Prior art — US Patent 9051542

Here is an analysis of the most relevant patent prior art for US patent 9051542, based on the citations within the patent text and considering a current date of April 26, 2026. The priority date for US9051542 is June 1, 2004.

Prior Art Analysis for US9051542

The prior art patents cited in US9051542 are analyzed below for their potential to anticipate the claims of US9051542 under 35 U.S.C. § 102.

1. US4138287A

Full Citation: US4138287A, "Purifying and isolating method for hepatitis virus to use in preparing vaccine", Kjellén, Lars E. (Inventor); Ab Kabi (Assignee).
Publication Date: 1979-02-06.
Brief Description: This patent describes a method for purifying and isolating hepatitis B virus (HBV) antigens from solutions, which involves treatment with a polyanionic substance, a divalent metal salt, and ammonium sulfate. It focuses on isolating virus components, specifically for vaccine preparation, rather than preventing aggregation of viral vectors for gene therapy.
Potential Anticipation: This patent is unlikely to anticipate any claims of US9051542. It deals with HBV, not AAV, and its purification methods are for different viral components (antigens) and purposes (vaccine production). It does not disclose compositions for preventing aggregation of AAV vector particles at high concentrations with specific ionic strengths and multivalent ions as claimed in US9051542.

2. US6194191B1

Full Citation: US6194191B1, "Method for the production and purification of adenoviral vectors", C. Thomas Caskey, Philip C. King, and Michael A. Smith (Inventors); Introgen Therapeutics, Inc. (Assignee).
Publication Date: 2001-02-27.
Brief Description: This patent describes methods for the production and purification of adenoviral vectors, including techniques for harvesting, lysing, and purifying adenovirus. It discusses chromatographic purification and optional ultracentrifugation steps. The focus is on achieving high-titer, pure adenovirus preparations.
Potential Anticipation: This patent is unlikely to anticipate claims of US9051542. While it deals with viral vectors and purification, it is specific to adenoviral vectors, not AAV vectors. The claimed compositions of US9051542 are for AAV, specifying particular ionic strengths, multivalent ions, and concentration ranges that are not disclosed or suggested for adenoviruses in this prior art.

3. US6566118B1

Full Citation: US6566118B1, "Methods for generating high titer helper-free preparations of released recombinant AAV vectors", Patrick L. Hwang, Mary J. W. Rodman, and Thomas C. G. Wong (Inventors); Targeted Genetics Corporation (Assignee).
Publication Date: 2003-05-20.
Brief Description: This patent describes methods for generating high-titer, helper virus-free preparations of recombinant adeno-associated virus (AAV) vectors released from producer cells. It focuses on the release and initial processing, including nuclease treatment and concentration. The goal is to obtain functional AAV preparations with improved yield.
Potential Anticipation: This patent describes methods for AAV production and mentions concentration, which is relevant to US9051542. The abstract and summary do not explicitly disclose the specific formulation components (pH, multivalent ions, specific ionic strength > 200 mM) for storage of AAV to prevent aggregation as required by Claim 1 of US9051542. While it generally discusses high-titer preparations, it doesn't specify the unique solution characteristics claimed. Therefore, it may anticipate the broad concept of high-titer AAV preparations but not the specific compositional elements for aggregation prevention in storage.

4. WO1999061643A1

Full Citation: WO1999061643A1, "Method of preparing recombinant adeno-associated virus compositions by using an iodixananol gradient", Nicholas Muzyczka, John F. Wright, and William W. Hauswirth (Inventors); University Of Florida (Assignee).
Publication Date: 1999-12-02.
Brief Description: This international publication describes a method for preparing recombinant adeno-associated virus (rAAV) compositions using an iodixanol gradient for purification. It focuses on separating AAV from contaminants and empty capsids, which can lead to higher purity and potency.
Potential Anticipation: This patent describes a method for purifying AAV vectors, which results in concentrated compositions. However, its primary focus is on the iodixanol gradient purification method, not on the specific formulation for storage of purified AAV to prevent aggregation at high ionic strength using multivalent ions, as defined in Claim 1 of US9051542. It doesn't disclose the specific ionic strength or excipient components for long-term storage and aggregation prevention.

5. US6146874A

Full Citation: US6146874A, "Method of preparing recombinant adeno-associated virus compositions", Nicholas Muzyczka, John F. Wright, and William W. Hauswirth (Inventors); University Of Florida (Assignee).
Publication Date: 2000-11-14.
Brief Description: This patent is a U.S. counterpart to WO1999061643A1 and describes methods for preparing recombinant adeno-associated virus (rAAV) compositions, particularly emphasizing the use of an iodixanol gradient for purification to achieve high-titer and pure viral stocks.
Potential Anticipation: Similar to WO1999061643A1, this patent focuses on AAV purification methods (specifically iodixanol gradients) to achieve concentrated and pure vectors. It does not detail specific storage formulations with high ionic strength from multivalent ions, a pH between 7.5 and 8.0, and concentrations up to 6.4×10^13 vg/ml specifically to prevent aggregation as defined in Claim 1 of US9051542.

6. US6593123B1

Full Citation: US6593123B1, "Large-scale recombinant adeno-associated virus (rAAV) production and purification", John Fraser Wright (Inventor); Avigen, Inc. (Assignee).
Publication Date: 2003-07-15.
Brief Description: This patent provides methods for large-scale production and purification of recombinant adeno-associated virus (rAAV) using chromatographic techniques, such as ion-exchange chromatography. It aims to achieve high yields and purity suitable for clinical applications. It mentions formulation steps and removal of empty capsids.
Potential Anticipation: This patent, co-invented by John Fraser Wright (also an inventor of US9051542), describes methods for purifying AAV vectors, including concentration and buffer exchange, which are foundational to preparing storage compositions. The patent mentions that purified AAV vectors can be formulated into "suitable pharmaceutical preparations." However, it does not explicitly disclose the specific combination of features recited in Claim 1 of US9051542: i.e., AAV concentrations up to 6.4×10^13 vg/ml, pH between 7.5 and 8.0, excipients with multivalent ions (citrate, sulfate, magnesium, or phosphate), and an ionic strength greater than 200 mM specifically to prevent aggregation. While it sets the stage for high-purity, high-concentration AAV, it lacks the detailed compositional claims for aggregation prevention.

7. US20040166122A1

Full Citation: US20040166122A1, "Adenovirus formulations", Robert K. Evans (Inventor); Evans Robert K. (Assignee).
Publication Date: 2004-08-26.
Brief Description: This patent application describes formulations for adenovirus vectors to improve their stability, particularly with respect to aggregation and degradation. It discusses the use of various excipients, including salts, to maintain stability.
Potential Anticipation: This patent is for adenovirus formulations, not AAV. While it addresses aggregation of viral vectors using excipients, the claims of US9051542 are specific to AAV vectors and their unique aggregation properties and stabilization requirements with particular ionic strength and multivalent ion combinations. Therefore, it is unlikely to anticipate the claims of US9051542. It might, however, be considered relevant for the general problem of viral vector aggregation.

Summary of Potential Anticipation:

The prior art patents primarily focus on the production and purification of either AAV or other viral vectors (adenovirus, hepatitis virus), aiming for high titer and purity. While some discuss the general need for stable formulations, none of them explicitly disclose the specific composition for AAV storage as claimed in US9051542, particularly the combination of:

AAV vector particles at a concentration exceeding 1×10^13 vg/ml up to 6.4×10^13 vg/ml.
A pH buffer with pH between 7.5 and 8.0.
Excipients comprising one or more multivalent ions selected from citrate, sulfate, magnesium, and phosphate.
An ionic strength of the composition greater than 200 mM, specifically to prevent significant aggregation.

Claims 2-6 of US9051542 further define specific embodiments (Pluronic® F68, specific concentrations, particle radius, recovery rates) which are also not explicitly disclosed in the cited prior art. Therefore, while the prior art establishes the general context of AAV production and the problem of viral vector aggregation, it does not appear to directly anticipate the specific solution provided by the claimed compositions in US9051542. The inventive step in US9051542 seems to lie in the specific formulation parameters (high ionic strength > 200 mM using multivalent ions at a specific pH range and AAV concentration) explicitly tailored to prevent AAV aggregation during storage.