Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Summary
This is the Non-Final Office Action based on application 18/128260 filed 03/30/2023.
Claims 1-18 have been examined and fully considered.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in United States at the USPTO on 03/30/2023. It is noted, however, that applicant has not filed a certified copy of the IL277743 application as required by 37 CFR 1.55.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1-18 are directed to non-statutory subject matter.
Through 101, inquiry analysis:
Are the claims directed to a statutory category of invention?
Yes, independent claims 1, 8, & 14 are drawn towards a statutory category method.
Do the claims involve a Judicial Exception?
Yes. Claims 1 & 8 involve the judicial exception of diagnosis of breast cancer based on detection of levels of the claimed biomarkers. This is a natural correlation. Further, comparison to a threshold or reference is simple math or a mental process which is an abstract idea.
For Claim 14, it involves a product of nature judicial exception, since all that is required for the claimed kit is antibodies, and these are products of nature.
Analysis of other factors to determine if the claim qualifies as eligible and ismore than the natural correlation/abstract idea.
Step 2A/2-Do the claims practically apply the judicial exception?
For Claims 1 & 8, there are no features instantly claimed which practically apply the judicial exception.
Claims 1 & 8 both require treatment steps, however all that is claimed is a “therapeutic agent,” “directed against breast cancer cells.”
This treatment does not read as particular or specific. First of all, the claim still reads as conditional in that a treatment is not always performed in the boundaries of the claim since the treatment is only performed, “upon confirmation”. Therefore- there is not always required to be a practical application.
Further—the claimed treatment of a “therapeutic agent,” “directed against breast cancer cells,” is akin to “administering a suitable antibiotic.” Though this is slightly more specific--- the MPEP points out that “administering a suitable medication,” is not particular and specific treatment. See MPEP 2106.04 (d)(2):
“Consider a claim that recites the same abstract idea and “administering a suitable medication to a patient.” This administration step is not particular, and is instead merely instructions to “apply” the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.”
Therefore- this treatment is not particular or specific as claimed and therefore do not practically apply the claimed judicial exceptions. Also, see Vanda Memorandum.
Claims 1 & 8 also require, “isolating extracellular vesicles,” form serum or plasma, lysing the cells, and measuring the amounts of biomarkers. All of these things are extra-solution activity, especially at the level of generality claimed. Further they are performed only to gather data to then perform the judicial exceptions. These things do not make the claims practically apply the judicial exceptions. See MPEP 2106.05 (g).
Claim 14, does not contain anything additional to the product of nature. Therefore- nothing is claimed to make it markedly different from what is found in nature.
Step 2B-Do the claims result in significantly more than the judicial exception?
There are no features instantly claimed which result in significantly more than the judicial exception.
Claims 1 & 8 both require treatment steps, however all that is claimed is a “therapeutic agent,” “directed against breast cancer cells.”
of all, the claim still reads as conditional in that a treatment is not always performed in the boundaries of the claim since the treatment is only performed, “upon confirmation”. Therefore- there is not always required.
Further—the claimed treatment of a “therapeutic agent,” “directed against breast cancer cells,” is akin to “administering a suitable antibiotic.” Though this is slightly more specific--- the MPEP points out that “administering a suitable medication.”
Therefore, at the level of generality claimed, this treatment is well understood, routine and conventional in the art (WURC). See MPEP 2106.05(d).
Claims 1 & 8 also require, “isolating extracellular vesicles,” form serum or plasma, lysing the cells, and measuring the amounts of biomarkers. All of these things are extra-solution activity, especially at the level of generality claimed. Further they are performed only to gather data to then perform the judicial exceptions. These things are also WURC.
Claim 14, does not contain anything additional to the product of nature. Therefore- nothing is claimed to make it markedly different from what is found in nature.
The other & dependent claims undergo a similar analysis
Claims 2-5, 8-11 do not change the matters above as they merely specify where the natural sample is taken from, what the biomarkers are, or the size of them. These things are all part of the natural compound itself and part of the natural correlation therefore it is still a natural sample and does not apply the judicial exception nor add significantly more.
Claims 6-7, & 12-13 specify how the detection is done is used to measure the biomarkers. These measurement methods and techniques however are routine and conventional and well understood method used to identify biomarkers in the art. Therefore- at the level of generality claimed- this does not provide practical application nor add significantly more to the judicial exception and does not change the matters above.
Claim 15 specifies the amount of antibodies or use of them. This does not add anything to make the natural compounds markedly different from what is found in nature so does not change matters.
Claim 16 specifies what the antibodies are. This does not add anything to make the natural compounds markedly different from what is found in nature so does not change matters.
Claims 17-18 specifies the amount of antibodies are attached to a solid support of detectable moiety. Especially at the level of generality claimed, this does not add anything to make the natural compounds markedly different from what is found in nature so does not change matters.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7, 14-15 & 17-18 are rejected under 35 U.S.C. 103 as being unpatentable by RAK in US 20130203081 in view of SCHETTINI in US 20150301058.
With respect to Claims 1, RAK teaches of a method for diagnosis of cancer and for monitoring the progression of cancer and/or the therapeutic efficacy of an anti-cancer treatment in a sample of a subject by detecting oncogenic and cancer related proteins in microvesicles, and to the use of an agent blocking exchange of microvesicles for treating cancer (abstract).
RAK further teaches of the cancer which is detected/diagnosed being breast cancer (paragraph 0043), of isolating extracellular vesicles from serum or plasmas to generate and isolate population of extracellular vesicles (Claim 8, paragraph 0013-0015), and lysing the sample to form a lysate (lysing the samples to generate a composition containing components of the extracellular vesicles (paragraph 0124, 0092).
RAK even further teaches of measuring the amount of cancer associate phosphoproteins like MEK1 in the composition/sample (Table 2-3).
RAK further teaches of comparison to a reference sample which can be from the same patient for that the level of biomarker is monitor for the progression, or treatment of the cancer (paragraph 0027, 0029). RAK further teaches of treating the patient for cancer with an anti-cancer treatment after the first measurement and that the treatment can be specific to breast cancer (paragraph 0028, 0104).
RAK teaches what is shown above for claim 1 and further teaches of measuring FAK in the composition as well (Tables 2-3). RAK does not teach of comparison to a “threshold”.
SCHETTINI is used to remedy this and further teaches of a method of assessing biomarkers for disease (abstract), wherein the disease can be breast cancer (paragraph 0044). SCHETTINI also teaches of detecting fibronectin and of comparing the biomarkers to a threshold level and also of the detection of MEK1 (Table 4, 5) to determine diagnosis (paragraph 0293).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect fibronectin and compare to a threshold as is done in SCHETTINI in the method of RAK due to the advantage this offers in aiding in a diagnosis (paragraph 0293).
With respect to Claim 2, RAK further teaches of what is shown above for claim 1 and further teaches of measuring FAK in the composition as well (Tables 2-3). RAK does not teach of measuring fibronectin.
SCHETTINI is used to remedy this and further teaches of a method of assessing biomarkers for disease (abstract), wherein the disease can be breast cancer (paragraph 0044). SCHETTINI also teaches of detecting fibronectin and of comparing the biomarkers to a threshold level and also of the detection of MEK1 (Table 4, 5) to determine diagnosis (paragraph 0293).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect fibronectin as is done in SCHETTINI in the method of RAK due to the advantage this offers in aiding in a diagnosis (paragraph 0293).
With respect to Claim 3, RAK teaches of detection in and isolation of extracellular vesicles from serum or plasmas to generate and isolate population of extracellular vesicles (Claim 8), but does not teach of the claim diameter for extracellular vesicles.
SCHETTINI is used to remedy this and teaches that the microvesicles can have a diameter of between 10 nm and 2000nm (paragraph 0040). This includes and therefore reads on the claimed range. SCHETTINI further teaches of the vesicles being exosomes (paragraph 0136).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use vesicles of the size of SCHETTINI in the method of RAK due to the advantage that using vesicles that have a “typical size,” in analysis gives for accuracy (SCHETTINI, paragraph 0138).
With respect to Claim 4, RAK teaches of the claims as shown above, but does not teach of serum albumin. SCHETTINI is used to remedy this and teaches of the plasma proteins coming from human serum albumin (paragraph 0159). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to purify from serum albumin as is done in SCHETTINI in the method of RAK due to the fact that depletion of background proteins in the human serum albumin/purification can facilitate more sensitive and accurate detection of the biomarkers (SCHETTINI, paragraph 0159).
With respect to Claim 5, RAK teaches that the extracellular vesicles include exosomes (paragraph 0087-0088).
With respect to Claim 6, RAK teaches of purification by filtration (paragraph 0033).
With respect to Claim 7, RAK teaches of the claims as shown above, but does not teach of serum albumin. SCHETTINI is used to remedy this and teaches of the plasma proteins coming from human serum albumin (paragraph 0159). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to purify from serum albumin as is done in SCHETTINI in the method of RAK due to the fact that depletion of background proteins in the human serum albumin/purification can facilitate more sensitive and accurate detection of the biomarkers (SCHETTINI, paragraph 0159).
With respect to Claims 14, RAK teaches of a method for diagnosis of cancer and for monitoring the progression of cancer and/or the therapeutic efficacy of an anti-cancer treatment in a sample of a subject by detecting oncogenic and cancer related proteins in microvesicles, and to the use of an agent blocking exchange of microvesicles for treating cancer (abstract).
RAK further teaches of the cancer which is detected/diagnosed being breast cancer (paragraph 0043), of isolating extracellular vesicles from serum or plasmas to generate and isolate population of extracellular vesicles (Claim 8, paragraph 0013-0015), and lysing the sample to form a lysate (lysing the samples to generate a composition containing components of the extracellular vesicles (paragraph 0124, 0092).
RAK even further teaches of measuring the amount of cancer associate phosphoproteins like MEK1 and FAK in the composition/sample (Table 2-3).
RAK further teaches of comparison to a reference sample which can be from the same patient for that the level of biomarker is monitor for the progression, or treatment of the cancer (paragraph 0027, 0029). RAK further teaches of treating the patient for cancer with an anti-cancer treatment after the first measurement and that the treatment can be specific to breast cancer (paragraph 0028, 0104).
RAK even further teaches of using a kit for detecting the cancer which comprises at least one antibody against an oncogenic proteins (paragraph 0023). Since RAK teaches of detection of both MEK1 And FEK (Table 1), this can read on antibodies that specifically bind to both MEK1 and FAK. Also- “at least one,” reads on “wherein the number of target proteins for the antibodies of the kit is no greater than 20.
With respect to Claim 15, RAK teaches of using a kit for detecting the cancer which comprises at least one antibody against an oncogenic proteins (paragraph 0023). Since RAK teaches of detection of both MEK1 And FEK (Table 1) , this can read on antibodies that specifically bind to both MEK1 and FAK. Also- “at least one,” reads on “wherein the number of target proteins for the antibodies of the kit is no greater than 10.
With respect to Claim 17, RAK teaches of the above, but does not teach of attaching a substrate to the antibody.
SCHETTINI is used to remedy this and teaches of using a binging agent to detect the biomarker/protein and that the binding agent is tethered to a substrate and further that the binding agent is labeled (paragraph 0039). SCHETTINI teaches that the binding agent can be an antibody (paragraph 0038).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use a substrate to bind the antibody and help with detection due to the advantage substrates offer for capturing and stable detection of molecules or biomarkers of interest (SCHETTINI, paragraph 0175).
With respect to Claim 18, RAK teaches of the above, but does not teach of attaching a detectable moiety to the antibody.
SCHETTINI is used to remedy this and teaches of using a binging agent to detect the biomarker/protein and that the binding agent is tethered to a substrate and further that the binding agent is labeled (paragraph 0039). SCHETTINI teaches that the binding agent can be an antibody (paragraph 0038).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use a substrate to bind the antibody and help with detection due to the advantage labels/detectable moieties offer for giving signals for detection of the molecules or biomarkers of interest (SCHETTINI, paragraph 0059).
Claims 8-13 & 16, are rejected under 35 U.S.C. 103 as being unpatentable by RAK in US 20130203081 in view of SCHETTINI in US 20150301058 and further in view of LIM in Ras-activated RSK1 phosphorylateds EBP50 to regulated its nuclear localization and promote cell proliferation.
With respect to Claims 8, RAK teaches of a method for diagnosis of cancer and for monitoring the progression of cancer and/or the therapeutic efficacy of an anti-cancer treatment in a sample of a subject by detecting oncogenic and cancer related proteins in microvesicles, and to the use of an agent blocking exchange of microvesicles for treating cancer (abstract).
RAK further teaches of the cancer which is detected/diagnosed being breast cancer (paragraph 0043), of isolating extracellular vesicles from serum or plasmas to generate and isolate population of extracellular vesicles (Claim 8, paragraph 0013-0015), and lysing the sample to form a lysate (lysing the samples to generate a composition containing components of the extracellular vesicles (paragraph 0124, 0092).
RAK even further teaches of measuring the amount of cancer associate phosphoproteins like MEK1 in the composition/sample (Table 2-3).
RAK further teaches of comparison to a reference sample which can be from the same patient for that the level of biomarker is monitor for the progression, or treatment of the cancer (paragraph 0027, 0029). RAK further teaches of treating the patient for cancer with an anti-cancer treatment after the first measurement and that the treatment can be specific to breast cancer (paragraph 0028, 0104).
RAK teaches what is shown above for claim 1 and further teaches of measuring FAK in the composition as well (Tables 2-3). RAK does not teach of comparison to a “threshold”.
SCHETTINI is used to remedy this and further teaches of a method of assessing biomarkers for disease (abstract), wherein the disease can be breast cancer (paragraph 0044). SCHETTINI also teaches of detecting fibronectin, actin beta (B-actin), c-raf and of comparing the biomarkers to a threshold level and also of the detection of MEK1 (Table 4, 5, paragraph 0726) to determine diagnosis (paragraph 0293). SCHETTINI further teaches of detection of CDH2( which is N-Cadherin)(paragraph 0025).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect fibronectin and compare to a threshold as is done in SCHETTINI in the method of RAK due to the advantage this offers in aiding in a diagnosis (paragraph 0293).
RAK and SCHETTINI do not teach of the detection of P90RSK_pT573 (Phospho-RSK1 (Thr573)).
LIM is used to remedy this and teaches that the differential subcellular localization of EBP50 leads to it’s controversial role as tumor suppersor OR facilitator. RSK1 binds to EBP50 and phosphorylates it (abstract).
LIM further teaches that the p90 ribosomal S6 kinase (RSK) is a family of AGC kinases consists of four isoforms (RSK1-4), which have two kinase domains, an extracellular signal-regulated kinase (ERK) docking motif (D domain), and a C-terminal PDZ binding motif [20, 21]. The C-terminal kinase domain (CTKD) of RSK is responsible for its activation through autophosphorylation, whereas the N-terminal kinase domain (NTKD) is essential for the phosphorylation of its substrates [20].
Upon stimulation of cells with growth factors, ERK is phosphorylated downstream of the Ras cascade. Then, activated ERK initiates activation of RSK, via docking at the D domain and phosphorylating RSK at threonine 573 [22, 23] (Page 10284, column 1, paragraph 2) (all this reads on (Phospho-RSK1 (Thr573)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect (Phospho-RSK1 (Thr573)) as is described in LIM in the methods of RAK and SCHETTINI since the RSK1 phosphoylation mechanisms is important to facilitate cellular proliferation in things such as cancers and expecially breast cancers (Page 10283, right column -Page 10284, column 1, paragraph 3).
With respect to Claim 9, RAK teaches of detection in and isolation of extracellular vesicles from serum or plasmas to generate and isolate population of extracellular vesicles (Claim 8), but does not teach of the claim diameter for extracellular vesicles.
SCHETTINI is used to remedy this and teaches that the microvesicles can have a diameter of between 10 nm and 2000nm (paragraph 0040). This includes and therefore reads on the claimed range. SCHETTINI further teaches of the vesicles being exosomes (paragraph 0136).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use vesicles of the size of SCHETTINI in the method of RAK due to the advantage that using vesicles that have a “typical size,” in analysis gives for accuracy (SCHETTINI, paragraph 0138).
With respect to Claim 10, RAK teaches of the claims as shown above, but does not teach of serum albumin. SCHETTINI is used to remedy this and teaches of the plasma proteins coming from human serum albumin (paragraph 0159). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to purify from serum albumin as is done in SCHETTINI in the method of RAK due to the fact that depletion of background proteins in the human serum albumin/purification can facilitate more sensitive and accurate detection of the biomarkers (SCHETTINI, paragraph 0159).
With respect to Claim 11, RAK teaches that the extracellular vesicles include exosomes (paragraph 0087-0088).
With respect to Claim 12, RAK teaches of purification by filtration (paragraph 0033).
With respect to Claim 13, RAK teaches of the claims as shown above, but does not teach of serum albumin. SCHETTINI is used to remedy this and teaches of the plasma proteins coming from human serum albumin (paragraph 0159). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to purify from serum albumin as is done in SCHETTINI in the method of RAK due to the fact that depletion of background proteins in the human serum albumin/purification can facilitate more sensitive and accurate detection of the biomarkers (SCHETTINI, paragraph 0159).
With respect to Claim 16, RAK teaches of the invention as shown above. RAK teaches of using a kit for detecting the cancer which comprises at least one antibody against an oncogenic proteins (paragraph 0023). Since RAK teaches of detection of both MEK1 And FEK (Table 1), this can read on antibodies that specifically bind to both MEK1 and FAK. Also- “at least one,” reads on “wherein the number of target proteins for the antibodies of the kit is no greater than 10. See claim 8 rejection above for detection with antibodies of fibronectin, B-Actin, C-Raf, N-Cadherin.
RAK and SCHETTINI do not teach of the detection of P90RSK_pT573 (Phospho-RSK1 (Thr573)).
LIM is used to remedy this and teaches that the differential subcellular localization of EBP50 leads to it’s controversial role as tumor suppersor OR facilitator. RSK1 binds to EBP50 and phosphorylates it (abstract).
LIM further teaches that the p90 ribosomal S6 kinase (RSK) is a family of AGC kinases consists of four isoforms (RSK1-4), which have two kinase domains, an extracellular signal-regulated kinase (ERK) docking motif (D domain), and a C-terminal PDZ binding motif [20, 21]. The C-terminal kinase domain (CTKD) of RSK is responsible for its activation through autophosphorylation, whereas the N-terminal kinase domain (NTKD) is essential for the phosphorylation of its substrates [20].
Upon stimulation of cells with growth factors, ERK is phosphorylated downstream of the Ras cascade. Then, activated ERK initiates activation of RSK, via docking at the D domain and phosphorylating RSK at threonine 573 [22, 23] (Page 10284, column 1, paragraph 2) (all this reads on (Phospho-RSK1 (Thr573)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention in the to detect and use antibody for as is done in SCHETTINI (Phospho-RSK1 (Thr573)) as is described in LIM in the methods of RAK and SCHETTINI since the RSK1 phosphoylation mechanisms is important to facilitate cellular proliferation in things such as cancers and expecially breast cancers (Page 10283, right column -Page 10284, column 1, paragraph 3).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758