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 17/912902 filed 09/20/2022.
Claims 1-14 are pending and have been fully considered.
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 1-14 are directed to non-statutory subject matter.
The invention of instant claims for independent claim 1 is drawn towards a method for diagnosing immediate hypersensitivity reaction. For independent Claim 12, it is drawn towards a method of determining the, “risk,” of a small compound or drug to elicit immediate hypersensitivity reaction (IHR).
However, as instantly considered as a whole both independent claims are drawn towards the judicial exceptions which are a combination of a natural correlation and abstract ideas.
Through 101, inquiry:
Inquiry: Are the claims directed to a statutory category of invention?
Yes, independent Claims 1 & 12 are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Yes, independent Claims 1 & 12 involve judicial exceptions.
Independent Claim 1 requires, “diagnosing,” immediate hypersensitivity reaction (IHR) in the preamble and step (d), based on detection of mast cell activation or degranulation. This diagnosis is both a natural correlation (mass cell activation= IHR or not), and also an abstract idea/ math of the correlation. Further, the “attributing,” in step (d), is a mental process which is also an abstract idea.
Independent Claim 12 requires, “determining risk” of eliciting IHR/ immediate hypersensitivity reaction (IHR) in the preamble and in step (d), being, “indicative,” of risk, based on detection of mast cell activation or degranulation. Both determining risk and indication are mental processes which are abstract ideas. Since this is based on mas cell detection, though not explicitly claimed, a natural correlation (mast cell presence or amount= diagnosis of IHR or not) is also implicitly in the claims even though a positive method step of performing the diagnosis is not included. This also includes an abstract idea/ math of the correlation.
Step 2A, Prong 2: Has the natural correlation or abstract idea been integrated into a particular practical application?
In Claims 1 & 12, there is no integration of the claimed judicial exceptions into a practical application.
In addition to the judicial exception parts of the claim, Claim 1 contains the additional steps of:
Contacting mast cells with serum
Contacting mast cells with a small compound or a drug
Detecting mast cell activation or degranulation.
For (a), (b), and (c), these steps are all considered extra-solution activity performed to gather data to accomplish the judicial exception and therefore do not practically apply the judicial exceptions. See MPEP 2106.05(g). Further- nothing is done to practically apply the judicial exceptions after the data is gathered, therefore there is no practical application.
In addition to the judicial exception parts of the claim, Claim 12 contains the additional steps of:
Contacting mast cells with serum (wherein the serum is from a subject diagnosed with IHR to a first compound)
Contacting mast cells with a second small compound or a drug
Detecting mast cell activation or degranulation.
As in Claim 1, for Claim 12, (a), (b), and (c), these steps are all considered extra-solution activity performed to gather data to accomplish the judicial exception and therefore do not practically apply the judicial exceptions. See MPEP 2106.05(g). This remains the case, even though applicant is screening a second compound. Further- nothing is done to practically apply the judicial exceptions after the data is gathered, therefore there is no practical application.
Further for both Claims 1 & 12, no particular treatment is claimed. See MPEP 2106.04 (d)(2) & Vanda memorandum with respect to particular treatment.
Step 2B: Do the claims recite any elements which are significantly more than the natural correlation or abstract idea?
For Claims 1 & 12, the additional steps (a), (b), and (c), outlined above are not considered to be significantly more than the claimed judicial exceptions.
For (a), contacting mast cells with serum and small compounds or drugs is well understood, routine and conventional (WURC) in the art. The same thing applies to detecting of mast cell activation or degranulation. This is the case especially at the level of generality claimed.
Therefore, as claimed all these steps are WURC and standard laboratory technique and are not sufficient to show an improvement in technology or add significantly more. See MPEP 2106.05 (d) & (a).
The dependent claims are reviewed for additional limitations dependent on the independent claim above.
Claims 2 & 3 just narrows down to one of two options presented in Claim 1, therefore does not change the analysis with respect to 101 from Claim 1.
Claim 4 specifies the molecular weight of the small compound. This is a material property. Therefore, this does not change the analysis with respect to 101 as it does not practically apply at step 2 A/s nor add significantly more at step 2b.
Claim 5 specifies that the small compound is diagnostic or therapeutic. This really gives no additional information, except for potentially the use of the compound, but is not claimed as used. Therefore, this does not change the analysis with respect to 101 as it does not practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 6 specifies that the small molecule is used in a “non-toxic,” concentration,” however doesn’t specify what the small molecule is. Therefore, this does not change the analysis with respect to 101 as it does not practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 7-8 specifies that the mast cells used are cultured donor cells (obtained through isolating peripheral blood, and progenitor cells, and culturing the cells). With respect to this, they are still mast cells and natural compounds. Further the claimed, isolating and culturing is extra-pre-solution activity and also is WURC. Therefore, this does not change the matters above as it does nothing to practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 9 specifies that the activation or degranulation is detected by detecting unspecified biomarkers. This does not change the matters above as it does nothing to practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 10 specifies that degranulation is detected by determining overexpression of CD63 antigen on cell surface. As claimed, this is a biomarker, which is part of the natural correlation highlighted in Claim 1. Therefore, this does not change the matters above as it does nothing to practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 11 specifies that the mast cells are pre-incubated with one or more of the claimed priming cytokines. As claimed, however this pre-incubation is still extra pre-solution activity and is also WURC at the level of generality claimed. Therefore, this does not change the matters above as it does nothing to practically apply at step 2 A/s nor add significantly more at step 2B.
Claim 13, specifies that the serum is from the patient/subject who IHR is supposed to be predicted in. That the samples are from a person and a natural samples is part of the judicial exception of a natural correlation itself. Therefore, this does not change the analysis given for Claim 12 above.
Claim 14 adds a second small compound, but doesn’t claim what it is. Therefore, this does not change the matters above as it does nothing to practically apply at step 2 A/s nor add significantly more at step 2B.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to Claim 1, “immediate,” is a relative term and not defined by the claim and therefore is unclear. Further, “particular,” is also a relative term and not defined by the claim as is also unclear. What one person would consider to be particular or immediate would be different from what others might think is so.
With respect to Claim 4, it is unclear by using the term “preferably,” if applicant is intending to further limit the claim.
All other claims dependent on Claims 1 & 4 are rejected by virtue of being dependent on unclear claims.
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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable by LUDWIG in Measurement of mas cell and basophil activation in vitro as means for investigation of drug hypersensitivity in view of BAHRI in Mast cell activation test in the diagnosis of allergic disease and anaphlaxis (both references cited on IDS dated 09/20/2022).
With respect to Claims 1 & 12, LUDWIG teaches of a test for investigating/diagnosing drug hypersensitivity (diagnosing risk of drug hypersensitivity), particularly immediate hypersensitivity IgE mediated responses (page 17, paragraphs 2-3) by the measurement of beta-hexosaminidase release from passively sensitized cells.
The process includes incubating mast cells of the cell line LAD2 and basophil cell lines were with patient serum. Then, a drug or another stimulus was added and the supernatant collected after 45 min. Then, beta-hexosaminidase was measured. The same was performed without patient serum. A positive control with a calcium ionophore was also performed (page 53, Figure 2.1, page 50, 2.3).
Though LUDWIG teaches that the methods are used for investigating immediate hypersensitivity, in case it’s not clear that the mast cell activation is attributed to the diagnosis, BAHRI is used to remedy this.
BAHRI teaches of a comparison of a mast cell activation test (MAT) in the diagnosis of allergic disease and anaphylaxis with other existing tools. Human blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose- dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D 2 and B-hexosaminidase release) (fig 1). It would have been obvious to one of ordinary skill to correlate mast cell activation with disease as is done in BAHRI in the method of LUDWIG due to the advantage MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests (BAHRI, abstract; figure 1; page 490, column 1, last lines to page 491, column1, first paragraph).
For Claim 12, LUDWIG and BAHRI do not specifically call out that the serum sample is obtained from subjects already diagnoses with IHR for a first compound for determination of a risk from a second compound.
However, as LUDWIG teaches of monitoring response of multiple drugs/compounds (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72), and of using samples from multiple patients and of repeating the experiment (Page 88, last paragraph, Figure 4.8). Therefore, LUDWIG teaches of monitoring a first and second compound or drug as claimed and of performing the analysis multiple times and repeating on the same patients. Therefore, repeating with a second compound/drug on a patient who is found to be sensitive to a first compound/drug is made obvious to one of ordinary skill in the art from these teachings.
With respect to Claims 2-3, LUDWIG teaches of adding a drug or other stimuli such as isopropyl alcohol which can be considered a “small molecule,” through broadest reasonable interpretation and of contacting of the mast cells and the drug or small molecule (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72).
With respect to Claim 4, LUDWIG teaches of adding a drug or other stimuli such as isopropyl alcohol which can be considered a “small molecule,” through broadest reasonable interpretation and of contacting of the mast cells and the drug or small molecule (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72). Isopropyl alcohol has a molecular weight of 60.1 Daltons, so this reads on being in the claimed range of “at most 9000 Da.”
With respect to Claim 5, LUDWIG teaches of adding a drug (which can be considered a therapeutic compound) and a small molecule through broadest reasonable interpretation, or other stimuli and of contacting of the mast cells and the drug or small molecule (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72).
With respect to Claim 6, LUDWIG teaches of adding a drug or other stimuli and of contacting of the mast cells and the drug or small molecule. LUDWIG does not teach of the concentration used being toxic so it is a non-toxic concentration through broadest reasonable interpretation (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72).
With respect to Claim 7, LUDWIG teaches of the mast cells being cultured donor mast cells- so the cells are from donors (since cells are a “gift,” they are donor cells and they are also cultured) (Page 49, last paragraph, Page 29-30, the paragraph bridging the pages).
With respect to Claim 8, LUDWIG teaches of the above, but does not teach of the claimed sample processing.
BAHRI is used to remedy this. BAHRI teaches of isolating peripheral mononuclear cells from healthy donors (graphical abstract, Page 487, column 1, paragraph 2). BAHRI teaches of purifying the CD34+ cells from mononuclear cells (page 487, column 1, paragraph 3). BAHRI even further teaches of culturing CD34+ cells (Page 487, column 1, paragraph 3).
It would have been obvious to one of ordinary skill to process the cells as is done in BAHRI in the method of LUDWIG due to the advantage this offers in using the diagnostic tool (Page 487, column 1, paragraph 2).
With respect to Claim 9, LUDWIG teaches of detection activation of degranulation by detecting biomarkers secreted such as chymase and heparin (Page 35 & 36, whole page).
With respect to Claim 10, LUDWIG teaches of detection activation of degranulation by detecting biomarkers and of detecting upregulation of CD63 on basophil cells (Page 94, whole page).
LUDWIG does not teach of detection of it on mast cells.
BAHRI is used to remedy this. BAHRI further teaches of measuring degranulation of hMCs (mast cells) by detecting CD63+ (Figure 2 and associated description). It would have been obvious to one of ordinary skill in the art to detect degranulation of CD63+ as is done in BAHRI in the method of LUDWIG due to the advantage detecting mast cells has since they are known to tbe the main effector cells in patients with allergic reactions (Page 486, column 2, paragraph 4).
With respect to Claims 11, LUDWIG teaches of incubating the mast cells with IL-4 (Page 24, last paragraph).
With respect to Claims 13-14, LUDWIG teaches of a test for investigating/diagnosing drug hypersensitivity, particularly immediate hypersensitivity IgE mediated responses (page 17, paragraphs 2-3) by the measurement of beta-hexosaminidase release from passively sensitized cells.
The process includes incubating mast cells of the cell line LAD2 and basophil cell lines were with patient serum. Then, a drug or another stimulus was added and the supernatant collected after 45 min (in vitro analysis). Then, beta-hexosaminidase was measured. The same was performed without patient serum. A positive control with a calcium ionophore was also performed (page 53, Figure 2.1, page 50, 2.3).
LUDWIG teaches of adding a drug (multiple drugs are shown so can be first and second drug or compound) (which can be considered a therapeutic compound) and a small molecule through broadest reasonable interpretation, or other stimuli and of contacting of the mast cells and the drug or small molecule (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72
Though LUDWIG teaches that the methods are used for investigating immediate hypersensitivity, in case it’s not clear that the mast cell activation is attributed to the diagnosis, BAHRI is used to remedy this.
BAHRI teaches of a comparison of a mast cell activation test (MAT) in the diagnosis of allergic disease and anaphylaxis with other existing tools. Human blood-derived MCs sensitized with sera from patients with peanut, grass pollen, and Hymenoptera (wasp venom) allergy demonstrated allergen-specific and dose- dependent degranulation, as determined based on both expression of surface activation markers (CD63 and CD107a) and functional assays (prostaglandin D 2 and B-hexosaminidase release) (fig 1). It would have been obvious to one of ordinary skill to correlate mast cell activation with disease as is done in BAHRI in the method of LUDWIG due to the advantage MAT was found to have superior discrimination performance compared with other testing modalities, including component-resolved diagnostics and basophil activation tests (BAHRI, abstract; figure 1; page 490, column 1, last lines to page 491, column1, first paragraph).
For Claim 12, LUDWIG and BAHRI do not specifically call out that the serum sample is obtained from subjects already diagnoses with IHR for a first compound for determination of a risk from a second compound.
However, as LUDWIG teaches of monitoring response of multiple drugs/compounds (Page 53, Figure 2.1, Page 67, paragraphs 2-3, 4.3.1 starting on Page 72), and of using samples from multiple patients and of repeating the experiment (Page 88, last paragraph, Figure 4.8). Therefore, LUDWIG teaches of monitoring a first and second compound or drug as claimed and of performing the analysis multiple times and repeating on the same patients. Therefore, repeating with a second compound/drug on a patient who is found to be sensitive to a first compound/drug is made obvious to one of ordinary skill in the art from these teachings.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758