 3-4 Gx of Gemzar in market, Hetero might be thinking of filing ANDA.
WO2021009595A1	The present invention relates to a stable injectable formulation comprising Cyclophosphamide as active ingredient and pharmaceutically acceptable excipients which is devoid of mannitol. The present invention also relates to methods for the preparation of pharmaceutical compositions of Cyclophosphamide by lyophilization process using solvent and optionally solubilizer wherein lyophilization process does not involve rehydration step.	2021-01-21	Hetero had filed DMF of Cyclophosphamide long ago. Maybe they are in process of filing ANDA. There are only two-three other ANDA holders in the market. Not too much competition for market size of about USD 170 mio/a in the USA. Here.
WO2019207517A1	The present invention provides a process for preparation of deutetrabenazine using tetrabenazine as starting material.	2019-10-31	Deutetrabenazine was approved in 2017 and Hetero already filed DMF in 2020. This must the process Hetero used in their DMF.

Observations:

1. Hetero is filing patent applications which could support their ANDA filings.

2. Hetero, surprisingly, keeping all information about their NCE work on HIV very confidential. In some old report, they mentioned their business strategy is to out-license early-stage discovery molecules and to explore early-stage collaborations as a way of maximising the potential of our research projects. Here

3. Hetero is filing IP around very selective products, protecting deuterium chemistry, protecting patches and overall they have very good IP portfolio.  

General information

How To Build A Strong CRO Partnership And Find Drug Development Success

Selecting the right CRO can be a daunting and arduous process. Here are some criteria to keep in mind when selecting the ideal CRO partner for your organization.

One key consideration is experience and service. It is important to assess the company and staff’s overall experience, but most importantly, their expertise in your therapeutic area. Ask questions about their track record and the results they have delivered. Find out if they have worked on clinical trials at all stages of development, and if they have experience working in the disease indication for which you are developing a treatment. Determining the scope of services that a CRO can provide is equally important. If your company is conducting multiple studies, a CRO with a broad range of services in multiple therapeutic areas may be a good fit. On the other hand, if your trial requires niche expertise, you may be better off with a specialized CRO with experience in fewer therapeutic areas.

News here.

FDA Approves First Drug to Treat Hair Loss Caused By Alopecia

The U.S. Food and Drug Administration (FDA) has approved the drug Olumiant (baricitinib) for adult patients with severe alopecia areata, an immune disorder that often results in hair loss. 

News here.

Intellectual Property 

PureCircle Vs Sweegen: Section 112(a) rejection in US by District Court of California. 

A Section 112 rejection means that certain claim language indefinite. "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed."

Here is the case  PureCircle Vs Sweegen.

Sweegen moved the Court for summary judgment that the '257 patent and '273 patent were invalid and to be rejected as certain claimed features are not disclosed in the specification. Section 112 (a)

Representative claims are as below

Claim 1 of the '257 patent:

1.  A method for adding at least one glucose unit to a steviol glycoside substrate to provide a target steviol glycoside, comprising contacting the steviol glycoside substrate with a recombinant biocatalyst protein enzyme comprising UDP-glucosyltransferase, wherein the target steviol glycoside is Rebaudioside X.

Claim 1 of the '273 patent:

1.  A method for making Rebaudioside X comprising a step of converting Rebaudioside D to Rebaudioside X using a UDP-glucosyltransferase, wherein the conversion of Rebaudioside D to Rebaudioside X is at least about 50% complete.

1. PureCircle accused Sweegen  of infringing `273. 

2. The ’273 Patent is titled “Method for Making Rebaudioside X,” and “relates to a biocatalytic process for preparing compositions comprising steviol glycosides, including highly purified steviol glycoside compositions. 

3. The ’257 Patent is titled “Method of Making Steviol Glycosides,” and has the same specification as the ’273 Patent. 

4. The Asserted Patents are generally directed to a method of making specific kinds of artificial sweeteners or sugar substitutes known as steviol glycosides.

5. Steviol glycosides are naturally occurring chemicals derived from the Stevia rebaudiana plant. 

6. According to PureCircle (patentee), most sweeteners today use a particular kind of steviol glycoside known as “Rebaudioside A” or “Reb A,” “one of the two most prevalent steviol glycosides in the Stevia rebaudiana plant.

7. The Asserted Patents claim a method for making a different steviol glycoside: “Rebaudioside X,” also referred to as “Rebaudioside M” or “Reb M.” 

8. Reb M is a steviol glycoside with a non-sugar core (steviol) and six “glucose” or sugar units. 

9. Figure 1 of the ’273 Patent, depicted below, shows a diagram of the structure of Reb M:

10. According to PureCircle Reb M is a particularly valuable steviol glycoside because it tastes more like sugar than other steviol glycosides, but exists only in trace amounts less than about 0.1% by weight of the total steviol glycoside content in the natural stevia plant, making it difficult and expensive to obtain in commercial quantities. 

11. The Asserted Patents claim to solve this problem by developing new methods for making Reb M using genetic engineering of microorganisms. 

12. The Asserted Patents disclose that Reb M is made by contacting a starting composition comprising a steviol glycoside substrate with UDP-glucosyltransferase thereby producing a composition comprising a target steviol glycoside comprising one or more additional glucose or sugar units than the steviol glycoside substrate.

13. In other words, Patents make Reb M by using UGT enzymes to add sugar units to a steviol glycoside with less than six sugar units until it has six, thereby converting it to Reb M. 

14. Microorganisms, such as yeast or bacteria, are induced to produce the UGT enzymes, which the microorganisms would not normally produce.

15. The District Court considered the issue to be whether the genus of UDP glucosyltransferases (enzyme) was defined and described structurally or functionally and, deciding it was the latter, found that the claims did not provide adequate written description support.  

16. The Court held, precedent requires a showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus, or structural features common to the members of the genus so that one of skill in the art can visualize or recognize the members of the genus

17. There is no dispute between the parties that the specification does not expressly disclose structural features common to all UGT enzymes having the recited function. 

18. in fact only 4 UGT enzymes are disclosed (UGT76G1, UGT91D2, UGT91D2e, and UGT91D11) and the specification further states that the particular UDP-glucosyltransferase used in each reaction can either be the same or different, depending on the particular site on the steviol glycoside substrate where glucose is to be added.

19. Amino acid sequence comparisons was provided in specifications, but the Court was not impressed. 

20. The Court said an enzyme's amino acid sequence does not necessarily predict the enzyme's activity (or functionality) and, therefore, testing is always required to determine the enzyme's activity (or functionality)," from which the Court concluded that "two enzymes with the similar sequences can have different functions and two enzymes with very different sequences can have the same function.

21. But here, the Court found that a comparison of two of the disclosed UDP-glucosyltransferases (UGT76G1 and UGT91D2) did not disclose common structural features sufficient to satisfy the requirement for an adequate written description.  

22. Finally, the District Court found that as of the filing date common structural features between different UDP-glucosyltransferases were not known in the art (and what features that were known were not universally associated with UDP-glucosyltransferase function).  

23. Accordingly, the District Court granted Sweegen's motion that all claims were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a).

Patent drafting sometimes becomes most critical and defining each feature is important. Here.