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Well not quite "sparing normal health tissue" (sic)... "having minimal effect on normal healthy tissue" would be more precise.

(...continued)

In one embodiment, the target small molecule is cortisol, vitamin B12, estradiol, testosterone, or 25-hydroxyvitamin D2 and/or D3.

In one embodiment, the second binding polypeptide is an antibody or fragment thereof (e.g. a monoclonal antibody or fragment thereof) or a naturally occurring polypeptide.

In one embodiment, the target small molecule is cortisol, estradiol, testosterone, or 25-hydroxyvitamin D2 and/or D3 and the second binding polypeptide is an antibody or fragment thereof (e.g. a monoclonal antibody or fragment thereof).

In one embodiment, the target small molecule is vitamin B12 and the second binding polypeptide is transcobalamin II, and the complex is holotranscobalamin.

In one embodiment, the recombinant first binding polypeptide comprises an amino acid sequence represented in formula (I):

NTB-HP1-CB-HP2-CTB"

(...continued)

Further obstacles arise when attempting to detect and/or quantify a target small molecule in a so-called ‘sandwich’ format. Most binders in such a complex will effectively cover all available epitopes on the target small molecule. Therefore, most assays rely on competition between the two binders for binding to the small molecule. That results in an indirect readout. In such assays, the readout depends on a decrease in signal that correlates with an increase in target analyte. However, such indirect readouts resulting from competitive binding of two binders to the same target analyte are inherently less specific and/or less sensitive. Importantly, a direct readout also provides a broader dynamic range and/or a reduced susceptibility to cross-reactive binding.

There is a need in the art for approaches to detect and/or quantify target small molecules by assays that produce a direct positive readout, i.e., in which an increase in signal directly correlates with an increase in target analyte.

SUMMARY OF THE INVENTION

The present invention provides recombinant (first) binding polypeptides (e.g., Affimer® polypeptides) and methods of using them to detect small molecule analytes in biological samples with high specificity and sensitivity. The recombinant first binding polypeptides of the invention bind specifically to a complex of a target small molecule with a different (second) binding polypeptide (e.g. an antibody or a naturally occurring binding protein) and, in doing so, can be used to specifically detect the target small molecule. Recombinant first binding polypeptides of the invention are capable of specifically detecting target small molecules with high sensitivity and specificity, including target small molecules having a molecular weight of 2 kDa or less.

Thus, the present invention provides reagents, means and methods for detecting a target small molecule (including those with molecular weights of 2 kDa or less) that avoid detection of cross-reactive, structurally similar non-target small molecules and/or that avoid detection of the second binding polypeptide not specifically bound to the target small molecule.

In one aspect, the present invention provides a recombinant first binding polypeptide that specifically binds to a complex of a second binding polypeptide and a target small molecule,

wherein the recombinant first binding polypeptide is a recombinantly engineered variant of cystatin polypeptide,

wherein the second binding polypeptide binds specifically to the target small molecule, and

wherein the target small molecule has a molecular weight of 2 kDa or less, optionally wherein the target small molecule is a steroid, an organic compound, a hormone, a hapten, a vitamin, a biogenic amine, an antibiotic, a mycotoxin, a cyanotoxin, a nitro compound, a nucleotide or an amino acid.

(continued...)

About the invention. There are two big clues that this patent is not relevant to Avacta's current activities. Firstly, Matt Johnson was in the Diagnostics division and secondly, the inventors' location is given as Wetherby, not Scale Space.

The title of the patent - POLYPEPTIDES AND METHODS FOR DETECTING AND QUANTIFYING SMALL MOLECULES - is a hint that this is about diagnostics, a hint which is confirmed in the Description section for the invention ( https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025191078&_cid=P10-MFPANN-29543-1 ) as there is no mention of doxorubicin, FAP, fibro, cancer or oncology:

"BACKGROUND TO THE INVENTION

Continuous monitoring of small molecule (analyte) levels in biological samples from individuals continues to be of increasing importance, e.g., in assessing and treating metabolic and medical conditions.

For many small molecule analytes, it is important to be able to assess and monitor their levels reliably with high specificity and sensitivity, to draw conclusions about underlying medical conditions or metabolic statuses. This can be a particular challenge for small molecules having a molecular weight of, e.g., 2 kDa or less, 1.5 kDa or less, or 1 kDa or less.

Additional problems and technical challenges can arise from the fact that, in addition to a target small molecule, a typical specimen may contain further compounds that are structurally highly similar to the target small molecule. These may be, e.g., metabolites of a target small molecule, drug compounds that are very closely related to a native target small molecule, or closely related compounds of the same class as a target small molecule. Due to the low molecular weight of certain target small molecules (analytes) of interest, it can be difficult to detect and/or quantify the target small molecule without simultaneous background readout from such distinct, but structurally highly similar, non-target compounds. It is desirable that, in an assay for detecting and/or quantifying a target small molecule, the cross-reactivity of the detection agents to structurally similar non-target small molecules be reduced, minimized, and/or avoided as far as possible, including cross-reactivity to non-target small molecules with very high degree of structural similarity. For example, antibodies that target cortisol can cross-react to a certain extent also with prednisolone. This results in readouts that do not correctly represent the physiological situation in vivo, and thus hinder meaningful and effective detection, diagnosis and/or treatment.

Thus, there is a need in the art for novel approaches to detect and/or quantify small molecule analytes with high sensitivity and specificity, avoiding cross-reaction of the detection reagent(s) with closely related small molecule compounds of a similar structure.

(continued...)

OK some facts about this WO patent, the most pertinent to us being the timings.

The first patent application was GB2403780.6, filed on 15 March 2024 ( https://www.search-for-intellectual-property.service.gov.uk/GB2403780.6 ). That is the priority date for the patent family (the family of patent applications around the world for this invention). The GB patent application was abandoned as is normal when EP (covering Europe) and/or WO (covering the world) patents are filed within the one year time limit for claiming that priority date.

The WO patent, WO2025191078, was filed on 13 March 2025 and covers, inter alia, GB amongst the 'Designated States' ( https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025191078&_cid=P10-MFPANN-29543-1 ). This WO patent was published on 18 September 2025.

So the timings from the first application are up to one year to file the invention around the world claiming the priority date, and then about six months for the WO patent to be put into the public domain. Thus, if the AVA6103 patent application was filed - likely as a GB patent - in September 2024, we can expect it to be filed around the world in September 2025 with the first publication in March 2026. Avacta are extremely unlikely to disclose the structure of AVA6103 before then as they'll want to keep their commercial secrets secret for as long as possible and they certainly won't disclose to anyone before all the patents claiming that September 2024 priority have been filed as such 'prior disclosure' would then bar them from filing any more patent applications.

You know the old saying: garbage in, garbage out.

Dr Tap is NOT going to be there just for Avacta

Dr Tap is going to be there just for Avacta, so who pays for his attendance is moot. He'll also be doing these:

Friday, 17th: Young Oncologists session: The biggest twists in my career

Speakers: Jarushka Naidoo (Dublin, Ireland) Carmen Criscitiello (Milan, Italy) William D. Tap (New York, United States of America, NY) Petros Grivas (Seattle, United States of America)

Lecture Time: 14:00 - 15:00

Monday, 20th: Special symposium: Therapeutic innovation to improve outcome in sarcomas (08:30 - 10:00)

Biology to guide development of new therapies (08:30 - 08:45)

Speaker: William D. Tap (New York, United States of America, NY)

and possibly

Tuesday, 21st: Scientific Congress Highlights 2 (09:00 - 12:40)

Sarcoma (09:20 - 09:40)

The pub bore trader wrote: "BV you are as bad as any other for dismissing an opinion or "critical thought" you don't agree with a childish insult."

No, it doesn't work like that. You are a bad actor who changes your view according to whether you are in or out and tries to manipulate accordingly. You have no integrity and thus no credibility. You add nothing of value concerning the science so can be safely ignored on that aspect.

More failings than just the Diagnostics paragraph on the Key Information page.

The Corporate Governance page is what it is if it is only updated once a year after the Annual Report & Accounts is published as I guess it has to align with that printed document. They could have included addenda at the end though if they wanted to have an up-to-date record.

I've just pointed Karen Harrison to the Avacta profile in Investor Meet Company.

"Avacta Group Plc develops cancer therapies and diagnostics in the United Kingdom, France, North America, South Korea, and rest of Asia and Europe. The company operates through Diagnostics and Therapeutics segments. It develops products based on its proprietary Affimer and pre|CISION technology platforms. The company develops AVA6000, FAPa-activated doxorubicin that is in Phase I clinical trial for treating locally advanced or metastatic-selected solid tumors; AVA3996, a tumor-targeted proteasome inhibitor based on bortezomib; AVA-028-PD-L1 Affimer/ImmunoCytokines; AVA-021 - PD-L1 Affimer/LAG-3 Affimer; and TMAC platform that utilizes the proprietary pre|CISION substrate to provide for the selective release of a drug moiety by FAPa. The company has a collaboration agreement with LG Chem for developing and commercializing LR19128 PD-L1 XT; and collaboration and license agreement with Avacta and Daewoong Pharmaceutical Co. Ltd. for developing AFX-001 for solid organ transplant and graft vs host Disease, and AFX-002 for multiple sclerosis. Avacta Group Plc was incorporated in 2003 and is based in Wetherby, the United Kingdom."

Let's see what happens.

Company mission statements, value statements, etc. are just irrelevent marketting blurb. No business ever said "We try sometimes to provide a good service if our staff aren't overworked" and the 'fact' that there are "dedicated experts available to satisfy your individual needs" should be expected but read as the former. Well at least that's my experience at Barabara's Hot House.

Sure, I realise CC is busy and doesn't want to get involved at the operational level, but how long does it take to forward an email with a "Please look into this" message added? When the company's image is at stake...

Bella wrote "It was another Vinegard error...having exchanged Emails on 30 July with Jack at ICR & CC pointing out the mistake it has now been corrected in todays RNS"

I also emailed CC about this on 30 July but she doesn't seem to pass actions on* as the italicised note had not been added to the announcement page https://web.archive.org/web/20250804212726/https://avacta.com/avacta-to-present-new-fap-dox-ava6000-data-at-the-european-society-for-medical-oncology-esmo-congress/ by 4 August and may not have been added until very recently, possibly not until Karen Harrison took over responsibility for communications. I think she is the one to contact, even though an inhouse contact name has now been removed from RNS's.

*Informing CC that 'AVA7103' was an obvious mistake produced no correction. Informing KH got it corrected within an hour or two.

The ESMO poster presentation date time and location has not changed, and is as it was when Avacta put out the original notification.

I'm getting a handhold on CC's character. This is the fourth time that I know of where she has smothered the truth to make Avacta look good.

People have to take responsibility for their investments. If they hear that company X's share price is exploding and they rush over to buy only to get spiked, then that's their lookout. Chasing rainbows may be fun but you're likely to get soaked.

A mistype, I think. Actually meant 2015 and he's now 66.

What a strange person. Seems obsessed with his piles. Very odd.

Not just a Novartis branded rucksack, a Novartis branded laptop rucksack - gotta ping headquarters ASAP with photos of the poster.

The 'investor event' after the poster presentation will be like every investor event after a poster presentation. It will be an explanation of what was presented in the poster. No reason to get excited about it as being anything special other than what is in the presentation - and we will get the poster abstract about what is in the presentation before the actual presentation.