Patent: 10,018,625

Summary for Patent: 10,018,625

Title:	Use of female mammal\'s urine for determination of fetal gender related characteristics
Abstract:	The present invention provides a method for determining the gender of a fetus by assaying the sex hormones, evaluating the overall reducing/oxidizing (redox) activity, and/or evaluating the radical scavenging capacity of the maternal urine or other body fluid. The method can be used to determine fetal gender at any time point during the entire pregnancy. The body fluid may be processed before assaying. Processing may involve aging the body fluid, or purification of various fractions. The methods of the present invention also provide for a means for pre-conception offspring gender planning by assaying the sex hormones, evaluating the overall reducing/oxidizing (redox) activity, and/or evaluating the radical scavenging capacity of the urine or other body fluid from a non-pregnant female. The sex hormone profiles, the overall redox activity, and/or the radical scavenging capacity of a urine sample correlates with the gender specific compatibility of the ovum being released during a particular menstrual cycle. Therefore, assaying aforementioned parameters from a non-pregnant female\'s urine will help a couple or an animal breeder have an offspring of a desired gender. The present invention also provides a method of conceiving a baby of a desired gender in a female by applying to the female a pharmaceutical formulation with a specific sex hormone composition.
Inventor(s):	Verma; Kuldeep C. (Livonia, MI)
Assignee:	Urobiologics LLC (Livonia, MI)
Application Number:	14/312,534
Patent Claims:	see list of patent claims

Executive summary: US Patent 10,018,625 claims a urine-based, antibody-retained, redox-indicator readout method that links a “net redox activity” signature for estrogen, testosterone, progesterone, and hCG-beta to (i) fetal sex for a pregnant female and (ii) gender-specific compatibility for an ovum from a non-pregnant female. The estate is likely narrow on core inventive concept (redox readout tied to multi-hormone/hCG-beta antibody surfaces and comparison to standards), but extremely broad in implementation detail via extensive indicator, surface, and processing option claim coverage. Enforceability and freedom-to-operate will hinge on whether earlier art already disclosed (a) urine aging plus antibody capture of those analytes and (b) redox/FRAP/electrochemical readouts in a comparable diagnostic framework.

US Patent 10,018,625: What claims cover urine aging, antibody capture of hormones and hCG-beta, and redox indicator detection for fetal sex

What is claimed in US 10,018,625 (claims 1–32)

Claim 1 is the independent claim and defines the core combination:

• Sample: urine from (i) a pregnant female carrying an unborn child or (ii) a non-pregnant female for ovum compatibility.
• Aging: urine aged at ambient temperature for ≥ about 2 days.
• Capture surface: solid surface comprising antibodies specific to:
  • estrogen
  • testosterone
  • progesterone
  • hCG-beta
• Redox indicator: contacting the antibody surface with at least one redox indicator selected from:
  • sodium salicylate
  • methylene blue
  • a heteropoly acid or salt
  • chromogenic chemical
  • fluorophore
  • redox sensitive polymer
  • free radical
• Readout: detecting net redox activity of the retained estrogen/testosterone/progesterone/hCG-beta by a change in a chemical property of the redox indicator.
• Calibration: comparing net redox activity to a “known net redox activity” of a standard, where standards are from (a) another pregnant female with known fetal gender or (b) another non-pregnant female with known ovum compatibility.
• Determination: assigning fetal gender/ovum compatibility based on that comparison.

Dependent claims add breadth:

• Specific redox indicators: heteropoly acids including phospho-24-tungstic acid; chromogens including Fe(III)-TPTZ (FRAP-TPTZ chemistry) and potassium ferricyanide; free radical including hydroxyl radical; sodium salicylate or methylene blue as indicators.
• Specific assay modality: net redox activity measured by FRAP or FRAP-TPTZ; or by electrochemical sensor.
• Implementation formats: cover slips, slides, tubes, microtiter wells, chips, strips, membranes, films, fibers, plates, bottles, boxes; also particles.
• Timing windows: non-pregnant urine around ovulation/mid-cycle; pregnant urine from missed menstruation day 1 to 40 weeks, with dependent claim range 5–15 weeks.
• Fluorophores: GFP/EGFP/fluorescein derivatives.
• Processing steps: “processing prior to passing” with wide categories and expansive examples (adsorbents, precipitants, acids, enzymatic treatment, extraction, purification).
  • Example adsorbents include talc, silica gel, alumina, florisil, charcoal, kaolin, concanavaline A conjugates, calcium phosphate/hydroxide/chloride, CTAB, lectins, glassfiber filter, ion exchange resins, affinity ligands, solvents, solid phase extractants, size exclusion sieves, reverse phase chromatography.
  • Example precipitants include heavy metals (barium, lead, molybdenum, tungsten) and specific reagents (barium chloride/hydroxide, zinc chloride, mercuric chloride, lead acetate, ammonium sulphate, dextran, acetonitrile, chloroform, sodium hydroxide, trichloroacetic acid, potassium iodate; mixtures).
• Outcome mapping: net redox activity relative to standards indicates net oxidizing or net reducing activity and maps to male vs female gender/compatibility.

How the claim is structured for infringement

The independent claim is a method claim requiring all elements in combination: aging, urine-to-antibody solid phase contact, redox indicator use, detection of net redox activity tied to hormones/hCG-beta retained on the antibody surface, and comparison to standards for gender assignment. Dependent claims add alternative indicator/assay/processing options rather than requiring new intermediate steps in every case.

Practical infringement triggers:

• A system that does urine aging at ambient temperature for ≥2 days plus antibody capture of estrogen/testosterone/progesterone/hCG-beta plus a redox indicator readout plus comparison to previously characterized standards for gender assignment is strongly aligned to claim 1.
• A developer can attempt design-around by removing one or more of: (i) aging duration/conditions, (ii) the specific analyte panel and antibody capture, (iii) the redox indicator readout concept (as chemically defined), or (iv) the “net redox activity comparison to known standards” decision framework.

What the “net redox activity” definition does legally

Claim 1 frames net redox activity as “detected by a change in a chemical property of the at least one redox indicator.” That links the invention to a chemical transduction step rather than pure electrochemical sensing alone, although dependent claim 15 expressly allows an electrochemical sensor. The scope therefore likely covers both:

• indicator-based optical/colorimetric/fluorescent chemistries, and
• electrochemical readouts, provided they still operationalize the “redox activity” via the indicator change/response.

Claim coverage breadth created by alternatives

The dependent claims introduce many interchangeable components, expanding the set of covered embodiments:

• Multiple redox indicators and indicator classes (salicylate, methylene blue, heteropoly acids, chromogens, fluorophores, redox sensitive polymers, free radicals).
• Multiple readout assay archetypes (FRAP/FRAP-TPTZ, electrochemical).
• Multiple consumable formats (from microtiter wells to strips to chips; plus particles).
• Multiple sample acquisition timings (missed menstruation through gestational periods; ovulation/mid-cycle for non-pregnant use).
• Multiple sample preparation methods with extensive example lists.

This structure can complicate invalidity arguments because a challenger must show a single prior art disclosure that anticipates the full claim combination (for novelty) or shows a nonobvious path for the combination (for obviousness). But it also increases the probability that some element is already present in earlier diagnostics and could be used in an obviousness mosaic.

What patents protect urine-based fetal sex testing using hormone/hCG-beta antibodies and redox indicator readouts?

What patent landscape is implicated by the claim elements

US 10,018,625 spans several technical “clusters” that typically appear across different patent families:

1. Fetal sex determination from maternal samples (urine, blood, or other matrices) using biomarkers, immunoassays, and/or hormone panels.
2. Immunoassay capture of hormones and hCG variants (antibodies against estrogen, testosterone, progesterone, and hCG-beta).
3. Redox activity assays and redox indicator chemistry (including FRAP/TPTZ style chemistry, salicylate/methylene blue redox systems, heteropoly acids).
4. Urine sample handling and aging to modulate measurable properties.
5. Calibration/standard comparison frameworks for gender calls.

A credible freedom-to-operate and litigation assessment must identify earlier art that intersects multiple clusters rather than just one.

Which jurisdictions would matter for competitive clearance

The claim is a US patent (10,018,625), but infringement and licensing strategy also depend on parallel filings (if any) in:

• Europe (EP) and UK for similar claims,
• WIPO/PCT families affecting multiple countries,
• China (CN) and Japan (JP) for common immunoassay/diagnostics filing patterns,
• Canada (CA) if the family has North American breadth.

Without the patent family and prosecution history, the cross-jurisdiction landscape can’t be fully enumerated here.

When does US Patent 10,018,625 expire, and what does that mean for generic or noninfringing alternatives?

What is the expected expiration pathway

US utility patents generally expire 20 years from earliest effective non-provisional filing date, subject to adjustments and terminal disclaimers. Patent term is the key constraint for licensing and for determining whether competitors will rush or wait.

How exclusivity functions for a diagnostic method

There is no “Orange Book” exclusivity for method patents; the enforceability depends on:

• the patent claims’ validity and construction,
• whether competitors practice the full method (or an equivalent),
• and whether regulatory approval changes adoption timelines.

How strong is the patent estate for US 10,018,625 (claim scope, potential vulnerabilities, and enforceability signals)?

Strength factors created by the independent claim combination

The core combination is relatively specific:

• a particular analyte panel (estrogen, testosterone, progesterone, hCG-beta),
• on a multi-antibody solid phase,
• followed by a redox indicator-based “net redox activity” detection,
• with decisions made via comparison to gender-labeled standards.

If earlier art discloses fetal sex testing with hormones but not redox indicator measurement, it may not anticipate claim 1. If earlier art discloses FRAP or redox assays in urine but not antibody-retained multi-hormone/hCG-beta capture, it may also fall short.

Vulnerability factors created by “known chemistry” and broad alternatives

The claim deliberately broadens indicator selection and assays. That can create invalidity pressure if prior art already used:

• FRAP/TPTZ-like chemistry on biological matrices, and
• redox indicator systems like methylene blue or heteropoly acids, and
• antibody-based immunoassays for hormones including hCG variants.

In that scenario, a challenger can argue that it would have been obvious to substitute or combine known pieces into the claimed diagnostic workflow.

Method claim enforceability issues

Method claims are enforceable only against entities that perform the steps. For diagnostics, enforcement is often complicated by:

• who performs the full method (manufacturer vs lab vs user),
• whether any step is performed by a licensed service provider,
• and how step-by-step instructions map to actual lab protocols.

Claim 1’s “aging at ambient temperature for at least about 2 days” is a step that could be modified by competitors to avoid literal coverage, though doctrine of equivalents can still be argued depending on prosecution history.

What prior art could anticipate US 10,018,625 (and what elements would need overlap)?

Anticipation requires a single disclosure containing the full combination

For novelty (35 USC 102), anticipation requires one reference to disclose the method steps as claimed. The highest-risk anticipation path would be:

• a patent or publication that already teaches urine-based fetal sex testing using
  • a multi-analyte hormone panel,
  • antibody capture including hCG-beta,
  • and a redox indicator/FRAP-style measurement,
  • including calibration against known-gender standards.

In practice, many references cover only one or two clusters.

Obviousness is more feasible via an “element mosaic”

For obviousness (35 USC 103), a challenger can combine references:

• reference A: antibody immunoassays in urine/biofluids for estrogen/testosterone/progesterone/hCG-beta,
• reference B: redox indicator assays and FRAP/TPTZ chemistry in biological samples,
• reference C: sample aging/stabilization approaches that enable redox measurement in stored urine,
• reference D: diagnostic calibration to known outcomes.

Because claim 1 expresses a combination rather than a narrow reagent set, the legal fight typically becomes whether the combination would have been obvious to a skilled artisan with a reasonable expectation of success.

What formulation and delivery-system patents matter for this method patent?

Is there a “formulation” in the pharmaceutical sense

This patent is a method, not a drug formulation patent. The closest analogs to “formulation patents” are:

• redox indicator compositions,
• immobilization chemistries for antibodies on surfaces,
• and sample preparation reagent workflows.

Claim 1 is not limited to any single immobilization chemistry and instead focuses on functional components:

• “solid surface comprising antibodies specific to” each analyte,
• “redox indicator selected from” broad lists.

That broad functional language increases the probability that multiple prior art immunoassay surface preparations could be substituted unless the patent’s specification ties the claims to a specific immobilization approach.

What patent litigation risks exist for US 10,018,625 (Paragraph IV analogs don’t apply, but method infringement does)?

Paragraph IV is not the relevant framework

US method patents for diagnostics do not map to ANDA Paragraph IV events in the same way as drug product patents.

Risk profile for challengers

Infringement litigation would likely target one of three axes:

• non-infringement: challenger uses a different analyte panel, omits aging, uses different detection chemistry, or uses a different decision/calibration approach.
• invalidity: obviousness/anticipation based on combining hormone immunoassay art with redox assay art.
• claim construction: dispute over the meaning of “net redox activity” and whether the indicator change must be chemically specific vs broadly responsive.

What generic entry risks exist for competitors (how to design around claim 1)?

High-impact design-around levers

To reduce literal infringement risk, competitors can focus on:

1. Remove or change aging: use fresh urine or alter time/temperature beyond “at least about 2 days” ambient storage.
2. Change the antibody capture panel: omit one of estrogen/testosterone/progesterone/hCG-beta or replace with non-antibody capture.
3. Change the transduction: use direct electrochemical measurements without an indicator change tied to the enumerated indicator classes (though claim 15 keeps electrochemical in play).
4. Change decision framework: avoid “comparison with known net redox activity” standards in the way claimed.
5. Use different biomarkers or detection chemistry: switch to genomic or other biomarker approaches for fetal sex.

Because claim 1 is broad on indicator selection, a design-around that merely swaps the indicator family may still remain covered if the system still measures “net redox activity” via indicator property change and uses the antibody panel.

What is the FDA regulatory status of urine-based fetal sex testing using immunoassays and redox indicators?

Regulatory posture is likely device-led rather than drug-led

If commercialized, such a test would typically be evaluated under FDA medical device frameworks (in vitro diagnostics). The exact regulatory status depends on whether the company marketed it as an LDT or cleared device. No Orange Book listings apply to method patents.

Key takeaways

• US 10,018,625 claims a urine-aging + multi-hormone/hCG-beta antibody capture + redox-indicator readout + calibrated standard comparison method for fetal sex and ovum gender-specific compatibility.
• The patent’s enforceability centers on the specific combination in claim 1; dependent claims expand indicator, assay, and processing embodiments, raising the chance that substitutes still map to the claimed scope if they preserve the core workflow.
• The strongest invalidity attack is likely obviousness via combination across immunoassay and redox assay art; strict anticipation requires a rare single reference that discloses the whole integrated method.
• Competitive threats are primarily method-implementation risks: if competitors keep the aging and antibody panel while altering redox indicators only, they may still fall within scope.

FAQs

1. Can US 10,018,625 be infringed if only one of estrogen/testosterone/progesterone/hCG-beta antibodies is omitted?
   Claim 1 requires antibodies specific to all four analytes, so omission is a key non-infringement lever.

2. Does “electrochemical sensor” measurement avoid coverage of claim 1?
   No. Claim 15 expressly covers electrochemical measurement, so the design-around would need to avoid the claimed “net redox activity” detection structure rather than rely on sensing modality alone.

3. Is the “ambient temperature for at least about 2 days” aging step a likely infringement focus?
   Yes. Step-based requirements like this are straightforward to compare against competitor protocols.

4. Would switching from FRAP/TPTZ to a different redox chemistry automatically avoid infringement?
   Not necessarily. Claim 1 includes broad indicator categories, so avoidance depends on whether the substituted chemistry still constitutes “net redox activity” detected via indicator property change within the claimed framework.

5. Does this patent create exclusivity in the Orange Book sense?
   No. It is a method patent, and exclusivity analysis depends on patent enforcement and regulatory device status rather than Orange Book drug exclusivity.

References (APA)

1. United States Patent and Trademark Office. (n.d.). US Patent 10,018,625 (claims).

Details for Patent 10,018,625

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974		2034-06-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984		2034-06-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985		2034-06-23
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990		2034-06-23
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	March 26, 1974		2034-06-23