Semaglutide – Dr.

Reddy’s
fully synthetic peptide API
In this whitepaper, we look
Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, with 94% sequence homology to at Dr. Reddy’s Semaglutide,
human GLP-1 indicated as an adjunct to diet and exercise to improve glycaemic control in adults a synthetic peptide similar
with type 2 diabetes mellitus [1]. as the innovator that is neither
Our Semaglutide API is a notable example of the technical capabilities of the product development a base nor an acid addition
salt. Hence it is just Semaglutide
team and offers our customers access to a generic API that shows sameness with the innovator only.
product following the US FDA guidelines. We filed our first drug master file (DMF) in August 2021
and have received "Available for reference status" from US FDA by October 2021 with "Zero"
screening deficiency". Furthermore, we offer the product with all necessary data packages -
API characterization and sameness package, and relevant documentation (DMF number 36036,
FEI number 3002949085, completeness assessment done), in accordance with FDA guidelines.

The current* Semaglutide-IP Landscape offers attractive launch

opportunities for formulators

Geography Exclusivity Product Patent

USA NCE-1: December 2021 December 2031 (Including PTE)

Europe DE+ME: February 2028 NCE-1: December 2021

China - March 2026

Brazil - Beyond September 2028*

Japan RE: March 2026 January 2030**

Note: *In Brazil, patent (BRPI0607762A2) is in application stage and if granted the expiry will be 10
years from grant date). **In Japan, PTE applied till 19 January 2030. NCE: New chemical entity; PTE:
Patent term extension; DE- Data exclusivity; ME- Market exclusivity; RE- Re-examination period.

*as per February 2022

Where lies the complexity of Semaglutide?

The active substance Semaglutide is synthetic peptide consisting of 31 amino acids, of which 27 are
L-amino acids, and the remaining (Gly and Aib) are achiral amino acids. In addition, lysine at position 26
is in its derivative form, assembled by attaching a C-18 fatty acid (stearic acid) with two polyethylene
glycol (PEG) and glutamic acid spacers onto the side chain of lysine residue [2].

O
O
OH
HN COOH
O O
H
O N O
N O O NH
H
O

H2N H Aib E G T F T S D V S S Y L E G Q A A E F I A W L V R G R G COOH

N
H
O

Chemical Structure of Semaglutide

 O
O
O
HN COOtBu H2O
O O
H
O N O
N O O NH
H
O

FmocHN COOH

Chemical strcture of Lysine derivatized linker

Synthetic Scheme:

Deprotecting agent
Fmoc-Gly-Wang Resin NH2-Gly-Wang-Resin

1) Fmoc-Arg(Pbf)-OH
2) Fmoc-Gly-OH
3) Fmoc-Arg(Pbf)-OH
Coupling agent, DMF 4) Fmoc-Val-OH
5) Fmoc-Leu-OH
6) Fmoc-Trp(Boc)-OH
7) Fmoc-Ala-OH
8) Fmoc-Ile-OH
Deprotecting agent 9) Fmoc-Phe-OH
10) Fmoc-Glu(OtBu)-OH
11) Lys Derivative linker
Coupling agent,DMF E F I A W L V R G R G COO
Deprotecting agent

12) Fmoc-Ala-OH, 13) Fmoc-Ala-OH

14) Fmoc-Gln(trt)-OH, 15) Fmoc-Gly-OH
16) Fmoc-Glu(OtBu)-OH, 17) Fmoc-Leu-OH
18) Fmoc-Tyr(tBu)-OH, 19) Fmoc-Ser(tBu)-OH
Coupling agent, DMF 20) Fmoc-Ser(tBu)-OH, 21) Fmoc-Val-OH
22) Fmoc-Asp(OtBu)-OH, 23) Fmoc-Ser(tBu)-OH
24) Fmoc-Thr(tBu)-OH, 25) Fmoc-Phe-OH
26) Fmoc-Thr(tBu)-OH, 27) Fmoc-Gly-OH
28) Fmoc-Glu(OtBu)-OH, 29) Fmoc-Aib-OH
30) Boc-His(Boc)-OH,

Global Cleavge, Purification

and Lyophilisation

O
O
OH
HN COOH
O O
H
O N O
N O O NH
H
O
H2O

H2N H Aib E G T F T S D V S S Y L E G Q A A E F I A W L V R G R G COOH

N
H
O

How did Dr. Reddy’s address the challenge?

As for all our processes, an integrated development approach and quality by design (QbD) principles
have been adopted to develop a robust and scalable manufacturing process.

Process AUTHORS

We employ a proprietary technology for solid-phase peptide synthesis of Semaglutide. This

technology is enabled with appropriate process analytical technology (PAT) to provide:

• Consistent high yield and reproducible quality Dr. Rajeev Rehani Budhdev,
• Efficient control of impurities Executive Vice President, Head API R&D
Dr. Reddy's Laboratories.
• High-throughput in terms of batch cycle time

Purification
We used orthogonal purification techniques and separation technologies to purify the peptide and
Alok R Joshi,
obtain the desired critical quality attributes (CQAs). Process analytical tools for chromatography and
Product Manager, Product Management
lyophilization helped optimize the process performance. Dr. Reddy’s Laboratories.

NM Sekhar,
Delivery Manager, Product Development,
Dr. Reddy’s Laboratories.
Analysis and Characterization
Our in-house analysis lab complements our chemistry lab and has high-end capabilities to characterize
the molecule comprehensively and prove its sameness. We applied multiple orthogonal analytical
techniques and tools as part of extensive characterization and impurity profiling.

Manufacturing and Supply Chain Assurance

• We source the amino acid from the world’s leading amino acid manufacturer and have an in-house
source for lysine derivatized side chains

• The current batch size is 600-700 grams, and we are currently scaling up the batch size to 4-5 kg

• The manufacturing facility is equipped with best-in-class peptide synthesizers and purification
technologies, using different separation technologies of various capacities

• Our quality control (QC) labs are equipped with the necessary capabilities to test and release all CQAs

• We can supply customized quantities

How did Dr. Reddy’s cater to Global Formulators?

Dr. Reddy’s provides a unique end-to-end product offering where customers can choose from the
following business models:

• API purchase
• API + device purchase
• Combination of API and Salcaprozpate sodium (SNAC) for oral formulation
• Finished formulations purchase

The partnership a customer forms with Dr. Reddy’s goes beyond the supply of the final product. We
provide our customers with the immunogenicity studies/data available and a complete
characterization data set to cater to regulatory requirements. In addition, our global regulatory affairs
team assists our customers with assembly and filing requirements across various markets.

Disclaimer
The scientific content of this
article has been developed by
Dr. Reddy's Laboratories
Limited ("DRL") for educational
and awareness purpose only.
Although greatest possible
care has been taken in
compiling, checking and
developing the content to
To know more about how we can meet your Semaglutide requirements ensure that it is accurate and
contact us at: api@drreddys.com complete, Dr. Reddy's are not
responsible or liable in the
event of any damages or injury
to any person in view of
reliance placed or action taken
basis of the information in this
article. No part of the article
including graphics available in
this presentation may be
copied or reproduced, in
whole or in part, without the
consent of Dr. Reddy's, other
than for purposes permitted
under fair use by copyright law.

Products protected by valid

References patents are not offered for sale
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434819/ in countries where the sale of
2 https://pubchem.ncbi.nlm.nih.gov/compound/Semaglutide such products constitutes
patent infringement.