US 7435745

I'll search for authoritative information on this specific patent number.

I have strong bibliographic data. Now let me retrieve the actual claim text.

Let me try to retrieve the specific claim language for this patent.

US Patent 7,435,745 — Analyst Summary

Source note: The authoritative document text you supplied is truncated before the claims section (it ends mid‑Example III). I therefore report claim information with explicit caveats and flag exactly where I could not obtain authoritative text. Bibliographic data below is corroborated by the issued patent front page (PDF via Google Patents image store), Justia Patents, uspto.report, and DrugPatentWatch.

1. Bibliographic record

A related continuation, US 8,039,488 B2 (application 12/249,847), belongs to the same family.

2. Abstract (verbatim)

"The present invention comprises a group of compounds that effectively inhibit angiogenesis. More specifically, thalidomide and various related compounds such as thalidomide precursors, analogs, metabolites and hydrolysis products have been shown to inhibit angiogenesis and to treat disease states resulting from angiogenesis. Additionally, antiinflammatory drugs, such as steroids and NSAIDs can inhibit angiogenesis dependent diseases either alone or in combination with thalidomide and related compounds. Importantly, these compounds can be administered orally."

3. Disclosure in brief

The specification teaches:

• Core compounds: thalidomide and teratogenic/dysmelia‑causing analogs, precursors, hydrolysis products and metabolites — expressly EM‑12, EM‑138, N‑phthaloyl‑DL‑glutamic acid (PGA), N‑phthaloyl‑DL‑glutamine anhydride (col. describing FIGS. 1–5 genera).
• Epoxide embodiments: epoxides of thalidomide, EM‑12 and EM‑138, their hydrolysis (hydroxyl/dihydroxyl) products, and co‑administration with epoxide hydrolase inhibitors (valpromide, valproic acid) to potentiate epoxide‑containing agents (AGM 1470, Eponimycin, Scolecobasidium arenarium metabolites f/2015, fr/111142, fr/18487).
• Anti‑inflammatory co‑therapy: steroids (hydrocortisone, dexamethasone, betamethasone especially preferred) and NSAIDs (indomethacin and sulindac especially preferred; also sulindac sulfone/sulfide, NS‑398, thromboxane inhibitors, etc.), used alone or in combination with the angiogenesis inhibitors.
• Working examples: chick CAM assay (Example I), rabbit cornea bFGF pellet assay (Example II), thalidomide/EM‑12 dose–response (Example III), mouse cornea bFGF/VEGF assays, a Crohn's disease human case, and rabbit V2‑carcinoma tumor growth. Key data: thalidomide + sulindac gave 65% (bFGF) / 74% (VEGF) inhibition versus 42–52% for either alone; V2‑carcinoma T/C = 0.32 and ~75% tumor‑growth inhibition for the combination.
• Indications: ocular neovascular disease (macular degeneration, diabetic retinopathy, neovascular glaucoma, retrolental fibroplasia, corneal and retinal/choroidal neovascularization), rheumatoid/osteoarthritis, chronic inflammatory disease (Crohn's, ulcerative colitis, psoriasis, sarcoidosis), hemangioma, Osler‑Weber‑Rendu disease, solid and blood‑borne tumors/metastasis, and (in the description) AIDS.
• Dosing: oral, ~0.1–300 mg/kg/day; preferred ~0.5–50; most preferred ~1–10 mg/kg/day.

4. Claims — status and caveats

I could not retrieve the authoritative, verbatim claim set of US 7,435,745 from the sources returned. The Google Patents text you supplied stops before the claims, and my searches surfaced the claim text of sibling/related patents (e.g., US 5,712,291 and US 8,143,283) rather than the '745 claims themselves. I will not reconstruct claim language I cannot verify.

What can be stated with reasonable confidence:

• Claim type. DrugPatentWatch classifies the '745 claims as "Use" claims (method‑of‑use), consistent with the specification's orientation toward methods of treating angiogenesis‑mediated disease. The front‑page classification (A61K 31/445, 514/323) is likewise a method/medicinal‑preparation class rather than a compound class.
• Family lineage caution. This patent sits in the D'Amato thalidomide/angiogenesis family that includes US 5,593,990, US 5,629,327, US 5,712,291, US 6,071,948 and US 8,039,488. Those family members claim, e.g., "A method of treating undesired angiogenesis in a human or animal comprising … an effective amount of an angiogenesis‑inhibiting compound selected from the group consisting of 3‑aminothalidomide and 3‑hydroxythalidomide …" (US 5,712,291, claim 1). The '745 specification is the same disclosure (priority Nov. 5, 1996), but the '745 claims themselves may differ in scope — likely directed to thalidomide/related compounds and possibly to anti‑inflammatory (steroid/NSAID) combinations — and I cannot confirm their exact wording.
• No 2026 CAFC docket found. I found no Court of Appeals for the Federal Circuit activity in 2026 for this patent. Given that the patent is recorded as expired (anticipated expiration Nov. 3, 2017) and its known litigation is in the District of New Jersey (2007 and 2015 case numbers), a 2026 CAFC docket entry would be unusual; I found none in the sources retrieved and cannot rule out a docket not indexed by the search tools used.

Bottom line on claims: Treat any specific independent‑claim wording for US 7,435,745 as unverified until checked directly against the USPTO PatentCenter/Patent Public Search full‑text or the granted‑patent PDF (columns after the examples). I recommend pulling the "What is claimed is" section from the USPTO full‑text or the Google Patents PDF page range following the specification, and I flag this as an explicit uncertainty rather than asserting claim language I have not seen.

I'll research litigation involving US patent 7435745. Let me search several sources.

Let me dig deeper into the specific cases indicated on the patent's litigation links.

Let me search for the specific Celgene/CMCC v. Lannett case that asserted the '745 patent.

Litigation Involving U.S. Patent No. 7,435,745

Patent identity (confirmed from the authoritative patent text and litigation records): U.S. Patent No. 7,435,745, "Methods and Compositions for Inhibition of Angiogenesis," inventor Robert J. D'Amato, granted October 14, 2008, from Application No. 11/411,230 (filed April 26, 2006), priority date November 5, 1996. Original assignee of record was Celgene Corp.; a certificate of correction dated April 7, 2009 corrected the assignee to CMCC (The Children's Medical Center Corporation), and the patent is exclusively licensed to Celgene. Current Google Patents legal status: Expired – Fee Related (anticipated expiration 2017-11-03).

The Google Patents page for this patent lists exactly two litigation links, both in the District of New Jersey: case 2:07-cv-00286 and case 2:15-cv-00697. Here is what those cases are, plus directly related matters.

1. Celgene Corp. v. Lannett Holdings, Inc. — D.N.J. No. 2:15-cv-00697

• Plaintiff(s): Celgene Corporation (pleading jointly with CMCC as to the '745 patent, which is licensed from CMCC — the complaint is captioned with "Plaintiffs")
• Defendant(s): Lannett Holdings, Inc. (Lannett)
• Jurisdiction: U.S. District Court for the District of New Jersey
• Case No.: 2:15-cv-00697 (docket also shown as 2:15-cv-00697-SDW-SCM; later 2:15-cv-00697-MCA-MAH as the assigned judges changed). Presiding judge cited as Judge Wigenton.
• Filing date: January 30, 2015 (pleaded as "early 2015" / "January 23, 2015" in some third-party complaints)
• Nature: Hatch-Waxman ANDA litigation. Celgene sued Lannett after Lannett filed ANDA No. 206-601 for generic thalidomide capsules (50, 100, 150, 200 mg) with a Paragraph IV certification. Celgene asserted fifteen (15) patents, expressly including the '745 patent. Lannett counterclaimed that the patents were invalid, unenforceable, and/or not infringed, and added antitrust/sham-litigation counterclaims.
• Outcome / status: On October 10, 2017, the parties stipulated to a settlement in which Lannett changed its Paragraph IV certification on the '745 patent to a Paragraph III certification and agreed not to seek FDA approval of its ANDA before the '745 patent's expiration; Celgene dismissed its infringement claims. On October 30, 2017, the parties announced a settlement and license agreement (terms confidential) permitting Lannett to manufacture and market generic thalidomide as of August 1, 2019.

This is the primary case in which the '745 patent was affirmatively asserted.

2. Celgene Corp. v. Barr Laboratories, Inc. — D.N.J. No. 2:07-cv-00286

• Plaintiff(s): Celgene Corporation
• Defendant(s): Barr Laboratories, Inc. and Barr Pharmaceuticals, Inc.
• Jurisdiction: U.S. District Court for the District of New Jersey
• Case No.: 2:07-cv-00286 (also shown as 2:07-cv-00286-SDW-MCA)
• Filing date: January 18, 2007
• Nature: Hatch-Waxman litigation over Barr's thalidomide ANDA (filed September 22, 2006; accepted for filing December 4, 2006) for generic Thalomid®. Barr counterclaimed for patent invalidity and antitrust violations (monopolization, conspiracy to monopolize, sham litigation).
• Outcome / status: In May 2010 Barr withdrew its thalidomide ANDA; the court granted the parties' stipulated dismissal of all claims (stipulated dismissal dated/filed May 21, 2010), including dismissal with prejudice of Barr's patent and antitrust counterclaims.

Caveat (strict-identifier note): The '745 patent did not issue until October 14, 2008 — nearly two years after the Barr complaint was filed on January 18, 2007. The '745 patent therefore could not have appeared in the original Barr complaint and could only have been brought in by later amendment. The Google Patents page associates case 2:07-cv-00286 with this patent (and several secondary complaints state that "In 2008, Celgene filed a patent infringement lawsuit against Barr"), but I could not confirm from the sources retrieved that the '745 patent was directly asserted against Barr, as opposed to being family-associated. Treat the Barr case as substantially certain to be related but not confirmed as a direct '745 assertion.

3. Related / ancillary matters (not direct '745 infringement suits)

• The Children's Medical Center Corp. v. Celgene Corp., No. 13-11573 (D. Mass.) — dispute over the license/royalty arrangement covering CMCC's thalidomide-analog patent portfolio (of which the '745 patent is the '745 member, exclusively licensed to Celgene). This is a license/contract dispute, not an infringement action on the '745 patent, but it is the source of the ownership/license posture of the '745 patent. (Post-trial decisions cited at 2016 WL 3561603 and 2016 WL 5746358.)
• In re Thalomid and Revlimid Antitrust Litigation, D.N.J. No. 2:14-cv-06997 (and related payor/class complaints, e.g., 2:17-cv-04319, 2:20-cv-18531, 2:21-cv-00090, 2:21-cv-20451) — these are antitrust actions against Celgene in which the '745 patent is referenced as an allegedly "unenforceable and invalid" patent that Celgene "leveraged" in the Lannett litigation, but the '745 patent itself was not asserted in these suits.
• Earlier Celgene/EntreMed v. CMCC dispute (resolved by a 2002 exclusive license agreement) — background to the '745 patent's ownership; not a '745 assertion.

Summary

No other litigation specifically asserting U.S. Patent No. 7,435,745 was identified. I did not locate any Federal Circuit appeal, ITC action, or IPR/PGR directed to the '745 patent itself (IPR2015-01103, sometimes surfaced in searches, concerns U.S. Pat. No. 6,315,720, not the '745 patent). If you need PACER-level verification of the dockets, the two New Jersey docket numbers above are the authoritative citations to pull.

I'll verify the structured "no proceedings on file" result against public sources before writing up.

Let me run additional targeted checks for any proceeding naming this patent or its family, and for the litigation context.

Let me do two final confirmatory searches — one directly on the PTAB docket, one on the patent's litigation docket for any IPR cross-reference.

PTAB / AIA Trial Analysis — US Patent 7,435,745

Source hierarchy used: The canonical "PTAB proceedings on file" block (USPTO Open Data Portal) states no AIA trial proceedings. I attempted to corroborate and extend this with web searches on 2026-10-01. Search was truncated by a step limit before the last two confirmatory queries completed; the queries that did run returned no IPR/PGR/CBM naming US 7,435,745. Findings and residual uncertainty are flagged below.

Proceedings overview

Total AIA trial proceedings on US 7,435,745: 0 — zero active, zero claims invalidated, zero claims sustained, zero settled, zero institution denials. The USPTO ODP record returns no IPR, PGR, or CBM for this patent, and my searches independently surfaced nothing naming the '745 patent as the patent-at-issue.

Bottom-line defensive posture: There is no PTAB record to lean on and no estoppel to exploit — but also no dead claims. No AIA tribunal has ever construed a '745 claim or invalidated one. A defendant today therefore cannot say "claims 1–5 are canceled"; instead the operative facts are that (a) the patent is recorded Expired – Fee Related, with anticipated expiration 2017-11-03, and (b) its validity has never been tested in an AIA trial. For an assertion today, that shifts the fight to past damages and laches/§ 286 damages-window limits, not prospective injunctive relief, and any validity attack would have to be litigated in district court or via ex parte reexamination (a third-party ex parte reexam is still possible; IPR against an expired patent is disfavored/moot as to amendment but not categorically barred).

⚠️ Disambiguation warning. "745" shorthand collides badly. Many of my hits for "the '745 patent" refer to US 10,687,745 (Masimo/Al-Ali) — the pulse-oximetry patent in Apple v. Masimo (IPR2022-01292, IPR2025-01291, etc.). Those proceedings have nothing to do with US 7,435,745. Do not import them.

No proceedings to enumerate

The requested per-proceeding format cannot be populated because the canonical list is empty. I will not synthesize proceeding numbers, panels, or FWDs that do not exist. Instead, below is the closest family-level PTAB activity, clearly labeled as NOT proceedings on the '745 patent — useful context, not a substitute.

Context only — sibling-patent AIA activity (does NOT involve US 7,435,745)

IPR2015-01169 — Coalition for Affordable Drugs VI LLC v. Celgene Corporation

• Patent-at-issue: US 5,635,517 (the lenalidomide/pomalidomide TNF-α "compound" patent) — not the '745 patent.
• Type: Inter Partes Review
• Filed: 2015-05-07
• Status: Institution denied — PTAB declined to institute on 2015-11-16.
• Grounds (as reported in the Revlimid/Thalomid purchaser antitrust complaints): art included Piper (1981), Kaplan (1995), Agrawal (1981), WO 94/20085 (D'Amato) and Keith (1992); the panel was "not persuaded that an ordinary artisan would have had sufficient reason to prepare any of the four compounds recited in claim 10."
• Defensive value: Nicely illustrates the family's litigation history and the Coalition for Affordable Drugs (Hayman Capital-funded) petitioning pattern — but it created no estoppel and no claim-level outcome for the '745 patent.

Other family challenges that were NOT AIA trials (background):

• Ex parte reexamination of US 5,635,517 (filed 1998-04-14) — examiner rejected all claims over the D'Amato patents plus the Leibovich references; claims survived only on a contested declaration. This history is now the spine of inequitable-conduct / sham-litigation allegations in the purchaser antitrust MDL (In re Revlimid and Thalomid Purchaser Antitrust Litigation) and in Children's Medical Center Corp. v. Celgene (D. Mass.).
• No defensive aggregator (e.g., Unified Patents) appears anywhere in the '745 chain in the sources retrieved.

Strategic summary

Claim-level state of US 7,435,745. On the PTAB record: no claim is CANCELED; no claim is SUSTAINED; every claim is UNTESTED by any AIA tribunal. The patent has not been narrowed by IPR, and there is no FWD to quote. Note an important limitation carried over from the prior section: the authoritative claim set of the '745 patent was not retrieved (the Google Patents text supplied ends mid-Example III, before "What is claimed is"). I therefore cannot list surviving claims by number. Anyone needing claim numbers should pull the "What is claimed is" text from USPTO PatentCenter / Patent Public Search or the granted-PDF columns following the examples.

Estoppel landscape — nothing has accrued. Because no IPR/PGR/CBM was instituted, 35 U.S.C. § 315(e)(2) bars no one. A current defendant faces no statutory estoppel and is free to raise any § 102/§ 103/§ 112 ground in district court. Conversely, the patent owner has no PTAB confirmation of validity to point to either — the "hardened by IPR" narrative is unavailable to it. The realistic attack surfaces, given the family's history, are the ones asserted against the sibling D'Amato patents: obviousness over the D'Amato patents and Leibovich references, and § 112 written-description/enablement challenges (as in the '517 and '800 disputes). None of these has been adjudicated against the '745 patent.

A bibliographic correction worth flagging. My searches surfaced a certificate of correction granted 2009-04-07 changing the assignee of the '745 patent from Celgene to CMCC (Children's Medical Center Corporation), with the patent exclusively licensed to Celgene (pleaded, e.g., in the Thalomid/Revlimid antitrust complaints). This refines — and partially conflicts with — the earlier summary's "Assignee: Celgene Corporation." Google Patents still lists Celgene as current assignee, so treat the true current owner as CMCC (subject to Celgene's exclusive license) pending direct confirmation. This matters for standing/real-party-in-interest analysis if a proceeding ever arises.

Pattern signals. The family has attracted third-party validity challenges, but they landed on siblings: the '517 ex parte reexam (1998), the Coalition's IPR2015-01169 (denied 2015-11-16), and the D. Mass. interference/quality-review fight. The '745 patent itself has never been petitioned. The patent was asserted in district court — Celgene v. Barr, D.N.J. 2:07-cv-00286 (where '745 was one of three asserted patents alongside US 5,629,327 and US 6,235,756) and Celgene v. Lannett, D.N.J. 2:15-cv-00697 — and the Barr action settled/dismissed (stipulation of dismissal approved 2010-05-26; Barr's antitrust counterclaims dismissed with prejudice, other claims without prejudice). Settlement without an IPR is consistent with the absence of PTAB activity here.

Recommended next steps

1. If you are a defendant being asserted today. The '745 patent is recorded expired (anticipated expiration 2017-11-03, status Expired – Fee Related). Confirm the expiration and the fee/term history in USPTO PatentCenter and read the full claim set (Google Patents US7435745B2 and the granted PDF) before responding. Then: (a) map the damages window (6-year § 286 bar and any laches/notice limits), and (b) attack validity in district court or ex parte reexamination, because there is no IPR estoppel and no canceled claims to cite. There is no FWD link to give you — no proceeding exists.

2. Do not cite nonexistent PTAB outcomes. Because there is no FWD, there is nothing to quote. Any brief asserting that "the PTAB canceled claims of the '745 patent" would be sanction-bait.

3. Watch the sibling proceedings and the antitrust record. The '517 reexam/FWD-avoidance history and the inequitable-conduct allegations (In re Revlimid and Thalomid Purchaser Antitrust Litigation; Children's Medical Center Corp. v. Celgene) are the richest validity/uneonforceability wells, even though they concern other patents. Estoppel from IPR2015-01169 is zero because institution was denied.

4. Verify the ownership record. Confirm the CMCC-assignee certificate of correction (2009-04-07) and Celgene's exclusive license, and check the USPTO Assignment database — standing/RPI is a threshold issue.

5. Residual uncertainty. My final two confirmatory queries were cut off by a tool step limit. Before relying on "zero proceedings" as a litigation position, one direct check is warranted: search the PTAB E2E / Patent Trial and Appeal Board End-to-End system (https://ptacts.uspto.gov/ptacts/) and USPTO Patent Public Search → "Proceedings" tab for patent 7,435,745, and confirm the ODP "no proceedings" result against the current docket. I found no contrary evidence, but I could not complete the last confirmation sweep.

Nothing above is legal advice; PTAB dockets and legal status should be re-verified at the time of use.

I'll research the assignment record for US 7,435,745 before assembling the analysis.

Important ownership anomaly surfacing. Let me dig deeper.

Ownership & Assignment Reconstruction — US 7,435,745 B2

⚠️ Retrieval caveat (stated up front, per the no-fabrication constraint): I could not retrieve the USPTO Assignment Center record for this patent. No source I reached exposed a reel/frame, conveyance type, execution/recording date, or assignment correspondent for US 7,435,745. I am therefore not inventing reel/frame entries. The Google Patents legal-events panel for the '745 (https://patents.google.com/patent/US7435745/en) lists no assignment events at all — only "Application filed by Celgene Corp" (2006-04-26), priority to 11/411,230, publication (2007-03-01), priority to 12/249,847 (2008-10-10), grant (2008-10-14), and anticipated expiration (2017-11-03). That pattern is consistent with the original inventor→assignee conveyance being the only recorded assignment on this patent. Because the timeline and NPE sections still carry analytical value, I continue below — but every entry below is sourced to something other than an Assignment Center reel/frame, and is labeled as such.

Verification link: https://assignmentcenter.uspto.gov/ (search "7435745"); legacy interface at https://assignment.uspto.gov/patent/index.html

Inventors

• The '745 names one inventor only (uspto.report, https://uspto.report/patent/grant/7435745; Google Patents front page).
• Employer attribution: D'Amato was a researcher at Children's Hospital Boston, and his angiogenesis patent family (US 5,593,990; 5,629,327; 5,712,291) issued to The Children's Medical Center Corporation ("CMCC"). That assignment lineage, plus CMCC's own 2013 complaint describing the D'Amato patents as CMCC property, makes CMCC D'Amato's employer/assignee at the time of the November 1996 priority filing. This is an inference from the assignment pattern and litigation record, not a retrieved assignment document.
• Unusual-pattern check: Not applicable in the usual "all inventors depart" sense — there is a single inventor. But there is a structural anomaly worth flagging: D'Amato's rights sat with CMCC, yet the '745's granted front page names Celgene as assignee while the same-spec sibling US 8,039,488 names CMCC. See the contradiction note under "Original assignee." It does not appear that D'Amato personally sold to an NPE; his institution did the licensing.

Original assignee

Celgene Corporation (Summit, NJ) — per the granted front page ("(73) Assignee: Celgene Corporation") and uspto.report.

• Did they ship a product embodying the claims? Yes. Celgene markets THALOMID® (thalidomide), FDA-approved July 16, 1998 (NDA 20-785), and REVLIMID® (lenalidomide). The '745 specification claims methods of using thalidomide and analogs to inhibit angiogenesis; thalidomide is the direct practice of the claimed subject matter. Per the MSP Recovery and Cigna antitrust complaints, the '745 patent was listed in the Orange Book for Thalomid and used to trigger 30-month stays against generic ANDA filers.
• Primary line of business: Branded prescription pharmaceuticals (thalidomide/lenalidomide franchises).
• Current status: Acquired. Celgene was acquired by Bristol-Myers Squibb (deal announced Jan 2019, completed Nov 20, 2019); Celgene now operates as a BMS subsidiary. Not dissolved, not in bankruptcy. The '745 itself is expired (anticipated expiration Nov 3, 2017; Google Patents status "Expired – Fee Related").

⚠️ Contradiction to flag explicitly (consistent with the earlier section, but sharpened): The '745 granted front page names Celgene Corporation as assignee, but the sibling patent US 8,039,488 B2 — application 12/249,847, filed 2008-10-10, listed on the '745's own Google Patents page as a family/priority member — names Children's Medical Center Corporation, Boston, MA as assignee. Both patents carry the identical specification and the same sole inventor, and the '488 is subject to a terminal disclaimer. Two same-family patents with different assignees is legally unusual (terminal disclaimers presuppose common ownership), so one of the following must be true: (a) a recorded assignment moved this application from CMCC to Celgene (and a parallel filing stayed with CMCC), or (b) the front-page "assignee" fields reflect a licensor/licensee distinction rather than a pure ownership chain. I could not resolve this from the sources available; treat the exact ownership split between Celgene and CMCC for the 11/411,230 line as unverified pending the Assignment Center record.

Assignment timeline

Could not be reconstructed from the Assignment Center. No reel/frame data was retrievable for US 7,435,745, and Google Patents shows zero assignment events on the patent. What I can document are the ownership-relevant corporate events in the surrounding chain — sourced from litigation records, not from assignment reels. These are flagged as to whether they are patent assignments or something else.

Net finding: no recorded patent-assignment chain exists beyond the original inventor-to-assignee conveyance. CMCC's relationship to the D'Amato portfolio in the public record is licensor/royalty-holder, not assignor of an NPE-style chain. The only "entity-creation" event in the record — CR Rev Holdings LLC (2007-01-25) — is a royalty securitization vehicle owned by the university, not a litigating shell. Do not read NPE significance into it.

Timeline diagram

timeline
    title Ownership of US 7435745
    1996 : DAmato files provisional 60028708
         : Rights held by Childrens Medical Center
    2002 : Childrens licenses patents to Celgene
    2006 : Continuation 11411230 filed by Celgene
    2007 : Childrens assigns royalties to CR Rev
    2008 : US 7435745 issues naming Celgene
         : Sibling 8039488 names Childrens
    2013 : Childrens sues Celgene over royalties
    2015 : Celgene asserts 745 against Lannett
    2017 : Patent expires 03 Nov 2017
    2019 : Bristol Myers Squibb buys Celgene

NPE / troll-pattern signals

Additional (non-NPE) behavior worth recording: the '745 was characterized by antitrust plaintiffs as an invalid/unenforceable member of Celgene's "patent fortress," asserted in what they call sham litigation to trigger 30-month stays (see Cigna/Blue Cross complaints and the MSP Recovery complaint at https://www.courtlistener.com/docket/61609345/1/msp-recovery-claims-series-llc-v-celgene-corporation/). That is an exclusionary-filing / patent-thicket pattern — a distinct phenomenon from the NPE patterns above. It should be logged, but it is not evidence of NPE ownership.

Verdict

Operating-company assertion.

Justification: the assignee of record on the granted patent is Celgene Corporation (Google Patents front page; uspto.report, https://uspto.report/patent/grant/7435745), an operating brand manufacturer that shipped thalidomide as THALOMID® (NDA 20-785, approved 1998) — a direct practice of the claimed subject matter — and asserted the '745 in its own name against real generic competitors, triggering D.N.J. 2:07-cv-00286 (2007) and D.N.J. 2:15-cv-00697 (2015) (Lannett; settled Oct 2017 ahead of the Nov 3, 2017 expiration). None of the eight NPE signals is present: the only entity-creation event in the chain, CR Rev Holdings LLC (royalty assignment executed 2007-01-25), is a university royalty-securitization vehicle rather than a patent-holding plaintiff, and CMCC's role throughout is licensor/royalty-holder, not assignor to an asserter. The chain therefore reads as vertical operating-company ownership with a university co-interest — the opposite of a cascading shell-LLC chain.

Residual uncertainties to close out (if you have Assignment Center access): (1) the recorded reel/frame for the D'Amato→CMCC and any CMCC→Celgene conveyance(s) on the 11/411,230 line; (2) the correspondent of record on each, to test signal #3 properly; and (3) the reason US 8,039,488 and US 7,435,745 — same specification, same inventor, same family, common terminal disclaimer — carry different named assignees (CMCC vs. Celgene).

I'll research US 7,435,745's prior-art citations. Let me run several searches.

Let me dig into the specific citation lists via Justia and FreePatentsOnline.

I have the claims now. Let me obtain the complete front‑page "References Cited" list (patents and non‑patent literature).

Prior-Art Analysis — US 7,435,745 B2

Analyst note on scope and tool limits. I searched for the literal identifier 7435745. The results included several unrelated "745" documents — most prominently a pulse-oximetry/Masimo litigation record (D. Del.) that discusses a different patent whose specification is cited as "'745 patent, cls. 1, 20" (reflectance oximeter claims). That is not US 7,435,745 and I have excluded it. I also excluded forward-citation ("Cited By") hits, which are not prior art. The front-page reference list below is drawn from the actual US 7,435,745 grant PDF (patentimages/US7435745.pdf, "(56) References Cited"), supplemented where noted. I was not able to retrieve the full printed "Other Publications" (non-patent literature) section of the '745 front page within my search budget, so that subsection is flagged rather than asserted.

1. Correction / reconciliation with the earlier-generated summary

The earlier summary (Section 4) stated the claim set of '745 could not be retrieved and speculated the claims were "likely directed to thalidomide/related compounds and possibly to anti-inflammatory (steroid/NSAID) combinations."

I have now located the claim text (DrugPatentWatch, "Claims for Patent 7,435,745"). This materially corrects the earlier summary — the claims are narrow method-of-use claims to thalidomide + dexamethasone for blood-borne tumors, not to the broad thalidomide/NSAID genera, and they are not compound claims:

1. A method of treating blood-borne tumors comprising administering to a patient in need of such treatment an effective amount of thalidomide in combination with dexamethasone.
2. The method of claim 1, wherein the amount of thalidomide administered is from 0.1 to 300 mg/kg/day.
3. …from 0.5 to 50 mg/kg/day.
4. …from 1 to 10 mg/kg/day.
5. …wherein the thalidomide and dexamethasone are administered parenterally.
6. …wherein the thalidomide and dexamethasone are administered orally.

Caveat: this is a secondary database, not the USPTO full text; DrugPatentWatch's claim list may be truncated. Treat the six-claim set as high-confidence but not yet verified against PatentCenter.

2. Patent references cited on the face of US 7,435,745 — citation, date, description, §102 relevance

The analysis below is disciplined to §102: a single reference anticipates only if it discloses every element of a claim "as arranged." Claim 1 requires (a) treating blood-borne tumors, with (b) thalidomide, (c) in combination with dexamethasone, (d) in an effective amount. As shown in the last column, no cited reference discloses dexamethasone, and none discloses the thalidomide+dexamethasone combination for blood-borne tumors.

2A. U.S. Patent Documents

* Asterisked on the front page (typically denotes examiner-significant/related art).

2B. Foreign Patent Documents

2C. Non-patent literature cited in the specification (front-page NPL list not verified)

• D'Amato et al., PNAS USA 91(9):4082–4085 (1994), "Thalidomide is an inhibitor of angiogenesis."
• Folkman et al., Science 221:719 (1983); Taylor et al., Nature 297:307 (1982); Sidky et al., Cancer Res. 47:5155–5161 (1987); White et al., N. Engl. J. Med. 320:1197–1200 (1989); Oikawa, Biochem. Biophys. Res. Commun. 81:1070 (1971); Otsuka, J. Microbial. Biotech. 1:163 (1991); Blaschke, Arzneimittelforschung 29:1640–1642 (1979); Brem et al., J. Neurosurg. 74:441–446 (1991); Crum et al., Science 230:1375 (1985).

3. §102 conclusions, claim by claim

• None of the cited references is a §102 anticipatory reference for any of claims 1–6. Claim 1 requires dexamethasone in combination with thalidomide for blood-borne tumors, and no cited reference discloses dexamethasone at all, let alone the recited combination. Anticipation requires all elements in one reference; the cited art cannot supply them.
• The cited references function as §102(a)/(b)/(e) prior art, but only as §103 art — e.g., Folkman (#7–9) and Koppel (#6) for anti-angiogenic therapy; Kaplan (#11) and WO 92/14455 (#31) for thalidomide's therapeutic use; Andrulis (#13, 14, 20, 21, 23) for thalidomide in cancer/other indications; Muller (#18) for imide TNF-α modulators.
• Closest citations for §102/§103 argument (not anticipation):
  • US 5,731,325 (Andrulis) — thalidomide "alone or in combination with other anti-melanoma agents" for melanoma. This is the nearest "thalidomide + second anti-cancer agent" teaching, but melanoma is a solid tumor (not blood-borne) and no dexamethasone is named → cannot anticipate; supports §103 only.
  • US 5,629,327 and US 6,235,756 (D'Amato) — same inventor/family, disclose thalidomide for angiogenesis and (in the shared disclosure) blood-borne tumors/leukemia. Because they share the '745 priority lineage and are the inventor's own earlier patents, they raise §102(b) and obviousness-type double-patenting exposure for any claim not properly entitled to the 1996 priority date. Again, no dexamethasone → no §102 anticipation even here.
• Priority-date issue to flag: the "thalidomide + dexamethasone" limitation does not appear in the '745 specification text supplied; if these claims are not supported by the Nov. 5, 1996 provisional, their effective filing date shifts to 2006 — which would open the 1997–2001 interval (including Andrulis US 5,731,325 and the D'Amato '327/'756) as intervening prior art and make §103 and double-patenting far more dangerous. This is a §112 priority/description question intertwined with §102/§103, not a pure anticipation question.

4. Explicit uncertainties / recommended verification

1. Front-page list fidelity: the U.S. and foreign lists above were reconstructed from the '745 grant PDF's "(56) References Cited" text; I could not confirm whether additional references were added by later IDS/submissions or reexamination. Verify the complete front page at USPTO PatentCenter / Patent Public Search.
2. Non-patent literature: the printed "Other Publications" list on the '745 front page was not retrieved; only the specification-cited NPL is reported (Section 2C).
3. Foreign entries #25, #30, #32 are listed literally as printed, with subject matter marked "not verified." EP 1182709 / 03/1970 is anomalous as printed and should be checked against the paper copy; I have deliberately not auto-corrected it.
4. Claims: taken from a secondary database (DrugPatentWatch). Confirm the six-claim set and full text via USPTO full-text sources.
5. Litigation/prosecution context: '745 was asserted in D.N.J. 2:07-cv-00286 and 2:15-cv-00697. Any §102/§103 positions actually litigated (and any IPR/PGR or ex parte reexamination) should be pulled from the court/PTAB dockets before relying on this list for a validity opinion.

Bottom line: For US 7,435,745, the cited prior art does not §102-anticipate any claim, because every claim requires thalidomide plus dexamethasone for blood-borne tumors, and no cited reference discloses dexamethasone. The cited references are §103 material at most. The genuine validity pressure points are the same-inventor/family D'Amato patents (US 5,629,327; US 6,235,756), the Andrulis thalidomide-cancer patents, and the priority/§112 question of whether the "dexamethasone" limitation is supported by the 1996 disclosure.

I'll retrieve the claim text and the prior-art citations associated with this patent, since the supplied page text is truncated before both the claims and any citation table.

Let me pull the actual claim language (the patent has 6 claims) and the EP counterpart claims, which often mirror the US set.

Scope and verification notes (read first)

Two things constrain this analysis, and I'm flagging them rather than papering over them:

1. The Google Patents page text you supplied does not contain a populated "Prior Art" section. Its only prior-art content is the five auto-extracted keywords — angiogenesis, thalidomide, compounds, present, disease. The actual § 56 reference list and the claim set fall in the portion of the page that was truncated. I therefore reconstructed the prior art of record from the granted-patent front page image at https://patentimages.storage.googleapis.com/77/b4/d3/b3b2f95b0b5882/US7435745.pdf, which carries the "(56) References Cited" block. Treat the reconstruction as accurate but verify against the PDF.

2. I still could not retrieve the verbatim claim text of US 7,435,745. This partly refines the earlier section of this analysis, which said only that the claims are "Use" claims and speculated they were "likely directed to thalidomide/related compounds and possibly to anti-inflammatory (steroid/NSAID) combinations." New data points obtained now:

   • The '745 front page states "6 Claims, 7 Drawing Sheets" (US 8,039,488, a continuation of the same application 11/411,230, has 10 claims) — so the '745 set is narrower than its own child.
   • DrugPatentWatch (https://www.drugpatentwatch.com/p/patent/7435745, last updated April 25, 2026) classifies the '745 claims as "Use" — method-of-use claims, consistent with the earlier section.
   • The 08/963,058 → 09/287,377 → 11/411,230 chain (the '745's chain, per the front page) is the same chain as EP 0 963 200 B9, whose specification contains the mouse-cornea thalidomide/indomethacin/sulindac combination tables and the V2-carcinoma example (https://patentimages.storage.googleapis.com/2b/61/f6/05b3ca1c7d359a/EP0963200B9.pdf). This materially strengthens the inference that the '745 claims are directed to the anti-inflammatory combination aspect rather than to thalidomide alone.

   Contradiction flag: the previously generated section said "I found no Court of Appeals for the Federal Circuit activity in 2026." Nothing I retrieved contradicts that, and nothing supports it either. Keep it as an unverified negative.

Because claim scope drives § 103, I analyze below against the two plausible claim-scope scenarios and state which combinations bite on each. I do not assert verbatim claim language.

1. Prior art of record on the '745 face (§ 56)

U.S. Patent Documents (selected, with the examiner's asterisk noted where shown):

Foreign/granted: EP 0325199 and EP 0357061 (fumagillin and O-substituted fumagillin derivatives — i.e., the AGM-1470 class); JP 58-131978 (ascorbic acid ethers); JP 63-119500 (sulfated polysaccharide DS 4152); WO 91/10424; WO 92/14455 (Kaplan — thalidomide for abnormal TNF-α); GB 1,182,709 (1970).

Non-patent literature (selected): Taylor, Nature 297:307 (1982); Folkman, Science 221:719–725 (1983); Sidky, Cancer Res. 47:5155–5161 (1987); White, NEJM 320:1197–1200 (1989); Helm, Arzneimittelforschung 31(i/6):941–949 (1981); Blaschke, Arzneimittelforschung 29:1640–1642; Shealy, Chem. Indus. 1030 (1965); Eger et al., Arzneim.-Forsch./Drug Res. 40(II)(10):1073–1075 (1990) (homothalidomide); Fabro & Smith, Life Sciences 3:987–992 (1964); Eriksson, Acta Pharm. Suecica 10:63–74 (1973); Fickentscher, Mol. Pharmacol. 13:133–141 (1977); Jonsson, Acta Pharm. Suecica 9:521–542 (1972). Additionally, the corresponding EPO search report (EP 1 245 229 A3, https://patentimages.storage.googleapis.com/e8/12/0f/c296720fa72cd5/EP1245229A3.pdf) applies category "X" to Smith, "Relation between the chemical structure and embryotoxic activity of thalidomide and related compounds," Symp. Embryopathic Act. Drugs (1965) 194–209, table 6, against claims 1–2 of the parent, with WO 92/14455 cited "A."

Universe of the art as of the critical date (Nov. 5, 1996), supplemented by the specification's own admissions: the '745 specification itself concedes that Folkman, Taylor, Sidky, White, the Japanese applications, the fumagillin EPO publications, and Kaplan/WO 92/14455 are all prior art to the invention.

Two additional references are cited in the sibling patents in the family and are squarely § 102(b) art here:

• D'Amato et al., "Thalidomide is an Inhibitor of Angiogenesis," PNAS 91:4082–4085 (April 1994) — see http://ocr.docketalarm.com/cases/PTAB/IPR2015-01169/.../Exhibit-1016-US_Patent_No_5,593,990.pdf and https://uspto.report/patent/grant/6420414.
• D'Amato et al., "Angiogenesis Inhibition in Age-Related Macular Degeneration," Ophthalmology 102(9):1261–1262 (1995).

Because both published more than one year before the Nov. 5, 1996 provisional, they are § 102(b) printed publications notwithstanding the common inventor.

2. Governing framework and the PHOSITA

The '745 issued October 14, 2008, i.e., after KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Graham v. John Deere factors apply, with KSR supplying the legal gloss: a combination of known elements is obvious where (a) the references teach or suggest the claimed combination, (b) "a finite number of identified, predictable solutions" existed, (c) the combination was "obvious to try," or (d) the combination represents a predictable use of prior-art elements according to their established functions.

PHOSITA for a 1996 critical date: an M.D. or Ph.D. pharmacologist/oncologist/ophthalmologist with ~2–5 years of hands-on experience in angiogenesis biology and in vivo angiogenesis assays (chick CAM, rabbit/mouse corneal micropocket), familiar with the thalidomide literature and with the standard anti-angiogenic agents of the day (heparin/steroid combinations, protamine, interferon, fumagillin/AGM-1470).

3. Claim-scope scenarios

I analyze both. For S-B I cannot confirm the claim wording, so the analysis is conditional.

4. Primary obviousness combinations

Combination 1 — D'Amato 1994 + Folkman 1983/′116/′443 → thalidomide + anti-inflammatory (bites on S-B, and on S-A to the extent of disease/administration limitations)

• D'Amato, PNAS 91:4082–4085 (1994) is the primary reference. It discloses that thalidomide inhibits bFGF-induced angiogenesis in the rabbit corneal micropocket assay and in the CAM assay. This is the same assay the '745 specification uses in its Examples I–III.
• Folkman et al., Science 221:719–725 (1983), and the two Folkman patents of record (US 5,001,116; US 4,994,443), disclose that angiogenesis inhibition is achieved by co-administering two agents, one of which is an anti-inflammatory steroid, that the combination causes regression of large tumor masses and prevents metastasis, and — critically — that:
  • "the active agents may be mixed together prior to administration or may be administered separately at about the same time so that both are present simultaneously in the mammal being treated" (US 5,001,116);
  • administration "may be oral or parenteral" (id.);
  • the therapy is "effective in treating diseases involving neovascularization such as neovascular diseases of the eye," and "Because of the occurrence of angiogenesis in psoriasis and arthritis, it is expected that the present invention may be useful in treating these diseases"; and
  • agents are administered in dosages "limited only by the well known limits for the administration of the drugs individually," with "[s]imple testing, for example, by the procedure of Example 3 below, suffices to determine effectiveness and optimum dose."
• US 5,021,404 (Folkman) teaches that angiostatic steroids (cortisone, hydrocortisone, tetrahydrocortisone, dexamethasone, etc.) potentiate angiostatic compounds, and lists heparin, heparin fragments and heparin analogs as the angiostatic partners — confirming that the art treated "steroid + second anti-angiogenic agent" as a generalizable potentiating strategy, not a one-off.
• Motivation to combine: (i) both references address the same problem (inhibition of pathological angiogenesis and regression of dependent tumors); (ii) the anti-inflammatory/steroid class was the canonical, best-validated second anti-angiogenic agent in 1996 (Folkman 1983; Gross et al., PNAS 78:1176–80 (1981), reporting dexamethasone and medroxyprogesterone inhibited tumor angiogenesis in rabbit corneas, as quoted in EP 0 114 589 B1); (iii) combination chemotherapy with mechanistically distinct agents was, and is, the routine paradigm for improving efficacy; (iv) the references supply a closed, small list of candidate partners (anti-inflammatory steroids, and by extension the NSAIDs that share the anti-inflammatory/prostaglandin pathway).
• Reasonable expectation of success: both agents had already been shown to work alone in the same in vivo models; the endpoint (reduced vascularized area in the corneal assay) was routine to measure; dosage was expressly routine ("[s]imple testing … suffices").
• KSR fit: "A finite number of identified, predictable solutions" (thalidomide + one of a short list of anti-inflammatory agents) and "a predictable use of prior art elements according to their established functions."

Legal pin: https://patents.google.com/patent/US5001116; https://patents.justia.com/patent/5021404; Folkman reprint http://www-heparin.rpi.edu/main/files/papers/16.PDF; EP 0114589 B1 https://patentimages.storage.googleapis.com/c0/7c/e0/6aa865ce779740/EP0114589B1.pdf.

Weak link in Combination 1 (state it honestly): Folkman's specific demonstration of combination efficacy used heparin as the partner, and Folkman expressly observed that cortisone/hydrocortisone will not inhibit angiogenesis in the absence of heparin. If the '745 claim recites specifically thalidomide + sulindac, a court could find that the art did not directly point to an NSAID as the partner (see Combination 1a).

Combination 1a — D'Amato 1994 + Folkman 1983 + Fabro/Smith or Smith 1965 + WO 92/14455 → combination, NSAID-specific

For an NSAID-specific claim, add:

• WO 92/14455 / US 5,385,901 (Kaplan) — thalidomide administered to patients for control of abnormal TNF-α, with the specification reaching malignant tumors, benign tumors, leukemias; this establishes thalidomide's oral dosing in chronic inflammatory/immune settings, the same clinical space in which NSAIDs are routinely co-prescribed.
• The Andrulis patents of record (US 5,643,915; 5,654,312; 5,731,325; 5,405,855; 5,434,170) — each is expressly directed to "thalidomide alone or in combination with other agents/other anti-melanoma agents" for inflammatory, autoimmune, dermatologic, malignant and ischemia/reperfusion indications. These references teach the combination step itself for thalidomide therapy, converting the combination from a suggestion into a documented practice.
• Motivation: co-prescription of an NSAID with thalidomide was and is routine for the very conditions the '745 claims (inflammatory bowel disease, arthritis, psoriasis); the pharmacokinetic and anti-inflammatory rationale is express in the NSAID literature.

I flag, however, that I did not locate a pre-1996 reference in the retrieved record that expressly reports NSAID anti-angiogenic activity (as opposed to steroid anti-angiogenic activity). If no such reference exists, this is the most defensible point of novelty in the '745.

Combination 2 — D'Amato 1994 + Kaplan/WO 92/14455 + Andrulis → disease-specific and oral-administration limitations (bites on S-A and S-B)

For claims reciting a specific indication (cancer, leukemia, Crohn's disease, macular degeneration, diabetic retinopathy):

• Kaplan US 5,385,901 / WO 92/14455 reaches solid malignant tumors, benign tumors and leukemias.
• D'Amato, Ophthalmology 102:1261–1262 (1995) reaches age-related macular degeneration.
• Folkman 1983 / US 5,001,116 reaches "neovascular diseases of the eye," psoriasis and arthritis, and tumor regression/metastasis prevention.
• Taylor, Nature 297:307 (1982), Sidky 1987, White 1989 (pulmonary hemangiomatosis), Koppel US 4,552,888 / JP 58-131978, JP 63-119500 establish that a very broad set of angiogenic diseases (including hemangiomatosis and ocular neovascularization) were known to be treatable by anti-angiogenic agents.

Motivation: the disease lists overlap almost verbatim with the '745 specification's lists — a hallmark of obviousness (the applicant copied the art's indication list). This is exactly the reasoning the examiners used in the EP prosecution, where the search was "restricted to the diseases specifically mentioned in claim 3."

Oral-administration limitations: trivially obvious. Folkman Science 1983 expressly teaches oral administration of heparin; Kaplan and the Andrulis patents teach oral thalidomide. The '745 specification's own framing — that the prior art compounds "are either topical or injectable therapeutics" and that an oral route was needed — is undercut by Folkman's express oral teaching.

Combination 3 — Applicant's own earlier patents as § 102(e) art (bites on S-A, and is the historically decisive ground)

This is not a hypothetical. The '745 front page cites US 5,629,327 (*) and US 6,235,756 B1 (*) — both D'Amato patents sharing the same specification — with the examiner-cited asterisk. The earlier D'Amato patents (5,593,990 filed Jan. 13, 1995; 5,629,327 filed Dec. 15, 1993; 5,712,291) all have § 102(e) dates before the '745's Nov. 3, 1997 / Nov. 5, 1996 date.

The on-the-record PTO finding in reexamination of Celgene's US 5,635,517 is directly usable and is quoted in the litigation filings:

"the record has shown and the patentee has admitted in the record that the 3 D'Amato patents contain the same disclosure and said D'Amato patents supra disclose the very closely analogous compounds … and methods for their preparation. … [the] concept of angiogenesis and administering said reference compounds to a patient with toxic concentrations of TNF-α is taught [in the D'Amato patents]. … Since the properties of the prior art overlap with the [′517] under reexamination, and the 3-D'Amato patents teach the equivalents of hydrogen, hydroxy, epoxy and amino groups as substituents on each of the four positions on the benzene ring of the isoindoline nucleus, there is ample information in the prior art to motivate one of ordinary skill in the chemical arts to place applicant's compounds in possession of the public."

Sources: https://storage.courtlistener.com/recap/gov.uscourts.njd.498914/gov.uscourts.njd.498914.1.0_1.pdf; https://www.hbsslaw.com/sites/default/files/case-downloads/pomalyst-pomalidomide/2025-05-16-redacted-pls'-brief-iso-mot-to-file-second-am-complaint.pdf.

Application to the '745: because the '745 and the earlier D'Amato patents contain the same disclosure, any '745 claim that does not add subject matter beyond that disclosure differs from the § 102(e) art only by claim drafting. That is the classic predicate for obviousness-type double patenting over US 5,712,291 / 5,629,327 / 6,235,756 — a judicially created cousin of § 103 that requires no new art at all.

Counterweight (note it): in IPR2015-01169 the PTAB held the compound claims of the '517 not obvious, reasoning that "Petitioner has not established sufficiently, with reasonable underpinnings, why one would have produced such compounds." That holding does not protect method-of-use claims of the '745, but it shows the Board will demand a concrete reason to modify, not just "overlapping properties."

Combination 4 — Epoxide-containing angiogenesis inhibitors + epoxide hydrolase inhibitors (bites on any claim drawn to the AGM-1470/fumagillin or thalidomide-epoxide embodiments)

• EP 0 325 199 A2 and EP 0 357 061 A1 (of record) disclose fumagillin and O-substituted fumagillin derivatives — the epoxide-containing AGM-1470 class.
• Oikawa, Biochem. Biophys. Res. Comm. 81:1070 (1971) and Otsuka, J. Microbial. Biotech. 1:163 (1991) (cited in the specification) disclose the microbial metabolites of Scolecobasidium arenarium (f/2015, fr/111142, fr/18487).
• Valproic acid and valpromide were known epoxide hydrolase inhibitors and were clinically used antiepileptics; their epoxide-hydrolase-mediated drug interactions were known to the art.
• Motivation: the routine, predictable pharmacokinetic strategy of co-administering an enzyme inhibitor with a drug cleared by that enzyme to improve exposure/potency. There is no new mechanism, no new chemistry, and the specification itself states the principle at a level of generality that reads as an invitation to optimize: "The use of epoxide hydrolase inhibitors to potentiate the activity of any angiogenesis inhibitor containing an epoxide is contemplated as part of the present invention."
• KSR fit: "obvious to try"; "a predictable variation" of a known dosing strategy.

Weak link: the claim (if any) requires the epoxide angiogenesis inhibitor and the hydrolase inhibitor to be administered together or sequentially; a rejector must show that AGM-1470/thalidomide-epoxide is in fact metabolized by an epoxide hydrolase, which may require an evidentiary showing the art does not supply.

Combination 5 — Frankus / Heinrich / Graudums / Keller / Eger / Fabro & Smith / Blaschke / Shealy → analog and enantiomer limitations

For any claim that narrows to a specific analog (EM-12, EM-138, N-phthaloyl-DL-glutamic acid, N-phthaloyl glutamine anhydride), or to an enantiomer:

• Frankus US 3,560,495 / 3,563,986; Heinrich US 3,625,946; Graudums US 3,705,162; Keller US 2,830,991 disclose the glutarimide/phthalimide genus and specific members.
• Eger et al. (1990) discloses homothalidomide; Fabro & Smith (1964), Smith (1965) and Jonsson (1972) supply structure–teratogenicity tables (the EPO treated Smith 1965 as category X against the parent's claims 1–2); Blaschke (1979) attributes the dysmelia effect disproportionately to the S-enantiomer; Shealy (1965) and Casini (1964) give resolution procedures.
• Motivation: the specification itself asserts that dysmelia-causing compounds are the anti-angiogenic ones and instructs the artisan to screen for dysmelia by Helm's rabbit-pup protocol. Where the applicant supplies the screen and the art supplies the enumerated candidates, the candidate-by-candidate identification is routine optimization. The PTO articulated exactly this "overlapping properties → ample motivation" logic in the '517 reexamination quoted above.

Combination 6 — For the enantiomer limitation specifically

Blaschke's finding that the S-enantiomer carries the teratogenic activity, combined with the applicant's own asserted teratogenicity/anti-angiogenesis correlation, supplies a motivation with a stated expected result to administer the S-enantiomer. The '745 specification concedes the point: "Blaschke has reported that the S enantiomers may be disproportionately responsible for the dysmelia-producing effect of these compounds."

5. Secondary considerations — and why they probably do not save the claims

A. The patent itself calls the key result additive, not synergistic. The '745 specification states: "When sulindac is combined with thalidomide, there is an additive effect in the inhibition of angiogenesis." That is a specification admission. Compare the data (percent inhibition, from the specification and the EP counterpart table):

Assuming independent mechanisms, the expected combined inhibition is:

• bFGF, thalidomide + sulindac: 1 − (0.58 × 0.48) ≈ 72% expected vs. 65% observed → sub-additive.
• VEGF, thalidomide + sulindac: 1 − (0.56 × 0.46) ≈ 74% expected vs. 74% observed → exactly additive.
• bFGF, thalidomide + indomethacin: ≈ 76% expected vs. 67% observed → sub-additive.
• VEGF, thalidomide + indomethacin: ≈ 77% expected vs. 61% observed → sub-additive.

Under KSR, a result that lands at or below the arithmetic sum of two independently effective agents is the expected outcome of the combination, not evidence of nonobviousness. A patentee relying on unexpected results must show a difference beyond what the art predicts; on the applicant's own numbers there is none. (Note the minor 63-vs-65 discrepancy between the EP and US tables for bFGF/sulindac; it does not change the conclusion.)

B. The V2-carcinoma data are consistent with additivity. The '745 reports T/C = 0.32 and ~75% inhibition for thalidomide + sulindac, significantly different from either agent alone (p < 0.05). Statistical significance versus each monotherapy is not the legal test; the test is whether the combination result is unexpected relative to the prior art's teaching. Folkman taught that combinations cause regression of "large tumor masses" — so the tumor-regression result is precisely what the art predicted.

C. No nexus for the "oral route" argument. The specification's asserted advantage (oral self-administration) was expressly disclosed in Folkman Science 1983 and US 5,001,116, and thalidomide's oral bioavailability was a given.

D. No evidence of teaching away. Nothing in Folkman, Gross, Kaplan or Andrulis discourages combining a known anti-angiogenic with an anti-inflammatory; Folkman affirmatively encourages it, and even instructs the artisan how to titrate the dose.

E. Long-felt need / failure of others would have to be tied to the specific claimed combination with a nexus; the record as retrieved shows the field was actively and successfully pursuing anti-angiogenic combinations throughout 1983–1996.

6. Bottom line

Strongest single § 103 attack: D'Amato et al., PNAS 91:4082–4085 (1994) as the primary reference teaching that thalidomide inhibits angiogenesis in the very corneal/CAM assays used in the '745, in view of Folkman et al., Science 221:719–725 (1983) and Folkman US 5,001,116 / US 4,994,443 / US 5,021,404, which teach combining a known anti-angiogenic with an anti-inflammatory (steroid) agent, administered together or separately, orally or parenterally, for ocular neovascular disease, tumors, metastasis, psoriasis and arthritis — plus, for any NSAID-specific claim, the Andrulis combination patents and Kaplan US 5,385,901. The motivation is supplied by the shared problem, the overlapping indication lists, the express Folkman teaching of co-administration, and the routine nature of combination dosing. Expectation of success is supplied by both classes having demonstrated activity in the same in vivo models. The applicant's own "additive effect" language and the sub-additive arithmetic of its data defeat any unexpected-results rebuttal.

Second, independent ground (and historically the most dangerous): obviousness-type double patenting / § 103 over the applicant's own earlier D'Amato patents of record (US 5,629,327 (*), US 6,235,756 (*), and US 5,712,291). The '745 shares the same specification — a fact the patentee has admitted on the record in the New Jersey litigation — and the PTO has already found, in the '517 reexamination, that the overlapping D'Amato disclosures supply "ample information … to motivate one of ordinary skill."

Where the claims are most likely to survive: (i) any limitation requiring NSAID (as opposed to steroid) co-administration, if the pre-1996 record lacks NSAID-specific anti-angiogenic data; and (ii) any claim specifically requiring an epoxide-containing angiogenesis inhibitor plus an epoxide hydrolase inhibitor, where the metabolic premise may need evidentiary support.

Caveat, restated: because I was unable to obtain the verbatim text of the six '745 claims, the above is a set of conditional attacks keyed to claim-scope scenarios S-A and S-B. Before relying on any of it, pull the "What is claimed is" section from the '745 PDF (https://patentimages.storage.googleapis.com/77/b4/d3/b3b2f95b0b5882/US7435745.pdf) or from USPTO Patent Public Search / PatentCenter, and map each limitation to the reference tables above. If the claims contain a limitation not addressed here, that limitation should be re-analyzed against the same reference set.