Patent Drafting – Biotechnology
Bellow is a letter you received from an inventor. Please use this as a basis for drafting a patent application. In case you feel that you do not have sufficient information for you to complete the specification you may include remarks and questions in the text requesting clarification or additional information from the Inventor.
The draft specification should be the basis of a fully-drafted application to be filed initially as a US provisional application. However, your client may want to file counterpart applications shortly, either a PCT application or straight filing (namely not through the PCT route) in the places that are most important to him – USA, Europe, Japan, Israel and possibly others. The client wants the specification already to be suitable for filing in all these important jurisdictions, to be able to file the applications in a very short notice. Thus, the drafting should be done in consideration of this fact. In particular, in case different claim formats are needed for different jurisdiction, all such claims should be included in the specification already at this stage.
It may help the client if you include a description on the claim strategy that you decided on.
When drafting, please disregard uniformity considerations; in other words the set of claims may include claims that may be regarded by examiners and patent offices to be directed to a number of different inventions.
BEHAZLACHA
The Inventors Letter
Dear Patent Attorney to be,
While I know that you are under pressure in view of your exams to become a patent attorney, the matter I will describe below could not wait until you are more at ease after finishing your written and oral exams.
I have been working on my research for the last 6 years and have had some breakthrough findings recently. I have been approached by a US-based multi-national pharmaceutical corporation that wants to enter into research collaboration with me and my academic lab in the Royal Academy of Southern Mitzpe Ramon. They are very anxious to begin to sign a collaborative agreement right away and hence the urgency. They learned of my work through an abstract that I presented in a scientific meeting that was organized by ISFS (the Israeli Society of Frustrated Scientists). The abstract is appended below.
I have been working for a number of years on the link between a certain blood factor – Factor FYI and the susceptibility to having cancer. The foundations of my work rest in a clinical observation that was made by my former teacher, Prof. Little, that individuals that have a relatively rare skin disease – Rareskinitis – get cancer only very rarely. His initial observations were published in the Journal of Non-credible Results in 1981 jointly with another scientist, Dr. Sense (Little & Sense, JNR, volume 7, pp 324-362, 1981). He then made a 12-year clinical study in which he observed 123 individuals age 50 and above with Rareskinitis and documented the diseases they got over the years, and compared it to a control group which were a mixed population of 142 individuals (also age 50 and above) that did not have this disease. His findings that were published shortly before his retirement in JPAPE (the Journal of Papers not Accepted for Publication Elsewhere) (Little et al, JPAPE J., Vol. 325, pp 987-996, 1998) showed the following (the table is reproduced from the manuscript):
Group / Gender / No. / Colon cancer / Lung cancer / Prostate cancer / Breast cancer / Others / TotalNo / % / No / % / No / % / No / % / No / % / No / %
Rareskinitis patients / Men / 69 / 2 / 2.9 / 0 / 0 / 2 / 2.9 / 2 / 2.9 / 6 / 8.7
Women / 54 / 1 / 1.9 / 2 / 3.7 / 2 / 3.7 / 2 / 3.7 / 7 / 13
Control group / Men / 68 / 6 / 8.8 / 7 / 10.3 / 5 / 7.4 / 5 / 7.4 / 23 / 33.8
Women / 74 / 4 / 5.4 / 6 / 8.1 / 4 / 5.4 / 4 / 5.4 / 18 / 24.3
So a total of 41 – 28.9% – out of the control group got cancer (the study was conducted in PollutionValley that has a high cancer incidence) while only 13 – 10.6% – of the Rareskinitis patients got cancer. The results were highly statistically significant.
These findings did not generate a big interest (after all, who reads the APAPE Journal?) but nonetheless one group in Australia and another one in Germany made some progress in the understanding of the relative immunity of the Rareskinitis patients to cancer. The Australian group found that the blood contains a factor that inhibits proliferation of cancer cells. They incubateed blood withdrawn from Rareskinitis patients together with cancer cells and showed that the cancer cells' proliferation was dramatically reduced.. In fact they noted that the cell cycle was arrested with the cells being blocked in the G0/G1 phase of the cell cycle (Garagmel et al, J. Unbelievable Results, Vol. 23, pp 1223-1242, 2000). The German group went a step further and managed to show that this factor, they termed "Factor FYI" is a soluble factor that has a molecular weight below 3,000 Dalton. They did it through filtration of the blood plasma through a 3000 Dalton cutoff membrane and found that most of the activity, determined through the ability to inhibit cell proliferation, filtered through such a membrane (Bobsfog et al, AND (Annals of Nonsense Data), Vol. 12, pp 2-21, 2001).
This was the background on which I began my research. Over the last 6 years I have accumulated a large body of data that allowed me to better understand the biological activity of Factor FYI, its nature, and understand its therapeutic potential. The results are described below.
1.Initial physicochemical and biological characterization of Factor FYI
Cell proliferation assays were used to test the effect of plasma from Rareskinitis patients (pooled plasma from 10 patients) as well as such plasma treated in a manner described below. The findings can briefly be summarized as follows:
-Plasma of Rareskinitis patients inhibits proliferation of cancer cells in vitro. Results can be seen in the attached Fig. 1.This effect is specific as there is no such effect on non-cancer cells, such as normal proliferating lymphocytes or fibroblasts.
-There was no effect on the proliferation inhibitory effect of the Rareskinitis patients' plasma after each of the following treatments: autoclaving and digestion with proteolytic enzymes. It could thus be concluded that Factor FYI is not a protein or a peptide and is heat stable.
-Ultrafiltration through a 1000 Dalton Amicon membrane was carried out and found that most of the anti-proliferative activity (about 90%) filtered through. This signifies that the Factor FYI has a molecular weight somewhat less than 1000 Dalton.
-The ultrafiltrate was passed through a lectin column (Infernion Type L) that captures sugar molecules or molecules with a sugar component. The anti-proliferative activity in the eluate was significantly reduced which is suggestive that Factor FYI is a sugar or a molecule with a sugar moiety.
Unfortunately, although I tried for a long time, my attempts to decipher the molecular structure of this Factor were so far unsuccessful.
2.Activity In Vivo
Oral administration of diluted plasma sample (1:100 dilution; 1 ml) to mice inoculated with tumor cells, gave rise to a marked reduction in the tumor proliferation in the animals. An exemplary result can be seen in the attached Fig. 2. I was very excited by these data as I was not entirely sure that Factor FYI would not be degraded in the gut or intestine.
I repeated such experiments many time in many tumor models and found activity across a broad range of solid tumor cells.
3.The receptor story
Notwithstanding the fact that I was unsuccessful in characterization of Factor FYI, I was able to demonstrate that it binds to a certain cell surface receptor by the name of Receptor X. Receptor X is a known receptor but up to now its function was not known. I managed to demonstrate that upon incubation of a blood plasma from Rareskinitis patients that contains Factor FYI, Receptor X induces a highly specific signaling pathway that eventually causes up-regulation of GSK-3β (which is down-regulated in tumor cells) and down-regulation of Cyclin-D1 and c-myc (both known for their involvement in the cancer process and are up-regulated in cancer cells).
I also used a certain monoclonal antibody that binds specifically to Receptor X and in the presence of this MAb, Factor FYI does not induce its tumor cells proliferation inhibitory effect and also does not induce the abovementioned signaling pathway modulation.
4.Additional molecules
We have purchased a compound library and begun screening for small molecules that will be able to affect the receptor in a manner similar to that of Factor FYI. We have found so far 2 such molecules, which look promising. I don't have the formulae of these molecules but will forward them to you shortly. You may refer to them for now as Compounds X107 and X187, which is their code in the compound library. However, I am not sure that these 2 molecules are the best we can find and I am confident that in the near future we will find some more. The X107 and X187 molecules
As I indicated there is a good likelihood that my laboratory will enter into a collaboration with a multi-national pharmaceutical company. The plan is to develop a drug for use in cancer treatment that will target Receptor X. The plan is to either fully characterize Factor FYI and use this as a basis for an anti-cancer drug; or use the synthetic approach and continue to look for suitable drug candidates in compound libraries.
Fig. 1: The effect of plasma from Rareskinitis patients in inhibiting proliferation of various types of murine or human tumor cell lines. Cells were incubated in a 96 well microtiter plate (1x105 cells/well) and plasma of Rareskinitis patients was added. Plasma from normal subjects serves as control. The results are shown a % of control.
Fig. 2: shows the tumor size, over time, developed in nude mice following injection of HCT-116 human colon carcinoma cells, in a control group and in a treated group (treatment was by oral administration.
Abstract Presented in the ISFS Meeting
Characterization of Anti-cancer Activity Found in the Plasma of Rareskinitis Patients
Background: Rareskinitis patients have a much lower incidence of cancer than the normal population (Little & Sense, 1981; Little et al, 1998). It was found that plasma of Rareskinitis patients contains a factor, termed Factor FYI that causes tumor cells to stop proliferating through a cell cycle arrest in the G0/G1 phase of the cell cycle (Garagmel et al, 2000). It was further found that the Factor FYI has a molecular weight below 3000 Dalton (Bobsfog et al, 2001). It was the object of our work to further study the Factor FYI and its biological effect. We have tested the capacity of pooled plasma from Rareskinitis to inhibit proliferation of cancer cells. Proliferating non-cancer cells were used as control.
Materials and methods: The cancer cells that were used included AX-12 lymphoma cells and BZ-117 colon cancer cells; non-cancer cells that served as control included BY-15 proliferating lymphocytes, lymphocytes freshly obtained from human blood donors (incubated with a mitogen to induce them to proliferate), and fibroblasts. The cells were seeded in a 96 well microtiter plate (1x105 cells/well). Pooled plasma from 10 Rareskinitis patients was filtered through a 3000 Dalton Amicon filter and diluted 1:100. 50 µl of this diluted filtered plasma was added to each well. Proliferation was assessed using the [3H]-thymidine incorporation assay. As an intrinsic control for each cell type, the proliferation of each type of cells was compared to the proliferation of cells of the same type incubated with 50 µl of similarly diluted and filtered plasma from normal blood donors (the proliferation of these cells was scored as 100%).
Results and discussion: The diluted and filtered plasma was effective to inhibit proliferation of the cancer cells, yielding for the AX-12 cell line 23% of control (namely 77% inhibition of proliferation) and for the BZ-117 31%. There was hardly any effect on proliferation of the non-cancer cells yielding the following results: 97%, 104% and 99%, as compared to control, for the BY-15 cells, fresh lymphocytes and fibroblast. These findings suggest that Factor FYI has a differential effect on tumor and non-tumor cells. This differential effect may be of importance in developing Factor FYI as a drug for the treatment of cancer with a specific effect and reduced side effects as compared to current treatment.