DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent
provisions.
Claims 1-60 have been canceled. Claim 61 has been amended. Claims 62-79 have been added. Claims 61-79 are pending and examined on the merits.
Claim Objections
Claim 63 is objected to because of the following informalities: “precipitin reactions” is listed twice. Appropriate correction is required.
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 of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 61-79 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) determining whether administering the therapy resulted in a decrease in the amount of cancer stem cells to indicate that the therapy has anti-cancer stem cell activity which is the third category of the abstract idea grouping of Section I of the eligibility guidance of 2019 described as 3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) . This judicial exception is not integrated into a practical application because the conclusion that the therapy has anti-cancer stem cell activity is also a mental activity . The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because dependent claims 62-74 requiring various assays to determine the amount of cancer stem cells are well-understood, routine, and conventional methods, which contribute to the step of data gathering allowing for the step of abstract reasoning. Dependent claim 75 which requires a pretreatment step is recited at a high level of generality and also contributes to the data gathering. Dependent claims 76 and 77 recite the source for samples obtained from a human which are well-understood, routine, and conventional sources recognized in the art as a source for cellular material. Claim 78 recite various solid tumors by the organ in which they occur in combination with leukemias by histological type and claim 79 recites well know generic therapies. These directives provide only for the data gather step and do not add significantly more to the judicial exception because they provide no practical application based on the conclusion of the mental processes.
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 61-79 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.
(A)Claim 61 is vague and indefinite in the recitation in part (ii) of monitoring cancer stem cells in or from the human patient “prior to, during, and/or following therapy”. Given the plain language of the claim, the “and/or” allows for “prior to”, “during” and “following” as separate embodiments. It is unclear how monitoring cancer stem cells only “prior to” the therapy can provide a conclusion that the administered therapy resulted in a decrease in the amount of the cancer stem cells, because it would be necessary to monitor the cancer stem cells “during” or “following” the therapy to make the determination that the therapy resulted in a decrease in the amount of cancer stem cells. Further, the monitoring of cancer stem cells “during” or following” therapy cannot provide a conclusion that the administered therapy resulted in a decrease in the amount of cancer stem cells without knowledge of the amount of cancer stem cells prior to the administered therapy.
(B)Claim 61 is vague and indefinite in the recitation of “ii)monitoring cancer stem cells” followed by (iii) determining if the therapy resulted in a decrease in the amount of cancer stem cells. It is unclear what is being “monitored” in the cancer stem cells in part iii beyond that of measuring a quantitative amount of the cancer stem cells required to determine if the therapy resulted in a decrease in the amount of cancer stem cells in step iii).
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 72 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the determination of the amount of cancer stem cells in vivo by carrying out imaging using an imaging agent, does not reasonably provide enablement for the determination of the amount of cancer stem cells in vivo by carrying out imaging without an imaging agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
When given the broadest reasonable interpretation, claim 72 encompasses in vivo imaging without the use of an imaging agent, because dependent claim 73 specifies that an imaging agent is used. Therefore, because the dependent claim 73 must further limit claim 72, it is reasonable to conclude that claim 72 encompasses in vivo imaging without the use of an imaging agent.
Clarke et al (U.S. 2002/0119565, reference of the IDS filed 11/11/2022) teach that cancer stem cells are identified by cell surface markers and that these cell surface markers can be recognized by reagents that specifically bind to the cell surface markers (paragraph [0053]). The instant specification provides no teachings or guidance for carrying out in vivo imaging without the use of a detectable agent bound to cancer stem cells either directly or indirectly. One of skill in the art would be subject to undue experimentation without reasonable expectation of success in order to carry out the broadly claimed method.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 61-67, 70, 71, 75, 76, 78 and 79 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al (U.S. 2002/0119565, reference of the IDS filed 11/11/2022).
Claim 1 is drawn in part to a method of assaying or screening a therapy for anti-cancer stem cell activity comprising (i) administering the therapy to a human with cancer; (ii) monitoring cancer stem cells in said human, or from said human prior to and following therapy
Claim 62 requires that the amount of cancer stem cells be determined by an immunoassay. Claim 63 specifies, in part, that the immunoassay of claim 62 includes an ELISA, “fluorescent immunoassays, flow cytometry and FACS. Claim 64 specifies that the amount of cancer stem cells in claim 61 is determined using a flow cytometer. Claim 65 requires that in the method of claim 64, the amount of cancer stem cells is determined with one or more antibodies that bind cell surface markers. Claim 66 requires that the cancer stem cells are contacted with one or more dyes prior to detection in the flow cytometer. Claim 67 specifies that the amount of cancer stem cells is determined by immunohistochemistry
Claim 70 requires that the amount of cancer stem cells is determined by culturing a sample obtained from the human and quantitating the cancer stem cells in an in vitro assay. Claim 71 specifies that an immunocompromised mouse engraftment model is used to determine the amount of cancer stem cells in claim 70.
Claim 75 requires that a sample is obtained from the human in the method of claim 61, and said sample is subjected to one or more pretreatment steps prior of determining the amount of cancer stem cells in the sample.
Claim 78 requires that the cancer is selected from AML, breast cancer, brain cancer, ALL, ovarian cancer, multiple myeloma, CML, CLL, lymphoma, melanoma, ependymoma, prostate cancer, lung cancer, thyroid cancer, colorectal cancer, pancreatic cancer, bladder cancer, MDS, hairy cell leukemia, and stomach cancer.
Claim 79 specifies that the therapy of claim 61 is, in part, chemotherapy, hormonal therapy, and/or radiation therapy.
Clarke et al teach that the invention allows for the use of FACS to identify, isolate and characterize a cell population within the tumor mass having stem cell properties of extensive proliferation and the ability to give rise to the other tumor cell types (paragraph [0008]). Clarke et al teach that solid tumor stem cells are the truly tumorigenic cells that are capable of re-establishing a tumor following treatment. (paragraph [0008]). Clarke et al teach that the invention provides for the testing of patients‘ tumor sensitivity to known therapies as well as for the identification if new anti-cancer therapeutic agents (paragraph [0011]). Clarke et al teach that in order to effectively treat cancer and achieve higher cure rates, anti-cancer therapies must be directed against solid tumor stem cells and that current therapies directed against the bulk tumor population may be ineffective for eradicating solid tumor stem cells (paragraph [0074]). Clarke et al teach that radiation therapy, chemotherapy, and hormonal therapy are “traditional” modes of therapy(paragraph [0005]) and which one of skill in the art would recognize as “known therapies” for the testing of patients‘ tumor sensitivity thereto, and meets the limitations of chemotherapy, hormonal therapy and radiation therapy in claim 79
Clarke et al teach that FACS methods using CD44 alone can enrich solid tumor stem cells at least 2-fold (see, EXAMPLE 1 and 3); FACS methods using B38.1 and CD24 can enrich for solid tumor stem cells 5-6 fold (see, EXAMPLE 3) and that enrichment using additional markers can enrich 10-fold or more (paragraph [0079]) which meet the limitations of claims 62-64.
Clarke et al teach an antibody cocktail that leads to the greatest purification of the putative tumorigenic cell by FACS is anti-38.1-APC, anti-CD44-FITC, and anti-CD24-PE, anti-CD3-cytochrome, anti-CD2-cytochrome, anti-CD10-cytochrome,, anti-CD14-cytochrome, anti-CD16-cytochrome, anti-CD31 -cytochrome, CD45-cytochrome, CD140b-cytochrome, anti-CD64-cytochrome, anti-ESA-Phar-red and the stain 7AAD (paragraph [0255]) which meets the limitations of claim 65 for antibodies which bind cell surface markers and claim 66 for contact of the stem cells with one or more dyes prior to detection in the flow cytometer because 7AAD is a dye..
Clarke et al teach a method for detecting the presence of solid tumor stem cells, comprising the steps of: (a) contacting the cells from a solid tumor with a reagent that binds to a positive marker for solid tumor stem cells; and (b) detecting the contact between the reagent and the cells from the solid tumor, wherein an increased detection of the number of contacted cells as compared with the number of contacted cells in a benign tumor identifies the tumor as containing solid tumor stem cells, wherein the detection is by flow-cytometry or immunohistochemistry (claim 123 of ‘565) which meets the limitation of claim 67.
Clarke et al teach that in vivo proliferation of solid tumor stem cells can be accomplished by injection of solid tumor stem cells into immunocompromised mice, such as SCID mice, Beige/SCID mice or NOD/SCID mice (see, EXAMPLES) and that NOD/SCID mice are injected with the varying number of cells and observed for tumor formation (paragraph [0083]). Clarke et al teach that samples of human breast tumors were received within an hour after the surgeries; the tumors were cut up with scissors into small pieces, and the pieces were then minced and the minced pieces are implanted into the mice (paragraph [0085]) which meets the limitations of claims 71-72, which meets the limitation of a sample which is a tumor biopsy in claim 76..
Clarke et al teach that cells can be obtained from solid tumor tissue by dissociation of individual cells and that the dissociated cells dissociated tumor cells can be placed into any known culture medium capable of supporting cell growth (paragraphs [0093]-[0094]). Clarke et al teach that a particular patient's solid tumor stem cells, once they have been proliferated in vitro, can be analyzed and screened (paragraph [0098]) which meets the limitations of claim 70.
Clarke et al teach solid tumors from which solid tumor stem cells can be isolated or enriched for according to the invention include, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, lung carcinoma, bladder carcinoma, and melanoma, (paragraph [0040]) which meets the limitations of claim 78. Clarke et al also teach the solid tumor may be located in or on the lining of the central nervous system, such as, for example, the spinal cord, spinal roots or brain (paragraph [0120]).
Clarke et al teach the limitations of the instant claims with respect to testing of patients‘ tumor sensitivity to known therapies as well as the identification if new anti-cancer therapeutic agents with the exception that Clarke et al do not specifically teach determining the amount of cancer stem cells in a sample from the patient before the administration of the chemotherapeutic, hormonal or radiation therapy, and determining the amount of cancer stem cells in a sample from the patient before and after or during the chemotherapeutic, hormonal or radiation therapy, wherein the cells are cultured in vitro or in vivo in the immunocompromised mice. However, it would have been prima facie obvious at the time that the invention was made to do so in order to determine to test patient’s tumor to sensitivity to known therapeutic or new therapeutic compounds by quantitating the amount of cancer stem cells before and after treatment. One of skill in the art would understand that quantitation would be necessary in cases where the therapy did not result in total elimination of the cancer stem cells, but rather reduced the cancer stem cells to a level which was lower than prior to the therapy Oner of skill in the art would be interesting in knowing the degree to which the reduction occurred so as to further determine the next step in the patients treatment.
Claims 61-67, 70, 71-76, 78 and 79 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al (U.S. 2002/0119565, reference of the IDS filed 11/11/2022) in view of Bergstein (U.S. 6,004,528, reference of the IDS filed 11/11/2022) and Nicolotti et al (U.S.4,659,839, reference of the IDS filed 11/11/2022).
Claim 72 embodies the method of claim 61, wherein the amount of tumor stem cells are determined by in vivo imaging. Claim 73 requires that the in vivo imaging uses an imaging agent. Claim 74 requires, in part, that the imaging agent is an antibody or antibody fragment that binds to a cancer stem cell, wherein the antibody or fragment thereof is attached to a detectable agent including a radionuclide.
The teachings of Clarke et al render obvious the limitations of claims 61-67, 70, 71, 75, 76, 78 and 79, for the reasons set forth above. Clarke et al does not specifically teach that in the method of claim 61, the cancer stem cells are imaged in vivo to determine whether administration of the therapy resulted in a decrease in the amount of cancer stem cells to indicate that the therapy has anti-cancer stem cell activity.
Bergstein teaches a method of aiding the diagnosis of cancer comprising detecting the presence or absence of a cancer stem line in an individual comprising quantifying in vivo or in vitro the number of stem cells in an individual or in a tissue sample obtained from an individual and comparing the number of stem cells to that of a normal individual (claim 1), thus fulfilling the limitation of instant claims 1, 2 and 6. Bergstein teaches quantification in vivo (claim 1), thus fulfilling the specific limitation of "in vivo" imaging of instant claim 17. Bergstein teaches detection by flow cytometry of immunohistochemistry (claim 8) thus fulfilling the limitations of instant claim 9 and 12.
Bergstein teaches the detection of the cancer stem cell by radionuclide imaging (claim 7), but does not specifically state if the radionuclide imaging is in vivo or in vitro, nor does Bergstein teach the imaging agent is an antibody fragment that binds to a cancer stem cell wherein the antibody fragment is attached to a radionuclide.
Nicolotti et al teach that the use of radionuclide metal ions in in vivo diagnostic applications is well known in the art (column 1, lines 24-28). Nicolotti et al teach that radiolabeled antibody fragments rather than radiolabeled whole antibodies are more useful for in vivo diagnostic applications because the antibody fragments are better able to penetrate to the desired target site and use of the antibody fragments may minimize problems associated with immunogenicity in vivo (column1, lines 59-65). Nicolotti et al teach that an antibody complexed with a radionuclide through a chelating group to from an antibody-radionuclide conjugate can be used in vivo as a diagnostic imaging agent (column 3, lines 17-22).
It would have been prima facie obvious at the time that the clamed invention was made to detect the cancer stem cells of Clarke et al in vivo according to the method of Bergstein, wherein the cancer stem cells is detected using an antibody fragment that specifically binds to a marker expressed on the cancer stem line, wherein the antibody fragment is chelated with a radionuclide. One of skill in the art would have been motivated to do so by the teachings of Bergstein requiring in part, the quantification in vivo of the number of stem cells (claim 1(i) of ‘528) and the use of radionuclide imaging (claim 7 of ‘528) in light of the teachings of Nicolotti et al regarding the use of antibody fragments chelated to radionuclides for in vivo diagnostic applications. It is noted that Bergstein narrowly defines a cancer stem line as having symmetrically dividing stem cells (claim 1 of ‘528) as opposed to asymmetrically diving normal stem cells. Clarke et al teach that solid tumor stem cells likely divide both symmetrically and asymmetrically, such that symmetric cell division is not an obligate property (paragraph [0052]). However, the teachings of Bergstein is obviously analogous art and one of skill in the art would be motivated to use the techniques taught by Bergstein for the detection of the more broadly defined cancer stem cells taught by Clarke et al. One of skill in the art would have been motivated to detect the cancer stem cells in vivo using a chelated radionuclide in order to potentially image metastatic lesions comprising the cancer stem cells.
Claims 61-68, 70, 71, 75, 76, 78 and 79are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al (U.S. 2002/0119565) in view of Yuan et al (Oncogene, 2004, Vol. 23, pp. 9392-9400).
The teachings of Clarke et al render obvious the limitations of claims 61-67, 70, 71, 75, 76, 78 and 79, for the reasons set forth above. Clarke et al does not specifically teach that in the method of claim 61, the amount of cancer stem cells is determined using a sphere forming assay. Clarke et al teach that the tumors treated by the inventive methods include brain cancer (paragraph [0120]).
Yuan et al teach that brain tumor stem cells from glioblastoma multiforme for neurospheres (abstract). Yuan et al teach that these tumor stem cells can reform spheres even after the induction of differentiation and that these cells of the GBM derived spheres were able to form tumors and generate both neurons and glial cells after in vivo implantation and are thus tumor stem cells (abstract). Yuan et al teach that primary cultures grown as monolayers produce spheres when cultured under conditions known to be permissive for stem cell proliferation (page 9393, first column, lines 6-12).
It would have been prima facie obvious at the time the claimed invention was made to assay for brain tumor stem cells by forming neurospheres from brain tumor tissue and quantitating the amount oof tumor stem cells based on the size and number of spheres both before and after therapy. One of skill in the art would have been motivated to do so because the spheres form spontaneously when cultured under conditions known to be permissive for stem cell proliferation and thus do not involve an isolation step based on an antibody cocktail.
Claims 61-67, 69-71 and 75-79 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Clarke et al (U.S. 2002/0119565) in view of Bergstein (U.S. 6,004,528) and Terpstra et al (Blood, 1996, Vol. 87, pp. 2187-2194, reference of the IDs filed 11/11/2022).
Claim 69 requires that the amount of cancer stem cells is determined in the method of claim 61 using a cobblestone assay.
Clarke et al teach the limitations of claims 61-67, 70, 71, 75, 76, 78 and 79, for the reasons set forth above. Clark et al do not teach that the inventive stem cells can be hematopoietic stem cells.
Bergstein teaches that suitable cancer stemline antigens to be targeted by monoclonal antibodies may be identified by, e.g. cloning adult stem cells of various tissue types in order to determine their expression profiles and complement of cell surface antigens for a particular tissue and assuming that a proportion of these cell products will also be present in a cancer stemline derived from these stem cells and that the cloning of adult stem cells of hematopoietic origin is a technique previously described and now done routinely by those skilled in the art (column 32, lines 7-16). Thus, one of skill in the art would reasoanbley conclude that hematopoietic cancers comprise hematopoietic cancer stem cells analogous to the solid tumor stem cells of Clarke et al.
It would have been prima facie obvious at the time the invention was made would have been prima facie obvious at the time that the invention was made to do so in order to determine to test patient’s tumor to sensitivity to known therapeutic or new therapeutic compounds by quantitating the amount of cancer stem cells before and after treatment. One of skill in the art would understand that quantitation would be necessary in cases where the therapy did not result in total elimination of the cancer stem cells, but rather reduced the cancer stem cells to a level which was lower than prior to the therapy Oner of skill in the art would be interesting in knowing the degree to which the reduction occurred so as to further determine the next step in the patients treatment.
Regarding claim 69 specifying a cobblestone assay, and claims 76 and 77 requiring that the sample obtained from the human was a biological fluid and blood, respectively, Terpstra et al teach a method wherein cobblestone areas were quantified after plating unseparated AML cells, the CD34- fraction or the CD34+ fraction (page 2191, under the heading “CAFC assay”, and Figure 5), wherein the sample of AML cells was obtained from the peripheral blood (page 2187, lines 1-4 under the heading “Materials and Methods”). The separation of the AML cells into the CD34+ fraction and the CD34- fraction (page 2188 under the heading of “Preparation of CD34+ and CD34- fractions”) meets the limitation of claim 20 requiring one or more pretreatment steps prior to determining the amount of cancer stem cells in the sample. Terpstra et al teach that the late CAFCs of the AML sample are cells with long-term growth capacity (page 2193, lines 19-21). Terpstra et al conclude that late appearing CAFCs are due to highly immature cell present in the AML sample (page 2193, lines 28-29). The disclosure of the CAFC assay of AML cells also meets the limitations of claim 15 in addition to claim 14, because the CAFC assay is an in vitro culture.
Terpstra et al teach a method wherein SCID mice were transplanted with 7.5 X 106 or 1 X 106 cells of unseparated AML cells, CD34+AML cells or CD34- AML cells from the same AML sample (page 2189, under the heading of “AML growth in SCID mice” and Table 1). Terpstra et al teach that a cell dose titration ranging from 0.33 X 106 to 30 X 106 of unseparated AML cells showed a dose effect relationship between the cell dose and engraftment of AML (Table 2). Terpstra et al teach that each percentage in Table 2 represents one SCID mouse (legend for Table 2). Terpstra et al teach that the leukemic origin of the cells expanding in SCID mice was confirmed by morphological examination and by the leukemic immunophenotype (page 2192, first column, lines 10-13) in addition to the observation that the proliferation of the AML cells in the SCID mice was observed in the absence of exogenous hematopoietic growth factor, which are known to be required for expansion of normal bone marrow in SCID mice (page 2192, bridging sentence between the first and second paragraphs). Terpstra et al teach that the capacity to induce long-term growth is generally accepted as the parameter of choice for immaturity (page 2193, lines 30-31) and that both subsets as well as the unseparated AML cells contained immature progenitors with the capacity to initiate long-term AML growth as identified in vivo (page 2193, final paragraph). Terpstra et al teach that the CD34- fraction was capable of maintaining AML growth for more than 3 months and was also able to initiate renewed proliferation of AML after transfer to a second recipient (page 2191, under “Discussion” and Table 4). Thus, the number of colonies obtained after recovery from SCID mice at 106 days in Table 4 is indicative of an immature leukemic cell such as a leukemic stem cell) meeting the limitation of using a cobblestone assay to determine the amount of cancer stem cells in the AML sample.
It would have been prima facie obvious at the time that the claimed invention was made to use the cobblestone assay for quantitation of hematopoietic cancer stem cells. One of skill in the art would have been motivated to do so because Terpstra used this method for quantitation of AML stem cells.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 61, 62, 64, 65, 67, 71, 72, 76, 78 and 79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 62-77 and 81 of copending Application No. 17/881,007(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the application either anticipate or render obvious the instant claims.
Claim 81 anticipates instant claim 61, wherein the therapy is Il-13Rα2-based and bevacizumab-based, wherein the comparison of Il-13Rα2 expressing cancer cells before and after the therapy to determine if the amount of Il-13Rα2 expressing cancer cells after therapy is less than the amount of Il-13Rα2 expressing cancer cells before the therapy is equivalent to the determination in part (iii) of instant claim 61.
Claim 66 of the ‘007 application meets the limitations of instant claim 61, sections i) and ii) as well as “biological therapy” in instant claim 79. Claim 63 meets the limitation of instant claim 76. Claim 64 meets the same limitations as instant claim 63. Claim 65 meets the limitation of instant claim 72. Claims 74, 75 and 78 meets the limitation of brain cancer in instant claim 78.
The determination that the amount of Il-13Rα2 expressing cancer cells is reduced after therapy relative to pre-therapy levels in claim 66 renders obvious instant claim 61(ii) indicative that the Il-13Rα2 peptide and bevacizumab has anti-cancer stem cell activity.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643