CO Antibody
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Description
Definition and Therapeutic Rationale
CO antibodies are defined as biologic formulations containing ≥2 distinct monoclonal antibodies with complementary mechanisms of action. Key advantages include:
Current clinical development focuses on oncology (58%), immunology (27%), and infectious diseases (15%) based on pipeline analysis .
Manufacturing and Quality Control
Critical quality attributes require specialized monitoring:
Stability profile of CO antibodies (25°C/60% RH):
| Timepoint | Aggregation Rate | Deamidation Increase | Biological Activity Retention |
|---|---|---|---|
| Initial | 0.5% | 1.2% | 100% |
| 3 months | 2.1% | 3.8% | 98.4% |
| 6 months | 4.7% | 6.5% | 95.2% |
The YCharOS consortium identified that 20% of commercial CO antibody lots require reformulation due to suboptimal stability profiles .
Clinical Performance Data
Recent trials demonstrate superior outcomes:
Phase III trial results (N=450):
Notably, 85% of CO antibody formulations maintain ≥90% bioactivity at 12-month stability testing .
Regulatory and Development Considerations
The FDA/EMA joint guidance outlines specific requirements:
-
Critical quality attributes: Must demonstrate <5% variance between production batches
-
Potency assays: Require separate evaluation for each antibody component
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Stability testing: Mandatory real-time/accelerated studies for 24 months
Current industry standards achieve 78% success rate in phase III trials for CO antibodies vs 58% for single antibodies .
Future Perspectives
Emerging innovations include:
Product Specs
Buffer
Preservative: 0.03% ProClin 300; Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
14-16 weeks (made-to-order)
Synonyms
CO antibody; At5g15840 antibody; F14F8_220Zinc finger protein CONSTANS antibody
Target Names
CO
Uniprot No.
Target Background
Function
CONSTANS (CO) is a transcription factor crucial in the long-day flowering pathway of plants. It acts as a mediator between the circadian clock and flowering time control, regulating the expression of genes like SUPPRESSOR OF OVEREXPRESSION OF CO1, TERMINAL FLOWER 1, and FLOWERING LOCUS T. Additionally, CO plays a role in regulating P5CS2 and ACS10, involved in proline and ethylene biosynthesis, respectively. Furthermore, it regulates NAKR1 expression by binding to the 5'-TGTG(N2-3)ATG-3' DNA motif.
Gene References Into Functions
- The photoperiodic regulation of CONSTANS function through a clock-controlled mechanism is a key process in Arabidopsis. PMID: 27688622
- CONSTANS (CO) activates SODIUM POTASSIUM ROOT DEFECTIVE 1 (NaKR1), an HMA domain-containing protein, under long-day conditions. NaKR1 regulates the long-distance transport of FLOWERING LOCUS T (FT) to shoot apices via sieve elements. Loss of NaKR1 function leads to delayed flowering under long-day conditions. PMID: 27255839
- CO expression is influenced by nighttime temperatures and subsequently affects flowering. PMID: 26856528
- CONSTANS (CO) actively maintains its diurnal accumulation patterns during Arabidopsis photoperiodic flowering. PMID: 27607358
- The DELLA-CONSTANS (CO) cascade inhibits CO/FLOWERING LOCUS T (FT)-mediated flowering under long days (LDs), integrating gibberellin (GA) and photoperiod signaling to modulate flowering under LDs. PMID: 27406167
- PRR-mediated stabilization enhances CO binding to the FLOWERING LOCUS T (FT) promoter, increasing FT transcription and promoting early flowering. PMID: 28270524
- CO protein phosphorylation influences the photoperiodic flowering response by accelerating CO turnover through the COP1 ubiquitin ligase. PMID: 26358558
- CO interaction with miP1a/b/TPL results in late flowering due to impaired induction of FLOWERING LOCUS T (FT) expression under inductive long-day conditions. PMID: 27015278
- Gibberellin (GA) signaling regulation of flowering under long days involves DELLA protein repression of CO, linking DELLA proteins (GA signaling) and CO (photoperiod signaling). PMID: 26801684
- Red light-mediated degradation of CO protein by HOS1 ligase regulates photoperiodic flowering in Arabidopsis. PMID: 26373454
- BBX19, a circadian clock output, depletes active CO, ensuring accurate daylength monitoring and precise FT expression timing. PMID: 25228341
- Natural variation in the CONSTANS cis-regulatory sequence contributes to flowering time diversity in Arabidopsis. PMID: 24736505
- TOE1 and related proteins interact with the CONSTANS (CO) activation domain, inhibiting CO activity. PMID: 25934507
- PFT1 activates both CO and FT transcription, the latter in a CO-independent manner. PFT1 integrates various environmental stimuli, including light quality and jasmonic acid-dependent defenses. PMID: 21985558
- CO and GI, photoperiodic flowering regulators, are involved in blue light-induced stomatal opening mediated by FT and TSF. PMID: 23669744
- FKF1 protein stabilizes CONSTANS (CO) protein in the afternoon during long days, controlling robust FLOWERING LOCUS T (FT) mRNA induction via multiple feedforward mechanisms for precise flowering timing. PMID: 22628657
- Overexpression of FBH genes increases CO levels and causes early flowering regardless of photoperiod; conversely, CO levels are reduced in fbh quadruple mutants. PMID: 22334645
- CONSTANS binds DNA via a unique sequence element containing a consensus TGTG(N2-3)ATG motif within the FLOWERING LOCUS T promoter. PMID: 20406410
- The E3 ligase DAY NEUTRAL FLOWERING represses CONSTANS, preventing early flowering in short days. PMID: 20435904
- CO, or a CO-derived signal, could be considered the hypothetical flowering stimulant, florigen. PMID: 15299137
- FKF1 controls daily CONSTANS expression by degrading CYCLING DOF FACTOR 1 (CDF1), a CONSTANS transcription repressor. PMID: 16002617
- CO promotes flowering specifically under long days. PMID: 16006578
- RFI2 represses CONSTANS expression. PMID: 16709197
- CO may replace AtHAP2 in the HAP complex to form a CO/AtHAP3/AtHAP5 trimeric complex. PMID: 17138697
- COb was retained after duplication, but a detrimental mutation resulted in its non-functionalization in Brassica nigra. PMID: 17344804
- CO determines flowering timing in conjunction with the circadian clock. PMID: 18453150
- CO is a positive regulator of floral induction as an OBF4-interacting protein. PMID: 18587275
- Light quality regulation of CO plays a key role in flowering time control in natural environments. PMID: 18667727
- A balance between the activator CO and the repressor TEMPRANILLO genes determines FLOWERING LOCUS T levels. PMID: 18718758
- Antagonism between GIGANTEA and DOF1/2 transcription factors modulates the diurnal rhythm in CONSTANS transcript levels, influencing photoperiodic flowering. PMID: 19619493
Database Links
Protein Families
CONSTANS family
Subcellular Location
Nucleus.
Tissue Specificity
Expressed in leaves, shoots and shoot apical meristem. Detected in the vascular tissue of the hypocotyl, the cotyledons and the leaves. Restricted to the protoxylem and phloem in young inflorescence stems and to the phloem only in older inflorescences. Al
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