IP Library › Granted Patent US 12,491,234
Granted Patent B2
US 12,491,234 · App. 17/041,719 · Granted Dec 9, 2025

Methods and compositions comprising surfactant protein D (SP-D)

Inventors: Jan Susan Rosenbaum (Cincinnati, OH); Mark Cornell Manning (Johnstown, CO); Derrick S. Katayama (Timnath, CO); Giovanni M. Pauletti (Cincinnati, OH); Shawn Grant (Cincinnati, OH); Ryan Holcomb (Cincinnati, OH)
Assignee: Airway Therapeutics, Inc.
A61K38/395A61K9/19A61K47/02A61K47/183A61K47/22A61K47/26
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,491,234
App. No.
17/041,719
Granted
Dec 9, 2025
Kind
B2
Abstract

Some embodiments provided herein relate to methods and pharmaceutical compositions comprising recombinant human surfactant protein D or active fragments thereof. Some such embodiments include solutions or suspensions, and lyophilized solid forms of recombinant human surfactant protein D or active fragments thereof.

Claims (30)

1 . A pharmaceutical composition comprising:

from about 0.1 mg/ml to about 10 mg/ml of a recombinant human surfactant protein D (rhSP-D);

from about 3 mM to about 7 mM of a histidine buffer;

from 200 mM to 300 mM of a sugar, and

from about 0.1 mM to about 10 mM of a calcium salt.

2 . The pharmaceutical composition of claim 1 , wherein the sugar is selected from the group consisting of sucrose, maltose, lactose, glucose, fructose, galactose, mannose, arabinose, xylose, ribose, rhamnose, trehalose, sorbose, melezitose, raffinose, thioglucose, thiomannose, thiofructose, octa-O-acetyl-thiotrehalose, thiosucrose, and thiomaltose.

3 . The pharmaceutical composition of claim 2 , wherein the sugar is lactose.

4 . The pharmaceutical composition of claim 1 , wherein the calcium salt is selected from the group consisting of calcium chloride, calcium bromide, calcium acetate, calcium sulfate, and calcium citrate.

5 . The pharmaceutical composition of claim 4 , wherein the calcium salt is calcium chloride.

6 . The pharmaceutical composition of claim 5 , wherein the concentration of the calcium chloride is from about 1 mM to about 7 mM.

7 . The pharmaceutical composition of claim 1 , having a pH from about 4.0 to about 9.0.

8 . The pharmaceutical composition of claim 7 , having a pH from about 5.5 to about 6.5.

9 . The pharmaceutical composition of claim 1 , wherein the concentration of the rhSP-D is from about 1 mg/ml to about 5 mg/ml.

10 . The pharmaceutical composition of claim 1 comprising a population of rhSP-D polypeptides having oligomeric forms, wherein greater than 30% of the oligomeric forms comprise dodecamers of rhSP-D.

11 . The pharmaceutical composition of claim 1 comprising a population of rhSP-D polypeptides having oligomeric forms, wherein less than 15% of the oligomeric forms comprise aggregates of the rhSP-D, wherein the aggregates have a radius greater than 70 nm.

12 . The pharmaceutical composition of claim 1 , further comprising a bulking agent selected from the group consisting of mannitol, xylitol, sorbitol, maltitol, lactitol, glycerol, erythritol, arabitol, glycine, alanine, threonine, valine, and phenylalanine.

13 . The pharmaceutical composition of claim 1 , wherein the composition lacks a chelating agent selected from EDTA and EGTA.

14 . The pharmaceutical composition of claim 1 selected from the group consisting of:

1 mg/ml rhSP-D, 5 mM Histidine, 265 mM Lactose, 5 mM calcium chloride, wherein the solution has a pH 6.0;

2 mg/ml rhSP-D, 5 mM histidine, 265 mM lactose, 5 mM calcium chloride, wherein the solution has a pH of 6.0;

2 mg/ml rhSP-D, 5 mM Histidine, 265 mM Lactose, 1 mM calcium chloride, wherein the solution has a pH 6.0; and

4 mg/ml rhSP-D, 5 mM Histidine, 265 mM Lactose, 5 mM calcium chloride, wherein the solution has a pH 6.0.

15 . The pharmaceutical composition of claim 1 , wherein the rhSP-D polypeptide comprises the amino acid sequence of SEQ ID NO:02, and wherein the rhSP-D polypeptide has activity in a bacterial aggregation assay or in a TLR4 inhibition assay.

16 . A lyophile of the pharmaceutical composition of claim 1 .

17 . An article comprising a container comprising a lyophile of the pharmaceutical composition of claim 1 .

18 . A method of preparing a lyophile comprising lyophilizing the pharmaceutical composition of claim 1 .

19 . A method of preparing a pharmaceutical composition comprising contacting a lyophile of the pharmaceutical composition of claim 1 with a pharmaceutically acceptable diluent to form a solution or suspension of the rhSP-D.

20 . The method of claim 19 , wherein the diluent is suitable for administration to a lung.

21 . The method of claim 19 , wherein the diluent is sterile water.

22 . The method of claim 19 , wherein the solution or suspension has a concentration of the rhSP-D from about 3 mg/ml to about 5 mg/ml.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2022
From: ROSENBAUM, JAN SUSAN; MANNING, MARK CORNELL; KATAYAMA, DERRICK S.; PAULETTI, GIOVANNI M.; GRANT, SHAWN; HOLCOMB, RYAN
To: AIRWAY THERAPEUTICS, LLC
Reel/Frame 061317/0899 →
CHANGE OF NAME Recorded Oct 5, 2022
From: AIRWAY THERAPEUTICS, LLC
To: AIRWAY THERAPEUTICS, INC.
Reel/Frame 061607/0943 →
Continuity (2)
Provisional Application 62650142 · Mar 29, 2018
Related Publication 20210121536A1 · Apr 29, 2021
References Cited (80)
US 8865643B2 · Clark et al. · 2014 [cited by applicant]
US 9370555B2 · Whitsett · 2016 [cited by examiner]
US 9492503B2 · Whitsett · 2016 [cited by examiner]
US 20110189104A1 · Whitsett et al. · 2011 [cited by applicant]
US 20130316980A1 · Tchirikov · 2013 [cited by applicant]
US 20140302158A1 · Cabrera et al. · 2014 [cited by applicant]
US 20170189527A1 · Rinaldi · 2017 [cited by examiner]
US 20190071693A1 · Rosenbaum et al. · 2019 [cited by applicant]
US 20190071694A1 · Rosenbaum et al. · 2019 [cited by applicant]
EP 1134202A1 · 2001 [cited by applicant]
JP 2001033450A · 2001 [cited by applicant]
JP 2015527402A · 2015 [cited by applicant]
RU 2603093C2 · 2016 [cited by applicant]
RU 2643762C2 · 2018 [cited by applicant]
WO 0180633A2 · 2001 [cited by applicant]
WO 2011017070A1 · 2011 [cited by applicant]
WO WO2012093087 · 2012 [cited by applicant]
WO WO2017143024 · 2017 [cited by applicant]
WO WO2019191254 · 2019 [cited by applicant]
Sarker et al., Lung Surfactant Protein A (SP-A) Interactions with Model Lung Surfactant Lipids and an SP-B Fragment. Biochem. (Jun. 2011), 50(22): 4867-4876. [cited by applicant]
White et al., Increased antiviral and opsonic activity of a highly multimerized collectin chimera. Biochem Biophys Res Commun. (2001) 286: 206-213. [cited by applicant]
Arroyo et al. Structural Characterization of Human Pulmonary Surfactant Protein SP-D by Atomic Force Microscopy. Biophysical J. (2017) 112(3):503a Abstract 2478-Pos. [cited by applicant]
Arroyo et al., Supramolecular Assembly of Human Pulmonary Surfactant Protein SP-D. J Mol Biol. (2018) 430(10):1495-1509. [cited by applicant]
Awasthi S., Surfactant protein (SP)-A and SP-D as antimicrobial and immunotherapeutic agents. Recent Pat Antiinfect Drug Discov. (2010) 5(2):115-123. [cited by applicant]
Clark et al., Structural requirements for SP-D function in vitro and in vivo: therapeutic potential of recombinant SP-D. Immunobiology (2002) 205(4-5):619-631. [cited by applicant]
Clements J.A., Functions of the alveolar lining, Am Rev Respir Dis (1977) 115(6 Pt 2):67-71. [cited by applicant]
Crouch et al., Molecular structure of pulmonary surfactant protein D (SP-D). J Biol Chem. (1994) 269(25):17311-17319. [cited by applicant]
Crouch E.C., Surfactant protein-D and pulmonary host defense. Respir Res. (2000) 1(2):93-108. [cited by applicant]
Crouch et al., Contributions of phenylalanine 335 to ligand recognition by human surfactant protein D: ring interactions with SP-D ligands. J Biol Chem., (2006) 281(26):18008-18014. [cited by applicant]
Debye P., Molecular-weight determination by light scattering. J Phys Chem., (1947) 51:18-32. [cited by applicant]
Dodagatta-Marri et al., Purification of surfactant protein D (SP-D) from pooled amniotic fluid and bronchoalveolar lavage. Methods Mol Biol. (2014) 100:273-290. [cited by applicant]
Griese M., Pulmonary surfactant in health and human lung diseases: State of the art, Eur Respir J (1999) 13:1455-1476. [cited by applicant]
Haagsman et al., Surfactant collectins and innate immunity. Neonatology (2008) 93:288-294. [cited by applicant]
Håkansson et al., Collectin structure: a review. Protein Sci. (2000) 9:1607-1617. [cited by applicant]
Hartshorn et al., Role of viral hemagglutinin glycosylation in anti-influenza activities of recombinant surfactant protein D. Resp Res. (2008) 9(1):65 in 12 pgs. [cited by applicant]
Ikegami et al., Intratracheal Recombinant Surfactant Protein D Prevents Endotoxin Shock in the Newborn Preterm Lamb. Am J Respir Crit Care Med. (2006) 173(12):1342-1347. [cited by applicant]
Kingma et al., Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D. J Biol Chem. (2006) 281:24496-24505. [cited by applicant]
Knudsen et al. A recombinant fragment of human surfactant protein D lacking the short collagen-like stalk fails to correct morphological alterations in lungs of SP-D deficient mice. The Anatomical Record (2009) 292(2):1… [cited by applicant]
Knudsen et al., Surfactant protein D (SP-D) deficiency is attenuated in humanised mice expressing the Met(11)Thr short nucleotide polymorphism of SP-D: implications for surfactant metabolism in the lung. J Anat. (2013) … [cited by applicant]
Korfhagen et al., Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo. J Biol Chem. (1998) 273(43):28438-28443. [cited by applicant]
Malash et al., Association of TLR polymorphisms with bronchopulmonary dysplasia. Gene (2016) 592(1):23-28. [cited by applicant]
Ogasawara et al., The role of the amino-terminal domain and the collagenous region in the structure and the function of rat surfactant protein D. J Biol Chem. (1995) 270(32):19052-19058. [cited by applicant]
Robertson et al., Principles of surfactant replacement, Biochim Biophys Acta (1998) 1408:346-361. [cited by applicant]
Sato et al., Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs. Am J Respir Crit Care Med. (2010) 181(10):1098-1105. [cited by applicant]
Strong et al., A novel method of purifying lung surfactant proteins A and D from the lunglavage of alveolar proteinosis patients and from pooled amniotic fluid. J Immunol Methods. (1998) 220(1-2):139-149. [cited by applicant]
Vieira et al., Structure, Genetics and Function of the Pulmonary Associated Surfactant Proteins A and D: The Extra-Pulmonary Role of These C Type Lectins.Ann Anat. (2017) 211:184-201. [cited by applicant]
Wagner et al., Asymmetric flow field-flow fractionation in the field of nanomedicine. Anal Chem (2014) 86(11):5201-5210. [cited by applicant]
Wert et al., Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. PNAS (2000) 97(11): 5972-5977. [cited by applicant]
White et al., Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus. J Immunol. (2008) 181(11):7936-7943. [cited by applicant]
Winkler et al., Impact of a Met(11) Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model. Exp Lung Res. (2014) 40(4):154-163. [cited by applicant]
Wold et al., PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst. (2001) 58: 109-130. [cited by applicant]
Yamazoe et al., Pulmonary surfactant protein D inhibits lipopolysaccharide (LPS)-inducedinflammatory cell responses by altering LPS binding to its receptors. J Biol Chem. (2008) 283(51):35878-35888. [cited by applicant]
Zhang et al., Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure. J Biol Chem (2001) 276(22):19214-19219. [cited by applicant]
Zimm B.H., The scattering of light and the radial distribution function of high polymer solutions. J Chem Physics (1948) 16(12):1093-1099. [cited by applicant]
Zuo et al., Current perspective in pulmonary surfactant—Inhibition, enhancement and evaluation, Biochim Biophys Acta (2008) 1778:1947-1977. [cited by applicant]
International Search Report and Written Opinion dated Jun. 25, 2019 for PCT/US2019/24305. [cited by applicant]
Hickling, T. et al. “A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory syncytial virus infection in vitro and in vivo.” European Journal of Immunology, vol. 29 Issue 11, 19… [cited by applicant]
Ikegami, M. et al. “Surfactant Protein-D and Surfactant Inhibit Endotoxin-Induced Pulmonary Inflammation.” Chest, vol. 132 No. 5, 2007, pp. 1447-1454. [cited by applicant]
Zbacnik, T. et al. “Role of Buffers in Protein Formulations.” Journal of Pharmaceutical Sciences, vol. 106 No. 3, 2017, pp. 713-733. [cited by applicant]
Stahle, L. et al. “Multivariate Data Analysis and Experimental Design in Biomedical Research.” Progress in Medicinal Chemistry, vol. 25, 1988, pp. 291-338. (Abstract only). [cited by applicant]
Han, Y. et al. “Effects of sugar additives on protein stability of recombinant human serum albumin during lyophilization and storage.” Arch Pharm Res, vol. 30 No. 9, 2007, pp. 1124-1131. (Abstract only). [cited by applicant]
New Jersey Department of Health and Senior Services. Hazardous Substance Fact Sheet: Calcium Hypochlorite, Apr. 2003. Retrieved from https://nj.gov/health/eoh/rtkweb/documents/fs/0323.pdf. [cited by applicant]
Tang, X. et al. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharmaceutical Research, 2004, vol. 21 No. 2, p. 191-200. [cited by applicant]
Schaefers, M. “Reconstructing reconstitution.” Packaging Digest, Dec. 21, 2015. Retrieved from https://www.packagingdigest.com/print/19042. [cited by applicant]
Carpenter, J.F. et al. “Rational Design of Stable Lyophilized Protein Formulations: Theory and Practice.” In Rational Design of Stable Protein Formulations—Theory and Practice, JF Carpenter and MC Manning, eds. Pharmace… [cited by applicant]
Patel, P. et al. “Drug-Excipient compatibility studies: First step for dosage form development.” The Pharma Innovation Journal, 2015, vol. 4, No. 5, pp. 14-20. [cited by applicant]
Brooke, D. et al. “Universal buffers for use in biochemistry and biophysical experiments.” AIMS Biophysics, 2015, vol. 2 No. 3, pp. 336-342. [cited by applicant]
Vuk-Pavlovic, Z. et al. “Carbohydrate recognition domain of surfactant protein D mediates interactions with Pneumocystis carinii glycoprotein A.” Am J Respir Cell Mol Biol, 2001, vol. 24 No. 4, pp. 475-484. [cited by applicant]
Tonnis, W. et al. “Size and molecular flexibility of sugars determine the storage stability of freeze-dried proteins”, Molecular Pharmaceutics, 2015, vol. 12, pp. 684-694. [cited by applicant]
Sako, D. et al. “Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIB.” J Biol Chem, 2010, vol. 285 No. 27, pp. 21037-21048. [cited by applicant]
Bharate, S. et al. “Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review.” Journal of Excipients and Food Chemicals, 2010, vol. 1 No. 3, pp. 3-26. [cited by applicant]
Muller, S. et al. “Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: Results of an early phase II clinical trial.” Arthritis & Rheumatism, 2008, vol. 58 No. 12, pp. 3873-3883. [cited by applicant]
Sorensen, G. “Surfactant Protein D in Respiratory and Non-Respiratory Disesases,” Sec. Pulmonary Medicine. (2018) 5: 1-37. [cited by applicant]
Wong, W. et al., “FungalmelaninstimulatessurfactantproteinD-mediated opsonization of and host immune response to Aspergillus fumigatus spores,” J. Biol. Chem. (2018) 293(13): 4901-4912. [cited by applicant]
Nousheen, L., et. al., “Molecular Docking and Mutational Studies of Human Surfactant Protein-D,” World J. Pharm. Res. (2014) 3(7): 1140-1147. [cited by applicant]
Sim, R. “SP-D,” The Complete FactsBook. (2000): 46-50. [cited by applicant]
Uniprot, Commercially available sequence for recombinant human SP-D. retrieved from https://www.uniprot.org/uniprotkb/P35247/entry#sequences on Oct. 10, 2023. [cited by applicant]
Watson, A. S. “Recombinant Expression of Functional Trimeric Fragments of Human SP-A and SP-D,” University of Southampton, Faculty of Medicine, PhD Thesis (2016). [cited by applicant]
Brown-Augsburger, P. et al. “Site-directed Mutagenesis of Cys-15 and Cys-20 of Pulmonary Surfactant Protein D”. The Journal of Biological Chemistry, vol. 271 No. 23, Jun. 7, 1996, pp. 13724-13730. [cited by applicant]
Zhang, P. et al. “The Amino-terminal Heptad Repeats of the Coiled-coil Neck Domain of Pulmonary Surfactant Protein D Are Necessary for the Assembly of Trimeric Subunits and Dodecamers”. The Journal of Biological Chemist… [cited by applicant]