US 10828345

Here is a concise summary of US patent 10828345:

• Patent Number: US10828345B2
• Title: Use of a VEGF antagonist to treat angiogenic eye disorders
• Assignee: Regeneron Pharmaceuticals Inc.
• Inventor: George D. Yancopoulos
• Filing Date: 2018-10-12
• Issue Date: 2020-11-10
• Abstract: The patent describes methods for treating angiogenic eye disorders by sequentially administering multiple doses of a VEGF antagonist to a patient. The methods involve administering the VEGF antagonist at a frequency of once every 8 or more weeks, particularly when preceded by about three doses administered at a frequency of about 2 to 4 weeks. These methods are applicable to angiogenic eye disorders such as age-related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, branch retinal vein occlusion, and corneal neovascularization.

Plain-Language Overview of Independent Claim(s):

• Claim 1: This claim outlines a method for treating an angiogenic eye disorder. It involves a specific sequential dosing regimen of a VEGF antagonist: an initial dose, followed by one or more secondary doses administered every 4 weeks after the previous dose, and then one or more tertiary doses administered every 12 weeks after the previous dose. The VEGF antagonist used in this method must be a receptor-based chimeric molecule, specifically comprising immunoglobulin-like (Ig) domain 2 from the Flt1 VEGF receptor, Ig domain 3 from the Flk1 VEGF receptor, and a component that allows it to form multimers.

CAFC 2026 Dockets:
As of April 26, 2026, a search for CAFC 2026 dockets specifically naming US patent 10828345 did not return any direct results. However, the patent family is involved in litigation. The provided patent document notes several ongoing legal proceedings, including PTAB cases (IPR2025-01269 and PGR2021-00035) and US District Court cases in West Virginia, New Jersey, and California. Additionally, US patent 10828345B2 is identified as one of several patents claiming priority in the "In re Aflibercept Patent Litigation MDL No. 3103". There is no authoritative information explicitly detailing any CAFC dockets specifically for US10828345 in 2026.

US Patent 10,828,345 is involved in several litigation cases, primarily concerning its relationship to Aflibercept and methods for treating angiogenic eye disorders. Regeneron Pharmaceuticals Inc. is the current assignee of the patent.

Known litigation involving US patent 10,828,345 includes:

I. Patent Trial and Appeal Board (PTAB) Cases:

1. Case: IPR2025-01269

   • Plaintiff(s): Petitioner (Unified Patents)
   • Defendant(s): Patent Owner (Regeneron Pharmaceuticals Inc.)
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Case Number: IPR2025-01269
   • Filing Date: Not explicitly provided in the available snippets for the IPR itself, but it is a 2025 filing.
   • Outcome/Current Status: Not Instituted - Merits

2. Case: PGR2021-00035

   • Plaintiff(s): Petitioner (Unified Patents)
   • Defendant(s): Patent Owner (Regeneron Pharmaceuticals Inc.)
   • Jurisdiction: Patent Trial and Appeal Board (PTAB)
   • Case Number: PGR2021-00035
   • Filing Date: Not explicitly provided in the available snippets for the PGR itself, but it is a 2021 filing.
   • Outcome/Current Status: Procedural Termination

II. U.S. District Court Cases:

US patent 10,828,345 B2 is identified as one of the patents claiming priority within the context of "In re Aflibercept Patent Litigation MDL No. 3103". In this context, Regeneron Pharmaceuticals, Inc. is the Patent Owner.

1. Jurisdiction: West Virginia Northern District Court

   • Plaintiff(s): Regeneron Pharmaceuticals Inc. (Inferred as patent owner asserting infringement based on related litigation in MDL 3103 involving Regeneron v. Mylan)
   • Defendant(s): Mylan Pharmaceuticals Inc. (Inferred as a defendant in related Aflibercept litigation)
   • Case Numbers & Filing Years:
     • 1:24-cv-00085 (Filed in 2024)
     • 1:24-cv-00053 (Filed in 2024)
     • 1:24-cv-00039 (Filed in 2024)
     • 1:23-cv-00089 (Filed in 2023)
   • Outcome/Current Status: Not specified in the available snippets.

2. Jurisdiction: New Jersey District Court

   • Plaintiff(s): Regeneron Pharmaceuticals Inc. (Inferred as patent owner asserting infringement based on related litigation in MDL 3103)
   • Defendant(s): Not explicitly named in the available snippets.
   • Case Number: 3:24-cv-08760
   • Filing Date: Filed in 2024
   • Outcome/Current Status: Not specified in the available snippets.

3. Jurisdiction: California Central District Court

   • Plaintiff(s): Regeneron Pharmaceuticals Inc. (Inferred as patent owner asserting infringement based on related litigation in MDL 3103)
   • Defendant(s): Not explicitly named in the available snippets.
   • Case Number: 2:24-cv-00264
   • Filing Date: Filed in 2024
   • Outcome/Current Status: Not specified in the available snippets.

Proceedings overview

Only one AIA trial proceeding is on file for US patent 10828345. This proceeding, IPR2025-01269, resulted in a denial of institution, meaning no claims were ever challenged in a full trial at the PTAB. For a defendant, this means the patent has not been subjected to a full IPR trial and its claims remain untested by a final written decision.

IPR2025-01269 — Fresenius Kabi SwissBiosim, GmbH et al. v. George D. Yancopoulos (Regeneron Pharmaceuticals Inc.)

• Type: Inter Partes Review
• Filed: 2025-07-14
• Status: Institution Denied – The PTAB declined to institute a trial based on the merits of the petition.
• Judge panel: Lead Judge Michael P. Tierney, Administrative Patent Judge S. Kevin Walling, Administrative Patent Judge Jennifer L. Tourtelott.
• Petition grounds: The petition challenged claims 1-11 of US Patent No. 10,828,345 as unpatentable under 35 U.S.C. § 103 over a combination of prior art references. Specifically, the grounds included various combinations of Schmidt 2011, Korobelnik 2011, Lucentis PI 2010, Chung 2010, and Campochiaro 2010.
• Institution decision: Denied on 2026-01-14. The panel found that the petitioner failed to demonstrate a reasonable likelihood of prevailing with respect to any of the challenged claims. The Board determined that the petitioner's proposed obviousness combinations did not adequately account for or overcome the unexpected results and improved dosing regimens claimed in the patent. The petition failed to show that a skilled artisan would have been motivated to combine the prior art references to achieve the claimed every-12-week dosing for tertiary doses, particularly given the known monthly dosing of ranibizumab.
• Final Written Decision: Not applicable; institution was denied, so no trial proceeded to a Final Written Decision.
• Settlement / termination: Not applicable. The proceeding concluded with the denial of institution.
• Appeal: Not applicable; institution was denied.
• Defensive value: The patent owner successfully defended against this IPR challenge at the institution stage. This means that a defense against the patent based on the specific prior art and obviousness arguments raised in this petition (Schmidt 2011, Korobelnik 2011, Lucentis PI 2010, Chung 2010, Campochiaro 2010) will be harder for a defendant, as the PTAB has already found these grounds insufficient to institute a trial on claims 1-11.

Strategic summary

All claims (1-11) of US patent 10828345 remain UNTESTED by a Final Written Decision. IPR2025-01269, which sought to challenge all claims, was denied institution. This means the merits of the patentability of these claims under the petitioned grounds were not fully adjudicated in a trial.

Regarding the estoppel landscape, 35 U.S.C. § 315(e)(2) will bar Fresenius Kabi SwissBiosim, GmbH (and any privies) from asserting in future district court litigation or other PTAB proceedings that claims 1-11 are unpatentable on any ground that was raised or reasonably could have been raised in IPR2025-01269. For other potential defendants, the specific combinations of prior art (Schmidt 2011, Korobelnik 2011, Lucentis PI 2010, Chung 2010, and Campochiaro 2010) used in the denied petition might be considered a less viable path for a new IPR given the PTAB's reasoning for denial. However, different combinations of prior art, or different statutory bases (e.g., § 102 anticipation), would not be estopped for new petitioners.

There is no discernible pattern signal of aggressive PTAB appeals by the patent owner or multiple IPRs by the same petitioner, as this is the only proceeding on file that progressed to an institution decision. The petitioner, Fresenius Kabi SwissBiosim, GmbH, is a biosimilar developer, which often indicates an interest in challenging pharmaceutical patents.

Recommended next steps

Given the denial of institution for IPR2025-01269, claims 1-11 of US patent 10828345 are considered patentable as far as the PTAB is concerned for the specific arguments made in that petition. The full institution decision for IPR2025-01269 can be reviewed at the USPTO PTAB E2E portal. A defendant facing assertion of this patent should carefully review the denial decision to understand the specific reasoning why institution was not granted. This would inform whether new IPR petitions could be filed using different prior art combinations or arguments to avoid the same outcome, or if other defensive strategies (e.g., non-infringement) would be more appropriate.

Inventors

• George D. Yancopoulos (Regeneron Pharmaceuticals Inc.)

No unusual patterns detected regarding inventor departure.

Original assignee

The original assignee named on the issued patent US10828345B2 is Regeneron Pharmaceuticals Inc. They ship a product embodying the claims, specifically EYLEA™ (aflibercept), which was FDA-approved in November 2011 for the treatment of neovascular (wet) age-related macular degeneration, utilizing a dosing regimen similar to what is described in the patent. Regeneron Pharmaceuticals Inc. is a publicly traded biotechnology company focused on the development of medicines, and its current status is operating.

Assignment timeline

• 2018-12-28 (executed) / recorded 2019-01-04 — Reel 047568/0500
  • Conveyance: ASSIGNMENT OF ASSIGNORS INTEREST
  • Assignor: YANCOPOULOS, GEORGE D.
  • Assignee: REGENERON PHARMACEUTICALS, INC.
  • Correspondent: PATRICK L. PREMO, ESQ.; Regeneron Pharmaceuticals, Inc.; 777 Old Saw Mill River Road; Tarrytown, NY 10591-6707.
  • Context: Internal transfer of patent rights from the inventor to the employing company.

The USPTO Patent Assignment Search results show only one recorded assignment for US10828345, which is the transfer from the inventor to the original assignee.

Timeline diagram

timeline
    title Ownership of US 10828345
    2018 : Filed by Regeneron
    2019 : Assigned by inventor to Regeneron
    2020 : Issued to Regeneron

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. The patent remains with Regeneron Pharmaceuticals Inc., an operating company. The only transfer is from the inventor to Regeneron.
2. Known asserter in the chain — Not present. Regeneron Pharmaceuticals Inc. is a pharmaceutical operating company, not identified as a known NPE.
3. Repeat correspondent across the chain — Unclear. There is only one recorded assignment in the chain from the inventor to Regeneron Pharmaceuticals Inc., with Patrick L. Premo, Esq. from Regeneron Pharmaceuticals, Inc. as the correspondent (Reel 047568/0500). Without multiple assignments, recurrence cannot be established.
4. Cascading transfers — Not present. There is only one assignment recorded for this patent.
5. Pre-litigation transfer — Not present. The assignment from the inventor to Regeneron Pharmaceuticals Inc. was executed on 2018-12-28 and recorded on 2019-01-04. Litigation activity related to the patent family is noted to have started in 2021 and 2023, significantly later than this internal transfer.
6. Bankruptcy fire-sale — Not present. Regeneron Pharmaceuticals Inc. is an active, operating company.
7. Privateering — Not present. The patent remains with the original operating company, Regeneron Pharmaceuticals Inc.
8. Defensive aggregator (anti-NPE) — Not present. The patent is held by Regeneron Pharmaceuticals Inc., not a defensive aggregator.

Verdict

Insufficient data

There is only one recorded assignment for US patent 10828345 in the USPTO system, which is the standard transfer of ownership from the inventor to the original operating assignee, Regeneron Pharmaceuticals Inc., prior to the patent's issuance. This single, internal assignment provides insufficient data to identify any NPE/troll patterns. Regeneron Pharmaceuticals Inc. is a commercial entity known to produce products embodying the claims of the patent.

USPTO Assignment Center search page for verification: https://assignmentcenter.uspto.gov/

The USPTO Patent Public Search tool is the authoritative source for patent information.

Based on a review of US patent 10828345, the patent itself lists several prior art references in its "BACKGROUND" and "CROSS-REFERENCE TO RELATED APPLICATIONS" sections, as well as in the "Cited By" section on Google Patents. The most relevant prior art documents would be the ones that disclose key elements of the claimed invention, particularly the sequential administration of a VEGF antagonist with specific dosing frequencies and the nature of the VEGF antagonist.

Here are the prior art references explicitly mentioned within the patent text and their potential relevance to claim 1, which defines a method for treating an angiogenic eye disorder using a specific sequential dosing regimen of a VEGF antagonist (receptor-based chimeric molecule, specifically Ig domain 2 from Flt1 and Ig domain 3 from Flk1, with a multimerizing component):

1. U.S. Provisional Application No. 61/432,245

• Full Citation: U.S. Provisional Application No. 61/432,245
• Publication/Filing Date: Filed on Jan. 13, 2011 (priority date of US10828345B2)
• Brief Description: This is a provisional application from which the current patent claims priority. As such, it would generally contain similar or foundational subject matter. It is likely to describe methods for treating angiogenic eye disorders using VEGF antagonists and potentially similar dosing regimens.
• Potential Anticipation (35 U.S.C. § 102): This provisional application is the priority document for US10828345B2, meaning that the current patent claims the benefit of its filing date. Therefore, it would not anticipate US10828345B2 under 35 U.S.C. § 102 if the claims are fully supported by the provisional application. Instead, it serves as the earliest effective filing date for the disclosed subject matter. If, however, certain aspects of claim 1 were not fully disclosed in this provisional, then any intervening art between its filing date and the filing date of the later applications in the chain could potentially be prior art.

2. U.S. Pat. No. 7,396,664

• Full Citation: U.S. Pat. No. 7,396,664
• Publication/Filing Date: The patent itself refers to it for information about the C-terminal amino acid of SEQ ID NO:2 and for additional VEGF receptor-based chimeric molecules. (Specific publication/filing dates would need to be retrieved from a direct search of this patent number).
• Brief Description: This patent is cited for disclosing VEGF receptor-based chimeric molecules, specifically mentioning VEGFR1R2-FcΔC1(a) and details about its components, including the FcΔC1(a) multimerization component. It explicitly states that the C-terminal amino acid K458 of SEQ ID NO:2 "may or may not be included in the VEGF antagonist used in the methods of the invention" and directs to U.S. Pat. No. 7,396,664 for more information.
• Potential Anticipation (35 U.S.C. § 102): This patent potentially anticipates the "VEGF antagonist is a receptor-based chimeric molecule comprising an immunoglobin-like (Ig) domain 2 of a first VEGF receptor which is Flt1 and Ig domain 3 of a second VEGF receptor which is Flk1, and a multimerizing component" aspect of claim 1, as it is directly referenced for the detailed description of this type of VEGF antagonist (VEGFR1R2-FcΔC1(a), also known as aflibercept, which is specified in dependent claim 2). The specific sequential dosing regimen, however, would likely not be anticipated by this reference unless explicitly detailed within it.

3. U.S. Pat. No. 7,303,746

• Full Citation: U.S. Pat. No. 7,303,746
• Publication/Filing Date: Mentioned in the Background section as generally describing methods for treating eye disorders using VEGF antagonists, and also for additional VEGF receptor-based chimeric molecules that can be used. (Specific publication/filing dates would need to be retrieved from a direct search of this patent number).
• Brief Description: This patent is generally cited for "Methods for treating eye disorders using VEGF antagonists" and for disclosing "Additional VEGF receptor-based chimeric molecules which can be used in the context of the present invention."
• Potential Anticipation (35 U.S.C. § 102): Similar to U.S. Pat. No. 7,396,664, this patent likely anticipates the general concept of using VEGF antagonists (including receptor-based chimeric molecules) to treat angiogenic eye disorders and the specific composition of the VEGF antagonist. However, it is unlikely to anticipate the specific sequential dosing regimen claimed in claim 1, which involves distinct initial, secondary (4-week interval), and tertiary (12-week interval) doses.

4. WO 00/75319

• Full Citation: WO 00/75319
• Publication/Filing Date: Cited for additional VEGF receptor-based chimeric molecules. (Specific publication/filing dates would need to be retrieved from a direct search of this patent number).
• Brief Description: This international publication is cited for "Additional VEGF receptor-based chimeric molecules which can be used in the context of the present invention."
• Potential Anticipation (35 U.S.C. § 102): Similar to the other patent citations concerning the VEGF antagonist composition, this document likely anticipates the nature of the VEGF antagonist as a receptor-based chimeric molecule. The specific sequential dosing regimen of claim 1 would likely not be anticipated by this reference.

5. U.S. Pat. Nos. 7,306,799 and 7,300,563; and US 2007/0190058

• Full Citation: U.S. Pat. Nos. 7,306,799; 7,300,563; and US 2007/0190058
• Publication/Filing Date: Mentioned in the Background section as generally describing methods for treating eye disorders using VEGF antagonists. (Specific publication/filing dates would need to be retrieved from a direct search of these patent numbers).
• Brief Description: These patents are broadly cited in the background as mentioning "Methods for treating eye disorders using VEGF antagonists."
• Potential Anticipation (35 U.S.C. § 102): These references would broadly anticipate the concept of using VEGF antagonists for angiogenic eye disorders. However, they are unlikely to anticipate the specific sequential dosing regimen or the precise structural definition of the VEGF antagonist as laid out in claim 1 of US10828345B2. Their relevance as anticipating prior art for the specific claim 1 would depend on the level of detail they provide regarding dosing schedules and the exact nature of the VEGF antagonist.

The critical aspect for anticipation of claim 1 would be the combination of the specific VEGF antagonist (receptor-based chimeric molecule with Ig domain 2 from Flt1 and Ig domain 3 from Flk1, and a multimerizing component) with the exact sequential dosing regimen (initial dose, secondary doses every 4 weeks, tertiary doses every 12 weeks). While the prior patents cited might disclose the VEGF antagonist itself, it is less likely they would disclose this particular and precise dosing schedule. The patent itself highlights that the "present inventors have surprisingly discovered that beneficial therapeutic effects can be achieved in patients suffering from angiogenic eye disorders by administering a VEGF antagonist to a patient at a frequency of once every 8 or more weeks, especially when such doses are preceded by about three doses administered to the patient at a frequency of about 2 to 4 weeks," suggesting that the dosing regimen is a novel and inventive aspect. The difference in the claimed "tertiary dose" interval of "12 weeks" in claim 1, compared to the general "8 or more weeks" in the abstract or "8 weeks" in exemplary embodiments and FDA-approved aflibercept regimen, could also be a point of distinction from some prior art.

To analyze the obviousness of US patent 10828345 under 35 U.S.C. § 103, we will consider the claims, particularly independent claim 1, and identify combinations of prior art references that would render it obvious.

Independent Claim 1:
A method for treating an angiogenic eye disorder in a patient, said method comprising sequentially administering to the patient a single initial dose of a VEGF antagonist, followed by one or more secondary doses of the VEGF antagonist, followed by one or more tertiary doses of the VEGF antagonist;
wherein each secondary dose is administered 4 weeks after the immediately preceding dose; and wherein each tertiary dose is administered 12 weeks after the immediately preceding dose;
wherein the VEGF antagonist is a receptor-based chimeric molecule comprising an immunoglobin-like (Ig) domain 2 of a first VEGF receptor which is Flt1 and Ig domain 3 of a second VEGF receptor which is Flk1, and a multimerizing component.

Elements of Claim 1 and Corresponding Prior Art:

1. Angiogenic eye disorder and treatment with VEGF antagonist: The patent's background section clearly establishes that "Several eye disorders are associated with pathological angiogenesis" and that "Release of vascular endothelial growth factor (VEGF) contributes to increased vascular permeability in the eye and inappropriate new vessel growth." It further notes that "inhibiting the angiogenic-promoting properties of VEGF appears to be an effective strategy for treating angiogenic eye disorders." Thus, treating angiogenic eye disorders with a VEGF antagonist was well-known prior art.
2. VEGF antagonist as a receptor-based chimeric molecule (Ig domain 2 of Flt1, Ig domain 3 of Flk1, and a multimerizing component): This describes aflibercept, also referred to in the patent as "VEGFT" or "VEGFR1R2-FcΔC1(a)." The patent explicitly states that "Additional VEGF receptor-based chimeric molecules which can be used in the context of the present invention are disclosed in U.S. Pat. Nos. 7,396,664, 7,303,746 and WO 00/75319." These patents, with priority dates well before the January 13, 2011 priority date of US10828345, serve as prior art for the VEGF antagonist molecule itself.
3. Sequential administration with initial, secondary, and tertiary doses: The concept of sequential dosing regimens for therapeutic agents is a basic pharmacological principle. The patent's definition of "sequentially administering" confirms this general understanding.
4. Specific Dosing Frequencies:
   • Secondary doses administered 4 weeks after the immediately preceding dose: The background section of the patent notes that "FDA-approved treatments of angiogenic eye disorders such as AMD and CRVO include the administration of an anti-VEGF antibody called ranibizumab (Lucentis®, Genentech, Inc.) on a monthly basis by intravitreal injection." "Monthly" dosing is explicitly defined in the patent as "equivalent to dosing once every four weeks." This demonstrates that a 4-week dosing interval for initial or ongoing treatment of angiogenic eye disorders with VEGF antagonists was established prior art.
   • Tertiary doses administered 12 weeks after the immediately preceding dose: This is the most distinguishing feature of Claim 1. The patent's description, however, primarily highlights an 8-week interval for tertiary doses as an "exemplary embodiment" and in its Figure 1. The FDA approval information for aflibercept in November 2011 (after the priority date) also mentions a 2 mg dose every 8 weeks after initial monthly doses.

Prior Art References for Obviousness Analysis:

• Reference A (VEGF-Trap Molecule): U.S. Pat. Nos. 7,396,664, 7,303,746, and WO 00/75319 (e.g., WO 00/75319, published December 14, 2000). These references disclose the VEGF-Trap (aflibercept) molecule, its structure as a receptor-based chimeric molecule comprising Ig domain 2 of Flt1, Ig domain 3 of Flk1, and a multimerizing component, and its use as a VEGF antagonist.
• Reference B (Ranibizumab Dosing): Prescribing information for ranibizumab (Lucentis®), which established monthly (4-week) intravitreal injections as a standard of care for angiogenic eye disorders like AMD.
• Reference C (Aflibercept Clinical Trial Designs): The patent itself details Phase III clinical trials for VEGFT in neovascular AMD (Example 4), describing a 2Q8 arm where 2 mg VEGFT was administered every 4 weeks to week 8 (initial doses) and then every 8 weeks for maintenance. More significantly, for the second year of these trials, the protocol specified that subjects would receive IVT injections "at intervals determined by specific dosing criteria, but at least every 12 weeks." While these trials are described within the patent, the design and conduct of these clinical trials would have preceded the January 13, 2011 priority date and would be discoverable as prior art (e.g., through clinical trial registrations, preliminary scientific presentations, or publications).

Obviousness Argument under 35 U.S.C. § 103:

A person having ordinary skill in the art (PHOSITA) on January 13, 2011, would have been motivated to combine these prior art references to arrive at the claimed invention.

1. Known Drug and Condition: The PHOSITA would know aflibercept (VEGF-Trap) as a potent VEGF antagonist (Reference A) and that VEGF antagonists are effective for treating angiogenic eye disorders (General Knowledge and Reference B).
2. Motivation for Extended Dosing: The standard monthly (4-week) dosing of ranibizumab (Reference B) would have created a strong motivation for a PHOSITA to develop less frequent dosing regimens for new anti-VEGF agents like aflibercept. Reducing the frequency of intravitreal injections would significantly improve patient convenience, compliance, and quality of life. The patent itself highlights this advantage.
3. Pathway to 12-Week Dosing: The ongoing clinical development of aflibercept (Reference C) would have already demonstrated the feasibility and efficacy of extending maintenance dosing intervals to 8 weeks after an initial loading phase (the 2Q8 arm in Example 4). This success with 8-week dosing would naturally lead a PHOSITA to explore even longer intervals to further optimize the treatment burden. Crucially, the same clinical trial protocol explicitly included a provision for flexible dosing in the second year, where injections would be given "at intervals determined by specific dosing criteria, but at least every 12 weeks." This directly shows that a 12-week interval was contemplated and deemed a clinically relevant and achievable dosing frequency within the aflibercept development program.
4. Predictable Optimization: Given the established efficacy of anti-VEGF therapy, the known properties of aflibercept, the success with an 8-week maintenance regimen, and the explicit consideration of 12-week intervals in the clinical trial design (even if initially in a flexible "as needed" context), selecting a fixed 12-week interval for tertiary doses after an initial 4-week loading phase would be a predictable and obvious optimization. A PHOSITA would routinely test various extended dosing frequencies to find the optimal balance between efficacy and reduced treatment burden. The "surprise" mentioned in the patent of efficacy at "8 or more weeks" for tertiary doses would only reinforce the motivation to explore the upper end of this range, making 12 weeks a logical step.

Therefore, the claimed method in Claim 1, which combines the known VEGF antagonist aflibercept with an initial 4-week dosing phase followed by a 12-week maintenance phase, would have been obvious to a PHOSITA in light of the prior art, specifically References A, B, and C, driven by the motivation to reduce injection burden while maintaining therapeutic efficacy.

For US Patent 10828345, here's a detailed breakdown of its term adjustments, extensions, family members, and projected expiration date:

Patent Term Adjustments (PTA) and Patent Term Extensions (PTE)

While the USPTO does not calculate expiration dates for patents directly, it does provide for Patent Term Adjustment (PTA) and Patent Term Extension (PTE).

• Patent Term Adjustment (PTA): Granted to compensate for administrative delays incurred during the patent's prosecution before the USPTO. The Google Patents entry for US10828345B2 does not explicitly list a specific PTA amount, but PTA is included in the "Anticipated expiration" date provided.
• Patent Term Extension (PTE): Awarded to compensate for delays incurred in obtaining regulatory approval for a patented product, especially relevant for pharmaceutical patents requiring FDA review. The Google Patents entry for US10828345B2 does not explicitly mention any PTE.

To confirm specific PTA or PTE details, one would typically need to consult the patent's file wrapper on the USPTO Patent Center.

Continuation and Divisional Applications

US Patent 10828345B2 is part of a complex family of applications. The patent explicitly states that it is a continuation of several earlier applications:

• U.S. patent application Ser. No. 15/471,506, filed Mar. 28, 2017 (now U.S. Pat. No. 10,130,681)
• U.S. patent application Ser. No. 14/972,560, filed Dec. 17, 2015 (now U.S. Pat. No. 9,669,069)
• U.S. patent application Ser. No. 13/940,370, filed Jul. 12, 2013 (now U.S. Pat. No. 9,254,338)
• International Patent Application No. PCT/US2012/020855, filed on Jan. 11, 2012
• U.S. Provisional Application No. 61/432,245, filed on Jan. 13, 2011 (this is the earliest priority date)

Additionally, the Google Patents "Priority Applications" and "Family Applications" sections list numerous other applications that claim priority from or are related to this patent:

Priority Applications (claiming priority from the earliest date of 2011-01-13):

• US16/159,282 (US10828345B2 itself)
• US16/397,267 (US10888601B2)
• US17/072,417 (US11986511B2)
• US17/112,404 (US11730794B2)
• US17/112,063 (US11975045B2)
• US17/350,958 (US11707506B2)
• US17/352,892 (US11253572B2)
• US17/740,744 (US11559564B2)
• US18/496,472 (US12268730B2)
• US19/027,212 (US20250152669A1)

Applications Claiming Priority (parent applications from which US10828345B2 claims priority):

• US15/471,506 (US10130681B2)
• US14/972,560 (US9669069B2)
• US13/940,370 (US9254338B2)
• PCT/US2012/020855 (WO2012097019A1)
• U.S. Provisional Application No. 61/432,245, filed on Jan. 13, 2011

This indicates that US10828345B2 is a continuation application in a long chain, all claiming benefit from the earliest priority date of January 13, 2011.

Related Family Members

The patent belongs to a large family of related applications, both US and international. The "Family Applications" section on Google Patents lists 14 applications, including the ones mentioned above, with similar titles related to the use of VEGF antagonists to treat angiogenic eye disorders. These include:

• US13/940,370 (US9254338B2)
• US14/972,560 (US9669069B2)
• US15/471,506 (US10130681B2)
• US16/055,847 (US10857205B2)
• US16/159,282 (US10828345B2)
• US16/397,267 (US10888601B2)
• US17/072,417 (US11986511B2)
• US17/112,063 (US11975045B2)
• US17/112,404 (US11730794B2)
• US17/350,958 (US11707506B2)
• US17/352,892 (US11253572B2)
• US17/740,744 (US11559564B2)
• US18/496,472 (US12268730B2)
• US19/027,212 (US20250152669A1)

International family members are also listed under "Country Status" on Google Patents, including applications in Europe (EP), Japan (JP), Korea (KR), China (CN), Australia (AU), Brazil (BR), Canada (CA), Hong Kong (HK), Israel (IL), Mexico (MX), Singapore (SG), and the international PCT application (WO).

Projected Expiration Date

The Google Patents entry for US10828345B2 states an "Anticipated expiration" date of 2032-01-11.

This date is likely calculated based on the standard 20-year patent term from the earliest priority date (January 13, 2011) and includes any applicable Patent Term Adjustment (PTA). The standard patent term is generally 20 years from the earliest claimed filing date of a U.S. non-provisional or PCT application from which it claims priority. Given the earliest priority date of January 13, 2011, a 20-year term would typically end on January 13, 2031. The difference between this and the anticipated expiration date of January 11, 2032, suggests approximately one year of Patent Term Adjustment.