A 2025: lateral flow test - our provisional answer
Two DP-tutors (Nico and Nyske) sat paper A this year as benchmarkers. When comparing our answers, it turned out that we had largely the same solution, differing only in details of the wording.We both stuck closely to the wording of the paper, and incorporated some embodiments of D1 into our (dependent) claims. D1 turned out (again) to have some useful things in it.
A claim 1 according to our solution could read something like:
1. Lateral flow test, comprising:
- a sample pad (1) for receiving a liquid sample (5),
- a conjugate pad (2), which is arranged downstream of the sample pad (1),
the conjugate pad (2) containing a detection agent (11),
the detection agent being a conjugate (11) of a first type antibody (10) and a coloured particle (9),
wherein the first type antibody (10) is adapted to specifically recognise and bind to a target
molecule (6) in the liquid sample and wherein the coloured particle has a spherical shape,
- a reaction membrane (3), which is arranged downstream of the conjugate pad (2),
which
reaction membrane (3) comprises a test line (7),
the test line (7) comprising second types antibodies (12) that are specific for the target molecule (6)
and are immobilised in a line across the surface of the membrane,
characterised in that the coloured particle is a spherical gold nanoparticle having a diameter
of 20 - 100 nm.
As will be clear from a comparison with D1, the focus of the invention are the coloured particles. D1 does not explictly mention that it's spherical, however, according to par. [008] of the client's letter, the coloured particles must have a spherical shape to ensure they move at a consistent rate. Therefore, we assumed that the blue latex particle of D1 also would have to be spherical in order for the test of D1 to work.
D1 has a lot of features in common with the invention, but the final paragraphs [014] and [015] of the client's letter move away from the blue latex particles to replace them with gold nanoparticles. D2 mentions colloidal gold , which is a solvent with gold nanoparticles in it. However, the client's letter does not mention the solvent so there is no need to put the colloidal gold in the claim.
In par. [015], the clients letter says: "We have experimented with gold nanoparticles from other manufacturers and found that any type which has a diameter of 100 nm or less is suitable for our test, since larger particles do not have the necessary red colour." We learn from this that we don't need to limit the claim specifically to the nanoparticles of the manufacturer D2. The limitation of a diameter of 100nm or less appears to be necessary in order for the invention to work. Limiting to "the necessary red colour" seems to have risk of being unclear, because what is necessary"? Par. [014] mentions "intense ruby-red" but it will be hard and even subjective to determine which red would be "intense ruby-red" and which red would not be. Because the client's letter says "necessary red colour" however, we don't have a basis for extending the gold nanoparticles to any acolour. So, having an upper limit of 100nm diameter seems to make sense.
Similar considerations apply to the lower limit of the diameter of the gold nanoparticles. Paragraph [015] tells us that "We also found that gold nanoparticles with a diameter of less than 20 nm cannot carry sufficient antibodies to give an accurate result.". Apparently, the invention does not work with nanaparticles of a smaller size.
We both included at least one claim to a kit comprising the lateral flow test according to any one of claims .. and an extraction solution for suspending a test sample.
Also, we both had a claim to the combination of a plastic cassette and the lateral flow test (or test strip thereof), either in the form of a regular dependent claim or as a claim to the plastic cassette containing the test/test strip.
We did not see any use to include a use claim or a method for ex-vivo diagnostics. Such claims would not add any further scope of protection as the product is already claimed. In addition, there were more than enough embodiments for dependent claims.
We also both decided against a separate claim for the detection agent, as the technical effect seemed to be linked to the use in the lateral flow test.
For dependent claims, we saw for example the following options:
- gold particle 40 nm diameter
- control lime + associated features
- reaction membrane of nitrocellulose + optional pore sizes
- wicking pad
- the wicking pad (4) is made from cotton, cellulose filter or glass fibre
- first type antibody = second type antibody
- the conjugate pad (2) is made from non-woven glass fibre.
- the sample pad (1) made of cellulose fibre.
- the first antibody (10) has a binding affinity having an equilibrium dissociation constant equal to or less than 10 -7M.
- the first antibody (10) and the second antibodies (12) are specific for human chorionic gonadotropin.
- the first antibody (10) and the second antibodies (12) are specific for a spike protein of SARS-CoV-2 virus.
-the conjugate pad (2) stores the detection agent (11) in dried form.
- the plastic casette is labeled to indicate a position of the test line (7) and optionally a position of a control line
- the extraction solution is a buffered solution, such as phosphate buffered saline.
Curious to hear your thoughts!
I think the uniform in D2 was there as a link to par. [008] of the client's letter. Say as an extra indication that the particles of D2 are suitabel for use in the invention. I did not put "uniform" in the claim, as I thought that might be an unclear term. There's no definition given in the paper what "uniform" means in objective terms. The only thing we know is that D2 mentions less than 1 odd shape per 100 particles, and that that's considered to be "extremely uniform". And less than 1 odd shape per 100 particles seemed to be unnecessary limiting because of the "extremely" uniform. At least, these were my considerations when doing the paper, I'm also curious what the Exam Committe had in mind.
ReplyDeleteI think "uniform" in itself is a rather unclear term - I don't know where the boundary between uniform and non-uniform is. As for the drawings, they seem to be schematic, so don't read too much in them.
ReplyDeletei had the same question! Generally double penalisation is avoided, but i don’t know how much points they are going to give you in this cases. I read in the compendium that the dependent claims are considered in light with the independent claim that you made on a case-by-case basis.
ReplyDeletethe pad 1 is essential for absorbing the sample, otherwise the sample cannot be absorbed and the test doesn’t work
ReplyDeleteYes, I agree with ABC123, in real life, you would Never deduce from the picture of D1 to State that the particles have a spherical shape. So the spherical shape should be novel over D1. Since it is related with a technical effect, there is also some Space for reasoning inventiveness.
ReplyDeleteIs accuracy and sensitity the same technical effect? Why would you assume that? On the same note, why is 20 nm requirement is connected to the sensitivity? Sensitivity and accuracy aren't the same.
ReplyDeleteControl line was NOT essential. The invention was about improving sensitivity of the test by gold nanoparticles, not the indication that the test was done properly
ReplyDeleteJBH - Right, I'm so stupid. Of course a skill person is going to look at the figure of D1, see a circular particle, and deduce :" I must make this latex particle in the shape of a sharpie pen"
ReplyDeleteWhy do you find it so difficult to remain objective and respectful in technical discussions? The sarcasm is inappropriate.
DeleteI understood the upper limit of 100nm to be necessary. If you don't have it, then you claim a product where the particles are invisible (e.g. 250nm particles). The claim is therefore not enabled. We are not given any other limit of sizes, and 100nm is the largest that the client knows will work. If having larger particles was important to them, they should have experimented to find the absolute upper limit and told us in the letter to claim that.
ReplyDeleteAlso, the invention is about improving sensitivity of the test. This is achieved by the intense red colour of <100nm so that you need fewer brighter particles to attach to the test line to see a positive line. If you provide blue of black particles, will you still be able to see the test line clearly with fewer virus/target molecules? I don't think so.
Finally, this isn't real life where you need to ensure your client gets the best possible protection on filing, and then narrow and divide in prosecution. You want to get novel and inventive claims based on the information you are given (but reasonably broad).
Anonymous from March 17, 2025 10:50 pm:
DeleteYou are contradicating yourself, I am afraid. You say:
"If having larger particles was important to them, they should have experimented to find the absolute upper limit and told us in the letter to claim that."
If the Client has not experimented and found the absolute upper limit and has no told you that clearly and unambiguously, why did you include in your claim? Why do you consider red colour to be superior to blue colour? Personal preference? :-)
Anonymous from March 17 10:50 pm: The broadest possible protection is not to assume what the Client provides as the correct information. You should apply the broadest possible protection under exam conditions. There are broad hints at paragraph 015 of the Client's letter to stay away from 100 nm limit. For instance, the wording "other manufacturers" i.e., not covering GoldiLocks as well as the wording "any type" i.e., not restricted to spherical shape give away the intention that "suitable" outweighs the "necessary" red colour in the same sentence.
ReplyDeleteAnonym saying "Finally, this isn't real life where you need to ensure your client gets the best possible protection on filing.."
ReplyDeleteHere is Rule 10 (4)(b) of IPREE of 2019:
"Candidates will be expected to answer questions on the allowability of the claim(s) under the European Patent Convention (hereinafter "the EPC") and as to whether the claim(s) provide(s) the broadest possible protection under the EPC. When answering the questions, candidates shall bear in mind the requirements of the EPC, in particular regarding novelty and inventive step, and the recommendations contained in
the Guidelines for Examination in the EPO (hereinafter "the Guidelines")."
It does not say the "best possible protection", but the broadest possible protection satisfying, in particular, the novelty and inventive step. Here is the case law book excerpt:
"The essential features should in particular comprise those which distinguish the invention from the prior art (T 1055/92, OJ 1995, 214; T 813/03). Regarding the delimitation of essential from non-essential features, see also T 61/94, T 203/98, T 141/00, T 260/01, T 1573/12, T 2131/12, T 21/16." (see https://www.epo.org/en/legal/case-law/2022/clr_ii_a_3_2.html)
What you're saying is, include another limitation of 100 nm because the client says so. It does not work that way.
You’re right in considering 100nm limit. Since there is no conclusive evidence to determine that diameter beyond which it is colorless, I have to rely on the recent G decision G 0002/21. I don’t think deltapatents took it into consideration. Here is g2/21 Headline:
Delete„
I. Evidence submitted by a patent applicant or proprietor to prove a technical effect relied upon for acknowledgement of inventive step of the claimed subject-matter may not be disregarded solely on the ground that such evidence, on which the effect rests, had not been public before the filing date of the patent in suit and was filed after that date.
II. A patent applicant or proprietor may rely upon a technical effect for inventive step if the skilled person, having the common general knowledge in mind, and based on the application as originally filed, would derive said effect as being encompassed by the technical teaching and embodied by the same originally disclosed invention.“
This means 100 nm isn’t relevant for the inventive step in view of G2/21. Just for the lack of conclusive experimental data, it’s wrong to include 100 nm in the claim which violates the recent case law of the enlarged board.
I agree with ABC123. The spherical shape should be enough for novelty over D1. The figure of D1 can‘t be enough for the disclosure of spherical particles.
ReplyDeleteThe Exam looked nice this time with the right balance between chemical and mechanical subject matter.
ReplyDeleteI did not put that the reaction membrane us arranged downstream of the conjugate pad (2) since I could not find the sentence in the text (and did not want to be creative). Further instead of using "the target molecule" I used in claim 1 "a target molecule" twice. Any idea of how many points this could cost?
ReplyDeleteI disagree with you. The role of gold in the conjugate is just to act as a visible reporter. The improved sensitivity is due to the vibrant red color. Nothing in D2 suggests that other color are as vivid and would achieve the desired increased sensitivity.
ReplyDeleteAdditionally D2 already promts the person to use gold particles in the conjugate, so for inventive step you have to restrict the claim to the aspect for which you can support
You need to check the selection inventions part of the Guidelines. Conjugating the gold nanoparticles with the antibody involves two selections!
DeleteUh? The client letter explicitly said that the sample pad was really important, due to its main function of redistributing the liquid evenly, etc.
ReplyDeleteHi everyone, I have started a PETITION to urge the EPO to offer the EQE twice a year, thereby minimizing the negative psychological impact on our mental health when we fail one part of the exam (and thereby the whole exam! hence forced to wait one complete year to retake - as if lifetime is endless).
ReplyDeletePlease I urge you to sign the reasonable (vernünftig, raisonnable) petition and to share it with colleagues, friends, trainees, and whoever you think can accelerate taking a decision by the EPO.
Thank you DeltaPatents for allowing us to share our concerns about the exam. While many companies in this domain are very much profit and business focused, you are humain and quality focused. Thanks from the heart.
Petition:
https://chng.it/V29hwhJQ8n
I included the reaction zone. I did not include the test line in claim 1 since it is an implicit feature known to always exist in the reaction zones of lateral flow tests (LFTs) since the early fifties (Lateral flow test - Wikipedia). The test line is a well-established and common component in reactions zones of lateral flow assay devices and tests, which are widely used in diagnostics (i dealt with LTF for some time now). This is part of the common general knowledge for a person skilled in the art of lateral flow technology. Not including the test line in claim 1 is clearly allowable in this case, as asserted by the Guidelines GL F-IV 4.5.4: “As detailed above, an independent claim must specify explicitly all of the essential features needed to define the invention. This applies except in so far as such features are implied by the generic terms used, e.g. a claim to a "bicycle" does not need to mention the presence of wheels”.
ReplyDeleteThe technical effect of the invention (i.e., improved uniform flow rate and constant movement leading to improved binding efficiency and test sensitivity ) does not depend on the explicit mention of the test line. The test line is a standard feature in lateral flow tests and does not influence the core function of the invention, which is the use of spherical gold nanoparticles for detecting the target molecule (e.g., the viral spike protein in the case of a COVID-19 test).
I also did not specify any range either (not 20 to 100 and not above 20) for the gold nanoparticles, since it is not “clearly and unambiguously” stated in the client letter that this is needed to generate a technical effect that enables an inventive step. My arguments:
The client letter states: “We have experimented with gold nanoparticles from other manufacturers and found that any type which has a diameter of 100 nm or less is suitable for our test, since larger particles do not have the necessary red colour”.
This text means that larger particles do not have the necessary red colour. It does not say that larger particles (i.e. > 100 nm) do not improve the sensitivity or do not fulfill the increased detectability function. That only say that larger particles do have the red colour.
This sentence does not provide evidence that the test would fail for these larger sizes.
Furthermore, according to D2, LSPR results in a color shift depending on the size of the gold nanoparticle, with red colors appearing for spherical particles under 100 nm and a transition to blues, blacks, or clear/colourless for larger particles. The fact that larger particles do not produce the red color but still function in applications (even leading to color shifts) supports the notion that larger nanoparticles can still be used effectively in the invention, but with a different color. While the red color might be preferred for its visibility, the detection function itself (based on LSPR) is still valid, even with a different color. Thus, the technical effects of the spherical gold nanoparticles, namely the uniform flow rate, consistent movement, and hence improved binding efficiency and detection sensitivity still occur, just with a color variation, which does not invalidate the invention.
I also looked at the French version during the exam. There, it is even more clear that the limit >100nm is not needed: “Nous avons réalisé des expériences avec des nanoparticules d'or d'autres fabricants et découvert que tout type ayant un diamètre inférieur ou égal à 100 nm est adapté à notre test, les particules plus larges n'ayant pas nécessairement la couleur rouge nécessaire”. "N'ayant pas nécessairement" (par exemple dans "n'ayant pas nécessairement besoin de" ou "n'ayant pas nécessairement raison") indique que quelque chose n'est pas obligatoire ou évident, mais il y a une nuance qui suggère que ce n'est pas systématique. Cela introduit une idée de possibilité, sans certitude.
I also did not inlcude the test line, or that the antibodies in the reaction zone are immobilised in a line across the surface of the membrane. This is because this feature is implicit for the person skilled in the art of lateral flow "tests". This is an established test since the early 90s as known by the skilled person, and as also clearly indicated by the state of the art document D1: "The major breakthrough came in the 1990s with the development of lateral flow tests .... Since the 1990s, lateral flow tests have been developed for many different applications". I think that the Exam Committee knows that. But just in case, here are few granted European patents that do not mention in claim 1 (or in any claim) the test line or that the antibodies are "immobilised" in a line. You can use them to support your appeal if needed: EP2643696B1, EP3382395B1, EP3421995B1, ...
DeleteNow, let us talk about the second range limit (> 20 nm). The client letter says: “We also found that gold nanoparticles with a diameter of less than 20 nm cannot carry sufficient antibodies to give an accurate result”.
ReplyDeleteThis sentence clearly says that particles having a diameter of less than 20nm do not give accurate result, i.e. give inaccurate results. It does not say that said particles do not give any result at all or that said particles do not carry any antibodies at all, or that the detection fails, or that said nanoparticles cannot produce a detectable signal, or that the technical effect due to sphericity, namely the uniform flow rate and consistent movement does not exist anymore.
According to Webster, the term not accurate or innacurature means: “Inaccurate (adj.) as in approximate not precisely correct. Example: the estimate is inaccurate, but will do for our purposes”. This is what I understood from this client sentence: diameter below 20nm generates inaccurate results, but will do for our test purpose, i.e. will still provide the technical effects of uniform flow rate and consistent movement, and hence improved sensitivity, even if not to the fullest extent.
The primary role of the gold nanoparticles is to provide a visible signal and ensure uniform flow rate due to their spherical shape. The spherical shape of the gold nanoparticles ensures a uniform flow rate, which is essential for the consistent movement and binding efficiency in the capillary flow. This uniformity is critical for the overall performance of the lateral flow test, regardless of the nanoparticle size. Even if nanoparticles smaller than 20 nm carry fewer antibodies, the antibodies carried by these gold nanoparticles can still bind to the target molecule. The reduced antibody load may lead to weaker signals, but the binding and detection functions remain intact.
Conclusion:
The client letter does not clearly and unambiguously state that restricting the size to above 20 nm is necessary. It only highlights that smaller nanoparticles may not provide the highest level of accuracy.
The technical effect of the invention—improved uniform flow rate and constant movement leading to improved sensitivity and detection of the target molecule—is achieved by the use of spherical gold nanoparticles, which ensure uniform flow rate and consistent results, regardless of their size.
Thank you for your comments on this.
Ralf, I agree with all your arguments. I happened to work in the LFT field for some time now.
ReplyDeleteThe thing that is missing from your argumentation is the simple fact that the experiments and ranges (20 nm to 100 nm) are specific and valid only for the COVID target molecules experimented upon in the client letter.
If the customer is asking in its letter to protect the LFT "for COVID-19 along with other possible uses", the range 20 to 100 or any other range should not be included in claim 1 at all! This is exactly what fit to Practice means...
Lea - You might be onto something really critical here. I went back to paper A text again. Here is what the client is saying about "their test":
Delete"In our test, the target molecule being detected is the spike protein from the SARS-CoV-2 virus." paragraph 004
"The antibody must be able to specifically recognise and bind to the target molecule (6) in the liquid sample, which in our test is the spike protein produced by the virus." paragraph 007
"This means that it is possible to show results even when the concentration of spike protein (target molecule) is very low in the sample. We have experimented with gold nanoparticles from other manufacturers and found that any type which has a diameter of 100 nm or less is suitable for our test, since larger particles do not have the necessary red colour." paragraph 015
All these three paragraphs indeed refer to "spike protein" related at least to a virus, preferably COVID-19.
And I read this in conjunction with the following statements from paragraphs 001 and 002:
"However, as the number of COVID-19 cases has declined, the demand for these tests has decreased and so we are looking into other markets for our products."
"We would like to protect the latest developments of our technology with a new patent application that covers testing for COVID-19 along with other possible uses."
And voila! The answer pops, 100 nm upper limit was indeed not an essential feature. What a mischievous attempt at hiding their true intention.
Results? reports?
ReplyDelete