“Proof of Concept” Rabbit Experiments Demonstrating GHR106 (hIgG4) as GnRH Antagonist
Bibliographic record
Abstract
“Proof of Concept” (P-o-C) experiments in rabbits were conducted to demonstrate reversible suppressions of serum reproductive hormones (LH, testosterone or E2) upon a single injection of a humanized monoclonal antibody against human GnRH receptor, GHR106 (hIgG4). In the case of a male rabbit, a single subcutaneous injection of either 1 mg/kg or 3 mg/kg of the antibody was shown to reduce concurrently the serum LH and testosterone concentrations by 60 to 80% for a period of one week or longer. The reproductive hormone levels returned to the normal range after next two weeks. Similarly, the suppressions of LH and estradiol (E2) were also observed within two days upon a single injection of GHR106 (hIgG4) in the female. The E2 levels can decrease to 30-60% of the normal over a period of one week followed by full recovery of both hormones during the next 5-10 days. P-o-C experiments were expanded to a scale of more than 30 rabbits with identical protocols to those of a single rabbit, in addition to the comparisons with those of the negative control. Reversible suppressions of reproductive hormones were observed consistently with all rabbits in the antibody injection groups, and were shown to be statistically significant. The circulation half-life of GHR106 (hIgG4) in rabbits was estimated to be 4 ± 1 day. Therefore, the results of this study revealed that GHR106(hIgG4) can be used as antibody-based long- acting GnRH antagonist with similar biological actions to those of decapeptide GnRH antagonist such as Cetrorelix or Antide. The relatively long half-life of the antibody-based GnRH antagonist, however, may be more beneficial to the treatment of gynecological and fertility-related diseases which may be caused by modulations of human GnRH receptor in humans, and also in other animal species for fertility controls.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".