US 12031894

Here's a concise summary of US patent 12031894:

US Patent 12031894

• Title: Analytical ultracentrifugation for characterization of recombinant viral particles
• Assignee: Genzyme Corp [cite: The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.]
• Inventors: Catherine R. O'Riordan, Brenda BURNHAM
• Filing Date: 2023-11-20
• Issue Date: 2024-07-09
• Abstract: Provided herein are methods to characterize preparations of recombinant viral particles using analytical ultracentrifugation. Recombinant viral particles include recombinant adeno-associated viral particles, recombinant adenoviral particles, recombinant lentiviral particles, and recombinant herpes simplex virus particles. Variant species of recombinant viral particles including empty capsids and recombinant viral particles with variant genomes (fragmented genomes, aggregates, recombinants) can be identified and quantitated. The methods can be used to characterize preparations of recombinant viral particles regardless of the sequence of the recombinant viral genome or the serotype of the recombinant viral capsid.

Plain-Language Overview of Independent Claims:

• Claim 1: This claim describes a method for characterizing a preparation of recombinant viral particles. It involves subjecting the preparation to analytical ultracentrifugation (AUC) under boundary sedimentation velocity conditions, monitoring the sedimentation of the viral particles at intervals, plotting the differential sedimentation coefficient distribution value (C(s)) against the sedimentation coefficient in Svedberg units (S), and then integrating the area under each peak in the C(s) distribution to determine the relative concentration of each peak. Each peak represents a distinct species of recombinant viral particle.
• Claim 2: This claim pertains to a method for assessing the integrity of the vector genome within recombinant viral particles. It includes steps similar to Claim 1 (AUC, monitoring, plotting C(s) vs. S) and further specifies identifying different species of viral particles by their S values. The genome size of a species is calculated by comparing its S value to a standard curve derived from viral particles with known genome sizes.
• Claim 3: This claim outlines a method to detect the presence of empty capsids or capsid particles containing variant-sized recombinant viral genomes. The method involves AUC, monitoring, and plotting C(s) vs. S. The presence of one or more peaks other than the peak corresponding to full capsid particles (those with intact recombinant viral genomes) indicates the presence of either variant-sized genomes or empty capsids.
• Claim 4: This claim details a method for measuring the relative amount of empty capsids in a preparation. It involves AUC, monitoring, plotting C(s) vs. S, and integrating the area under each peak to determine relative concentrations. Subsequently, the amount of viral particles with an S value characteristic of empty capsids is compared to the amount of particles with intact viral genomes or to the total amount of recombinant viral particles in the preparation.
• Claim 5: This claim describes a method for measuring the relative amount of capsid particles containing variant recombinant viral genomes or empty viral capsid particles. The steps include AUC, monitoring, plotting C(s) vs. S, and integrating peak areas to determine relative concentrations. The amount of viral particles with S values not corresponding to intact genomes is then compared to the amount of particles with intact genomes or to the total amount of recombinant viral particles.
• Claim 6: Similar to Claim 5, this claim focuses on measuring the relative amount of capsid particles containing variant recombinant viral genomes. It follows the same AUC, monitoring, plotting, and integrating steps. The comparison is made between the amount of viral particles with S values not corresponding to intact genomes or empty capsids, and the total amount of recombinant viral particles.
• Claim 7: This claim provides a method for measuring the relative amount of recombinant viral particles comprising intact viral genomes. It involves AUC, monitoring, plotting C(s) vs. S, and integrating peaks. The amount of particles with S values corresponding to intact viral genomes is then compared to the amount of empty capsids, to capsid particles with variant genomes, and/or to the total amount of recombinant viral particles.
• Claim 8: This claim describes a method for monitoring the removal of empty capsids and/or variant-genome-containing capsids during the purification of recombinant viral particles. It involves taking a sample after one or more purification steps and analyzing it using the methods of claims 5-8 (as recited in the patent, likely referring to the measurement claims). A decrease in the relative amount of empty capsids and/or variant-genome-containing capsids relative to full capsids indicates successful removal.
• Claim 9: This claim focuses on methods for evaluating a process for the production of recombinant viral particles. It utilizes the methods of claims 1 to 31 (as recited in the patent, broadly referring to the characterization and measurement methods). An increase in the relative amount of intact-genome-containing particles compared to empty capsids and/or variant-genome-containing particles, when compared to a reference preparation, signifies an improvement in the production process.
• Claim 10: This claim provides a method for preparing recombinant viral particles with reduced empty capsids and/or variant-genome-containing particles. It involves culturing host cells with specific nucleic acids (heterologous transgene flanked by ITR, AAV rep and cap coding regions with a p5 promoter, and AAV helper virus functions), lysing cells, isolating particles, and then analyzing for empty capsids and/or variant genomes using the analytical ultracentrifugation methods described in the patent.
• Claim 11: This claim is a specific refinement of Claim 10, detailing a method for preparing recombinant viral particles with reduced empty capsids and/or variant genomes by utilizing a mutated p5 promoter in the nucleic acid comprising AAV rep and cap coding regions, where expression from this promoter is reduced compared to a wild-type p5 promoter. The subsequent steps of lysing, isolating, and analyzing are the same as in Claim 10.

USPTO and CAFC Dockets:

• USPTO: Information for US12031894B2 was accessed via Google Patents, which aggregates data directly from patent offices, including the USPTO. Direct real-time searching of USPTO dockets for this specific patent number was not performed, as the Google Patents entry is considered authoritative for the core patent details.
• CAFC Dockets (2026): A direct search of CAFC 2026 dockets for patent number 12031894 did not yield specific results. However, the Google Patents page for US12031894B2 notes the following related litigation: "PTAB case IPR2026-00150 filed (Pending)" [cite: Status, Critical]. This indicates ongoing patent validity proceedings at the Patent Trial and Appeal Board (PTAB) for this patent family.

As a patent attorney, I have identified the following known litigation involving US patent 12031894:

Patent Trial and Appeal Board (PTAB) Case:

• Case Number: IPR2026-00150
• Plaintiff(s): Petitioner (not explicitly named in the provided snippets)
• Defendant(s): Genzyme Corporation et al. (Patent Owner/Respondent)
• Jurisdiction: Patent Trial and Appeal Board (PTAB) of the USPTO
• Filing Date: Not explicitly stated in the provided snippets, but the Decision Issue Date is May 6, 2026.
• Outcome or Current Status: Institution Granted.

Proceedings overview

There is one AIA trial proceeding on file for US patent 12031894. This proceeding, IPR2026-00150, has been instituted for trial and is currently active. The institution of trial against a significant number of claims indicates that the PTAB found a reasonable likelihood of Sarepta Therapeutics, Inc. et al. prevailing, which presents a significant challenge to the patent's validity.

IPR2026-00150 — Sarepta Therapeutics, Inc. et al. v. Genzyme Corporation et al.

• Type: Inter Partes Review
• Filed: 2025-11-25
• Status: Trial Instituted. The PTAB has decided to move forward with a trial on the challenged claims. The status was last modified on 2026-05-20.
• Judge panel: The institution decision was made by USPTO Director John A. Squires, consistent with the new policy effective October 20, 2025, where the Director decides whether to institute IPRs. The specific Administrative Patent Judge panel for the ongoing trial phase has not been publicly identified in the available information.
• Petition grounds: Sarepta challenged claims 1-7 and 10-30 of U.S. Patent No. 12,031,894. The petition argues that these claims are unpatentable as obvious under 35 U.S.C. § 103, based on the prior art references Le Bec, de la Maza, Sommer, and Cole.
• Institution decision: Instituted on 2026-05-06. The Director granted institution on the merits, determining that the petition demonstrated a reasonable likelihood that at least one challenged claim is unpatentable.
• Final Written Decision (if issued): Not yet issued. The trial is ongoing.
• Settlement / termination: Not applicable at this stage.
• Appeal: Not applicable at this stage, as no Final Written Decision has been issued.
• Defensive value: The institution of trial means that a significant portion of the patent's claims (claims 1-7 and 10-30) are currently under review for obviousness. If the claims are ultimately canceled, any infringement theory relying on them would be severely undermined. For now, the patent's validity is actively being challenged, which could influence litigation strategy.

Strategic summary

As of the current date, only one AIA trial proceeding, IPR2026-00150, has been filed and instituted against US patent 12031894. Claims 1-7 and 10-30 are currently under active review at the PTAB. No claims have been definitively canceled or sustained by a Final Written Decision. Therefore, all claims currently remain legally active, but their patentability is being challenged.

The estoppel landscape under 35 U.S.C. § 315(e)(2) will only fully develop upon the issuance of a Final Written Decision. If Sarepta (and its privies) were to receive an unfavorable FWD on any of the challenged claims, they would be estopped from asserting invalidity on any ground that was raised or reasonably could have been raised during the IPR. For other potential defendants, however, these prior art grounds (Le Bec, de la Maza, Sommer, and Cole for obviousness) may still be available unless they are in privy with Sarepta or otherwise estopped.

Regarding pattern signals, this is the first IPR filed against US12031894. It was filed by Sarepta Therapeutics, Inc. et al., which is also involved in ongoing district court litigation (Case No. 1:24-cv-00882, D. Del.) where Genzyme has asserted this patent. This suggests the IPR is a defensive maneuver in response to that litigation. The fact that institution was granted by Director Squires, who recently took over institution decisions and has introduced new factors, is noteworthy.

Recommended next steps

For a defendant facing assertion of US12031894, the ongoing IPR2026-00150 is a critical development. Since the trial was instituted on 2026-05-06, a Final Written Decision is statutorily due approximately one year later, around 2027-05-06. It is advisable to closely monitor the progress of IPR2026-00150 for any developments, particularly the issuance of the Final Written Decision, which will determine the patentability of claims 1-7 and 10-30. The institution decision can be accessed via the USPTO Open Data Portal.

Inventors

• Catherine R. O'Riordan (Genzyme Corp)
• Brenda BURNHAM (Genzyme Corp)

No unusual patterns detected based on the provided information.

Original assignee

Genzyme Corp. is the original assignee. Genzyme Corp. is a biotechnology company that develops and manufactures products for rare diseases. While the patent describes methods for characterizing recombinant viral particles, it is unclear from the patent text alone whether Genzyme Corp. directly shipped a product embodying the claims (i.e., a commercial product for performing analytical ultracentrifugation for viral particle characterization). Their primary line of business is biotechnology, focusing on therapeutics for rare diseases. Genzyme Corp. was acquired by Sanofi in 2011 and operates as a subsidiary.

Assignment timeline

• 2023-11-30 (executed) / recorded 2023-11-30 — Reel 059952/0130
  • Conveyance: Assignment of Assignors Interest
  • Assignor: O'RIORDAN, CATHERINE; BURNHAM, BRENDA
  • Assignee: GENZYME CORPORATION
  • Correspondent: Bjoern Staschen, Sanofi, 50 Binney Street, Cambridge, MA 02142
  • Context: Internal transfer from inventors to corporate assignee

Timeline diagram

timeline
    title Ownership of US 12031894
    2015 : Priority date
    2023 : Application filed
    2023 : Inventors assign to Genzyme Corp
    2024 : Granted

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The transfer is from individual inventors to Genzyme Corporation, a known operating company.
2. Known asserter in the chain — not present. Genzyme Corporation is not a known NPE.
3. Repeat correspondent across the chain — not present. Only one assignment is recorded, so no recurrence can be observed. The correspondent, Bjoern Staschen from Sanofi, is associated with the operating company Genzyme Corp.
4. Cascading transfers — not present. Only one assignment is recorded.
5. Pre-litigation transfer — unclear. While there is litigation mentioned in Google Patents ("Family has litigation," "PTAB case IPR2026-00150 filed (Pending)"), the specific filing date for the first infringement suit is not provided in the patent text or immediate search results. The only assignment record (2023-11-30) precedes the patent grant (2024-07-09).
6. Bankruptcy fire-sale — not present. Genzyme Corp. was acquired by Sanofi, not dissolved or in bankruptcy.
7. Privateering — not present. No evidence of an operating company transferring to an NPE for assertion.
8. Defensive aggregator (anti-NPE) — not present. The current assignee is Genzyme Corp., an operating company.

Verdict

Insufficient data. Only one assignment from the inventors to the original assignee (Genzyme Corporation) is recorded at the USPTO Assignment Center. This is a standard initial assignment and does not provide enough information to identify NPE or patent-troll patterns.

Verification: https://assignmentcenter.uspto.gov/ (Search for patent number 12031894).

US patent 12031894 is titled "Analytical ultracentrifugation for characterization of recombinant viral particles." [cite: The patent text provided in the prompt states that the patent number US12031894B2 is for "Analytical ultracentrifugation for characterization of recombinant viral particles." This is directly from the patent title.] It was granted on July 9, 2024, with a filing date of November 20, 2023. [cite: The patent text provided in the prompt includes a "Publication date" of "2024-07-09" and a "Filing date" of "2023-11-20" for US12031894B2.]

To identify the most relevant prior art, I would typically perform a detailed search of the cited references within the patent itself and then potentially broaden the search to include other related patents and non-patent literature. However, since the request specifically asks to look at each patent citation for 12031894, I will focus on the references explicitly listed in the patent document.

Upon reviewing the provided patent text for US12031894B2, the "CROSS-REFERENCE TO RELATED APPLICATIONS" section lists the following related U.S. patent applications, which are incorporated by reference in their entirety [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", lists these applications and states they are "incorporated herein by reference in their entirety."]:

• U.S. patent application Ser. No. 18/188,176

  • Publication/Filing Date: March 22, 2023 [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", states "filed Mar. 22, 2023".]
  • Brief Description: This is a continuation of U.S. patent application Ser. No. 16/547,144. It generally concerns methods for characterizing recombinant viral vectors using analytical ultracentrifugation.
  • Potential Anticipation: As a direct continuation, this application would cover similar subject matter and could potentially anticipate all claims of US12031894 under 35 U.S.C. § 102, depending on the specific claims and any new matter introduced in 12031894.

• U.S. patent application Ser. No. 16/547,144 (now U.S. Pat. No. 11,639,887)

  • Publication/Filing Date: August 21, 2019 [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", states "filed Aug. 21, 2019".]
  • Brief Description: This is a continuation of U.S. patent application Ser. No. 15/544,498. It generally concerns methods for characterizing recombinant viral vectors using analytical ultracentrifugation. [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", indicates it's a continuation and its title likely aligns with the general subject matter.]
  • Potential Anticipation: As a parent application that matured into U.S. Pat. No. 11,639,887, this would cover highly similar subject matter and could potentially anticipate all claims of US12031894 under 35 U.S.C. § 102, depending on the specific claims and any new matter introduced in 12031894.

• U.S. patent application Ser. No. 15/544,498 (now U.S. Pat. No. 10,429,288)

  • Publication/Filing Date: Adopted international filing date of January 19, 2016 [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", states "which adopts the international filing date of Jan. 19, 2016".]
  • Brief Description: This is a National Phase application of International Application No. PCT/US2016/013947 and claims priority to U.S. Provisional Application No. 62/105,714. It generally concerns methods for characterizing recombinant viral vectors using analytical ultracentrifugation.
  • Potential Anticipation: As a direct parent application that matured into U.S. Pat. No. 10,429,288 and claims priority back to January 20, 2015, this would be highly relevant prior art and could potentially anticipate all claims of US12031894 under 35 U.S.C. § 102, depending on the specific claims and any new matter introduced in 12031894.

• International Application No. PCT/US2016/013947

  • Publication/Filing Date: January 19, 2016 [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", states "filed Jan. 19, 2016".]
  • Brief Description: This PCT application claims priority to U.S. Provisional Application No. 62/105,714 and covers the same general subject matter of analytical ultracentrifugation for characterizing recombinant viral particles.
  • Potential Anticipation: As a PCT application with an early filing date and claiming priority to a provisional application, this would be significant prior art and could potentially anticipate all claims of US12031894 under 35 U.S.C. § 102, depending on the specific claims and any new matter introduced in 12031894.

• U.S. Provisional Application No. 62/105,714

  • Publication/Filing Date: January 20, 2015 [cite: The full patent text, under "CROSS-REFERENCE TO RELATED APPLICATIONS", states "filed Jan. 20, 2015".]
  • Brief Description: This is the earliest priority document mentioned and would contain the foundational disclosure for the invention relating to analytical ultracentrifugation for characterizing recombinant viral particles.
  • Potential Anticipation: As the earliest priority document, this provisional application is critical prior art. It could potentially anticipate all claims of US12031894 under 35 U.S.C. § 102, assuming the claims are fully supported by the disclosure in this provisional application.

Beyond these related applications in the family, the patent also makes general references to other U.S. patents and publications within the detailed description and definitions, such as U.S. Pat. No. 6,566,118 [cite: The full patent text, under "Suitable media known in the art", mentions "U.S. Pat. No. 6,566,118".], U.S. Pat. Nos. 5,622,856; 6,001,650; 6,027,931; 6,365,403; 6,376,237; and 7,037,713 [cite: The full patent text, under "the nucleic acid encoding AAV rep and cap coding regions", mentions these patent numbers.], U.S. PG Pub. 2012/0164106 [cite: The full patent text, under "the rAAV particles", mentions "U.S. PG Pub. 2012/0164106".], U.S. Pat. No. 8,283,151 [cite: The full patent text, under "an AAV2 N587A capsid", mentions "U.S. Pat. No. 8,283,151".], and International Publication No. WO/2003/042397 [cite: The full patent text, under "an AAV2 N587A capsid", mentions "International Publication No. WO/2003/042397".]. To fully assess their relevance as prior art, a detailed analysis of each of these specific patents and publications would be required, including their claims and disclosures, to determine which specific claims of US12031894 they might anticipate. Without accessing the full text of these individual references and comparing them claim-by-claim to US12031894, a definitive statement of anticipation for specific claims cannot be made.

However, based on the provided text, the most directly relevant prior art under 35 U.S.C. § 102 would be the parent applications and the provisional application because they disclose the same or highly similar inventive concepts and have earlier effective filing dates. Specifically, claims 1-31 of US12031894, which describe the core method of characterizing recombinant viral particles using analytical ultracentrifugation and the subsequent analysis, would be most likely anticipated by the earlier filings that share the same inventive subject matter. For instance, the general method described in claim 1 of US12031894 ("A method of characterizing a preparation of recombinant viral particles comprising the steps of a) subjecting the preparation to analytical ultracentrifugation under boundary sedimentation velocity conditions wherein the sedimentation of recombinant viral particles is monitored at time intervals, b) plotting the differential sedimentation coefficient distribution value (C(s)) versus the sedimentation coefficient in Svedberg units (S), and c) integrating the area under each peak in the C(s) distribution to determine the relative concentration of each peak, wherein each peak represents a species of recombinant viral recombinant viral particle.") appears to be broadly covered in the description of the invention in the earlier-filed applications.

US patent 12031894B2, titled "Analytical ultracentrifugation for characterization of recombinant viral particles," describes methods for characterizing preparations of recombinant viral particles using analytical ultracentrifugation (AUC) under boundary sedimentation velocity conditions. The invention focuses on monitoring sedimentation, plotting the differential sedimentation coefficient distribution value (C(s)) versus the sedimentation coefficient in Svedberg units (S), and integrating peak areas to determine the relative concentration of different species of recombinant viral particles. These species can include full recombinant viral particles with intact genomes, empty capsids, and variant viral particles containing fragmented genomes, aggregates, or DNA impurities. The methods are stated to be applicable to recombinant adeno-associated viral (rAAV) particles, recombinant adenoviral (rAd) particles, recombinant lentiviral particles, and recombinant herpes simplex viral (rHSV) particles.

The patent aims to provide a generic assay for characterizing recombinant viral preparations, independent of the viral genome sequence or capsid serotype, addressing a perceived need for improved analytical methods beyond traditional techniques like Southern blot and immunoassays.

Obviousness Analysis under 35 U.S.C. § 103

A person having ordinary skill in the art (PHOSITA) in 2015, the priority date of US12031894B2, would have found the claimed methods obvious in light of existing prior art, particularly the disclosure of analytical ultracentrifugation for characterizing adenovirus preparations and the common knowledge regarding the versatility of AUC.

Prior Art References:

1. Berkowitz, S A & Philo J S, (2007) Anal. Biochem., 362:16-37: This publication is explicitly cited in US12031894B2 and teaches the "Use of analytical ultracentrifugation to characterize adenovirus preparations".
2. Schuck (2000) Biophys. J., 78:1606-19: This reference describes the SEDFIT algorithm, which utilizes Lamm equation solutions for analyzing hydrodynamic data such as sedimentation velocity. The present patent acknowledges that C(S) values are determined by algorithms comprising Lamm equation solutions, specifically mentioning SEDFIT.
3. Cole et al. (2008) Methods Cell Biol., 84:143-79: This publication provides general methods for optically detecting a sedimenting boundary and measuring its rate of movement or migration in AUC.
4. Furst (1997) Eur. Biophys. J. 35:307-10: This reference describes the use of Rayleigh interference optics with AUC.
5. General Knowledge in the Art regarding Gene Therapy Vectors and AUC Principles: The patent itself cites numerous references illustrating the widespread use and understanding of rAAV, rAd, lentivirus, and rHSV in gene therapy applications, as well as various production and purification methods for these vectors (e.g., Conway, J E et al., (1997) J. Virology 71(11):8780-8789; Danthinne, X. and Imperiale, M. J. (2000) Gene Ther. 7:1707-14; Tatsis, N. and Ertl, H. C. (2004) Mol. Ther. 10:616-29; Thorne et al. (2009) Hum. Gene Ther., 20:707-14). The fundamental principles of AUC, including its ability to resolve different particle species based on molecular weight and shape, were well-established.

Combinations and Rationale for Obviousness:

The primary claims of US12031894B2 revolve around applying established AUC techniques to characterize various recombinant viral particles. This would have been obvious to a PHOSITA by combining the specific teaching of Berkowitz & Philo (2007) with the general knowledge in the field of virology and biophysical characterization.

Combination 1: Berkowitz & Philo (2007) + General knowledge in the art (including Schuck (2000), Cole et al. (2008), Furst (1997), and knowledge of various viral vectors)

1. Disclosure by Berkowitz & Philo (2007): This reference clearly teaches the application of AUC for the characterization of adenovirus preparations. Characterizing viral preparations using AUC inherently involves monitoring sedimentation, plotting C(s) versus S (or equivalent distributions), and identifying different particle species based on their sedimentation coefficients, such as empty versus full capsids, aggregates, or fragments. These are standard analytical outputs of AUC sedimentation velocity experiments.
2. Motivation to Combine/Apply to Other Viral Particles:
   • Known Versatility of AUC: As explicitly stated in US12031894B2, "AUC analysis has been well characterized over many decades and is highly versatile. Because AUC analysis relies upon first-principle hydrodynamic and thermodynamic information, AUC may be applied to determine the biophysical properties of many types of particles across a wide range of particle concentrations and sizes". A PHOSITA would recognize AUC as a broadly applicable technique for macromolecule characterization.
   • Common Need for Characterization: The background of US12031894B2 highlights the ongoing need for robust analytical methods to monitor the quality of recombinant viral vectors (including rAAV, lentivirus, and rHSV) for gene therapy applications, particularly regarding homogeneity, purity, and consistency of manufacturing. Existing methods like Southern blots and immunoassays were recognized as having limitations. Faced with the problem of needing a generic and comprehensive characterization method for various viral vectors, a PHOSITA would naturally consider applying a powerful biophysical technique already shown useful for one type of viral vector (adenovirus, per Berkowitz & Philo) to other similar viral systems.
   • Predictable Results based on Viral Sizes: US12031894B2 itself provides a strong rationale for extending the method: "Without wishing to be bound to theory, a range of AUC settings that allows the analysis of both AAV and adenovirus particles should enable the analysis of other viral particles including lentivirus and HSV since the size of HSV and lentiviral particles is between that of AAV and adenovirus particles". This statement effectively describes the expectation of a PHOSITA – that a method successful for adenovirus could be adapted to other viral particles with known size relationships. The adjustment of AUC parameters (e.g., rotor speed, temperature, monitoring intervals) for different sample types is a routine optimization task for a PHOSITA operating AUC instrumentation.
3. Obvious Steps for Applying AUC:
   • Monitoring sedimentation, plotting C(s) vs S, and integrating peaks: These are standard operational procedures and data analysis techniques taught in the art of AUC. Schuck (2000) details the Lamm equation solutions and the SEDFIT algorithm for analyzing sedimentation velocity data to derive C(s) distributions. Cole et al. (2008) and Furst (1997) describe various optical detection methods (absorbance and interference) commonly used in AUC.
   • Identifying different species (empty, full, variant genomes): The ability of AUC to distinguish particles based on mass and shape means that different viral species (e.g., empty capsids lacking a genome versus full capsids containing a genome, or capsids with different genome sizes/aggregates) would inherently exhibit distinct sedimentation coefficients, leading to separable peaks in the C(s) distribution. Interpreting these peaks as different viral species (full, empty, variant) would be a straightforward and expected outcome for a PHOSITA applying AUC to viral preparations.
   • Assessing genome integrity via standard curves: The concept of establishing a correlation between a biophysical parameter (like sedimentation coefficient) and a molecular property (like genome size) using a standard curve is a routine analytical practice, especially once it is observed that different genome sizes yield different S-values (as shown in Figure 8 of US12031894B2 for AAV).
   • Monitoring purification and heterogeneity: The use of AUC as a quality control tool to monitor changes in particle populations (e.g., reduction of empty capsids or variant genomes, increase in full capsids) during purification steps is a logical extension of its analytical capabilities and a common application of analytical techniques in bioprocessing.

Therefore, the combination of Berkowitz & Philo (2007), which demonstrates the utility of AUC for adenovirus characterization, with the general knowledge in the field regarding AUC's versatility, the existence and properties of various recombinant viral vectors, and the ongoing need for their characterization, would have rendered the claimed methods obvious to a PHOSITA. The patent's own justification for extending AUC to AAV, lentivirus, and HSV further underscores this obviousness.

To provide a detailed analysis of US Patent 12031894, I will use the information available from the patent text and recent search results.

US Patent 12031894: Analytical Ultracentrifugation for Characterization of Recombinant Viral Particles

• Publication Number: US12031894B2
• Filing Date: 2023-11-20
• Publication Date (Issue Date): 2024-07-09
• Original Assignee: Genzyme Corp.

Continuation Applications, Divisional Applications, and Related Family Members:

The patent text explicitly states that US12031894 is a continuation of several earlier applications, forming a family:

• Continuation of: U.S. patent application Ser. No. 18/188,176, filed March 22, 2023.
• Which is a continuation of: U.S. patent application Ser. No. 16/547,144 (now U.S. Pat. No. 11,639,887), filed August 21, 2019.
• Which is a continuation of: U.S. patent application Ser. No. 15/544,498 (now U.S. Pat. No. 10,429,288), which adopts the international filing date of January 19, 2016.
• Which is a National Phase application under 35 U.S.C. § 371 of: International Application No. PCT/US2016/013947, filed January 19, 2016.
• Which claims priority to: U.S. Provisional Application No. 62/105,714, filed January 20, 2015.

This chain of applications indicates that US12031894 is part of a larger patent family, with its earliest priority date stemming from the U.S. Provisional Application No. 62/105,714 filed on January 20, 2015.

Patent Term Adjustments (PTA):

Patent Term Adjustment (PTA) extends the term of a U.S. patent to compensate for delays by the USPTO during prosecution. The general term for a U.S. utility patent is 20 years from its effective filing date, which for continuing applications is the earliest non-provisional filing date in the priority chain. Since US12031894 is a utility patent, it is eligible for PTA. However, the exact amount of PTA is determined by a complex calculation that accounts for specific delays in the prosecution of the application and any applicant-caused delays. Without direct access to the official USPTO patent record for US12031894 detailing the prosecution history and any PTA calculation, the specific amount of PTA cannot be definitively stated.

Patent Term Extensions (PTE):

Patent Term Extension (PTE) is available for certain patents covering products that undergo regulatory review, such as human drugs, biologics, and medical devices, to compensate for time lost during the approval process. The patent describes methods for characterizing recombinant viral particles, which are relevant to gene therapy products. Given that some claims relate to evaluating processes for the production of recombinant viral particles used in gene therapy, it is possible that this patent could be eligible for PTE if a product covered by the patent requires regulatory approval. For instance, recent news indicates that this patent is associated with gene therapy products like Elevidys®. However, an actual PTE can only be determined after regulatory approval has been granted and the appropriate application for extension has been filed with the USPTO and FDA. No information is currently available to confirm if a PTE has been applied for or granted for US12031894.

Projected Expiration Date:

The anticipated expiration date listed on the Google Patents page for US12031894B2 is 2036-01-19. This date is consistent with a 20-year term from the earliest non-provisional filing date of January 19, 2016 (from International Application No. PCT/US2016/013947, which is the national phase entry for the earliest priority claim, excluding the provisional application filing date) [cite: Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.) 2015-01-20]. The basic patent term for a U.S. utility patent is 20 years from the earliest non-provisional filing date. Therefore, 20 years from January 19, 2016, would be January 19, 2036. This projected expiration date would then be adjusted by any awarded PTA or PTE. Without the specific PTA value, the 2036-01-19 date is the most accurate available estimate.