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
Claims 13-16, 18-21 and 23-27 are pending in the Claim Set filed 9/03/2025.
Claims 13, 18-20 and 23 have been amended.
Applicants’ elected species: condition: cancer- leukemia, in the response filed 2/28/2025 to requirement for restriction.
Herein, claims 13-16, 18-21 and 23-27 are for examination to the extent that they read on the elected species.
Withdrawn Objections/Rejections
The objection to the Abstract is withdrawn.
The rejection of claims 13-27 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating colorectal cancer, does not reasonably provide enablement for the prevention of colorectal cancer or inhibition of cancer metastasis is withdrawn in view of the claim amendments.
The rejection of claims 13-27 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention is withdrawn in view of the claim amendments.
The rejection of claims 17 and 22 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn because calims 17 and 22 have been cancelled.
Maintained Rejections
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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
nonobviousness.
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).
The rejection of claims 13-15, 20 and 25-27 under 35 U.S.C. 103(a) as being unpatentable over Abulkalam et al (Minireview IP6: A novel Anticancer Agent p.343, 1997, cited in IDS filed 7/28/2023) [Abulkalam] in view of Tsien et al (USP 5866548, cited in IDS filed 7/28/2023) [Tsien] and Deliliers et al (Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells, British Journal of Haematology, p.577, 2002, Nov) [Deliliers]. Is maintained.
Regarding claims 13-15 and 20,
Abulkalam teaches a method of cancer inhibition by Inositol Hexaphosphate (IP6) and Inositol (Title). Abulkalam teaches that a striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP1-5, and inhibit cell growth. There is additional evidence that inositol (Ins) alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6 (Abstract; See entire document).
Abulkalam teaches that pilot studies of the absorption of lnsP6 by malignant cells in vitro in our laboratory also demonstrate that the cells almost instantaneously begin to accumulate InsP6 intracellularly, the rate of accumulation varying for the different types of cells. The ability and the rate at which the cells metabolized InsP6 also varied; YAC- I and K-562 cells contained only the lower InsP5, whereas HT-29 human colon carcinoma cells had Ins and InsP1-6. Interestingly, the normal growth rate of these cells is also different, HT-29 being the slowest and the other two, fast. Abulkalam teaches that it is possible that the turnover of InsP6 and the growth rate of the cells are intimately related (p.349, second paragraph). It would be obvious to those skilled in the art that Abulkalam teaches Inositol hexaphosphate (lnsP6 or IP6) as a laboratory agent. Thus, Abulkalam teaches using IP6 as a laboratory agent. Further, Abulkalam teaches that based on the available data, it is safe to say that a central pathway of InsP6 action is via control of cell division (p.349, fourth paragraph). Abulkalam teaches that by competing with IGF-II for receptor binding, InsP6 may short-circuit the autocrine IGF-11 loop, thereby reducing cellular proliferation (p.350, third paragraph). Finally, Abulkalam teaches that there are multiple beneficial actions of lnsP6, such as a differentiating and anti-neoplastic agent and that there are potential for many others (p.352, See Final Comments, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide Inositol Hexaphosphate (IP6) in a method of treating a disease condition, such as cancer (leukemia), comprising administering to a target in need thereof and/or imparting to target in need thereof an activity comprising cancer metastasis (i.e., in a patient in need thereof) having a reasonable expectation of success, since Inositol hexaphosphate (lnsP6 or IP6) was shown in studies as a laboratory agent to provide anti-cancer action as taught by Abulkalam.
Abulkalam differs from the claims in that the document does not teach butyryloxymethyl esters of Inositol hexaphosphate, i.e., Pro-IP6 (myo-inositol hexaphosphate dodeca kis(buty1yloxymethyl) ester) and that this phytic acid ester is provided in a method to treat a disease condition, such as, cancer (Leukemia).
However, Tsien and Deliliers, as a whole, cure the deficiencies.
Tsien teaches esterification of the inositol phosphates using butyryloxymethyl groups to produce butyryloxymethyl esters of inositol phosphate (IP6), (See, for example: See Abstract; col.3, lns.33-63; col.12, 27-48; where A1 to A6 = phosphoester, R’ is H and R is 3 carbon atoms, See below):
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wherein the butyryloxymethyl esters of inositol phosphate provide enhanced cell permeability rates while being amenable to intracellular cleavage to form the active inositol phosphate (i.e., IP6) (col.2, lns.54-64; col.3, lns.33-63; col.12, lns.18-26). Tsien teaches that it is preferred that all of phosphate groups be masked as propionyloxymethyl or butyryloxymethyl esters (col.4, lns.53-55), wherein the butyryloxymethyl esters are more potent (col.15, lns.15-17; Fig.9). Moreover, Tsien teaches that butyryl groups were found to provide optimum masking while still being easily cleaved by cell enzymes, i.e., hydrolysis (col.3, lns.1-9; col.10, lns.60-67; See entire document). Tsien teaches that once inside the cell, the ester derivative undergoes enzymatic hydrolysis and conversion back to the biologically active form of the second messenger, e.g., inositol phosphate (Abstract; col.1, lns.50-56; col.10, lns.60-67; col.15, lns.46-50; See entire document). Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide phytic acid butyryloxymethyl ester, wherein all of the phosphate of IP6 are masked (functionalized) with the substituent butyryloxymethyl, as instantly claimed. Furthermore, Tsien teaches that there is a need to provide a procedure for increasing the membrane permeability of second messengers, e.g., inositol phosphates, so that they can be introduced effectively into cells in amounts which are useful for investigational or therapeutic purposes (col.1, lns.12-20; col.2, lns.29-52).
Deliliers teaches the effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells (title). Deliliers teaches human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP6 had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. Moreover, Deliliers teaches that IP6 treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte–macrophage colony-forming unit (CFU-GM) formation (P ¼ 0Æ0062) in comparison to normal bone marrow specimens, which were not affected. Deliliers teaches our results confirm the antiproliferative activity of IP6 and that have a specific antitumour effect also in chronic myeloid leukaemias (Abstract; See entire document).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Inositol hexaphosphate (lnsP6 or IP6) as taught by Abulkalam in view of Tsien to provide butyryloxymethyl esters of inositol phosphate (IP6). One skilled in the art would have been motivated to do so because the IP6 butyryloxymethyl ester (phytic acid ester of Formula I, as claimed) would be expected to provide an increase in cell permeability while still amenable to intracellular cleavage, i.e., hydrolyzed at least one of inositol butyryloxymethyl ester substituents to a hydrogen), to form the active inositol phosphate (IP6) having anti-cancer action (as described above). Furthermore, it would have been prima facie obvious to provide butyryloxymethyl esters of Inositol hexaphosphate, i.e., Pro-IP6 (myo-inositol hexaphosphate dodeca kis(buty1yloxymethyl) ester, as claimed) in a method of treating a condition that is cancer (Leukemia) in view of Deliliers. One skilled in the art would have been motivated to do so because inositol phosphate (IP6) has the antiproliferative activity of IP6 was demonstrated to provide a specific antitumour effect in chronic myeloid leukaemias as taught by Deliliers.
Regarding claims 25-27,
Abulkalam teaches hexaphosphate inositol (IP6) is a broad-spectrum antineoplastic agent, wherein IP6 inhibited the growth of human leukemic hematopoietic cells, wherein the leukemic cell lines are highly susceptible to IP6 (p.3779, right col.). Additionally, the butyryloxymethyl esters of inositol phosphate provide enhanced cell permeability rates while being amenable to intracellular cleavage to form the active inositol phosphate (IP6). Further, Deliliers teaches hexaphosphate (IP6) provided a dose- dependent effect on human normal and leukaemic haematopoietic cells.In particular, Deliliers teaches our results confirm the antiproliferative activity of IP6 and that have a specific antitumour effect also in chronic myeloid leukaemias. Furthermore, the compound of butyryloxymethyl esters of inositol phosphate as taught by Abulkalam and Tsien, as a whole, is identical to the compound of Formula I, as instantly claimed. Thus, it would have been prima facie obvious to provide a composition comprising the butyryloxymethyl esters of inositol phosphate in a method of imparting, to a target in need thereof, an activity directed to the treatment of cancer (leukemia) comprising cancer metastasis inhibition having a reasonable expectation of success. Moreover, the butyryloxymethyl esters of inositol phosphate as taught by Abulkalam and Tsien, as a whole, is identical to the claimed compound of Formula I, so that it would necessarily follow that this compound would improve the activity by about 3% or more (Instant Claim 25); improve the activity by about 10% or more (Instant Claim 26); and, improve the activity by about 20% or more (Instant Claim 27) in a method of imparting an activity comprising cancer metastasis inhibition directed to the treatment of cancer (Leukemia), because the property would be the natural result of the combination of elements disclosed by the prior art. PAR Pharm., Inc. v. TWI Pharms, Inc., 773 F, 3d 1186, 1196 (Fed. Cir. 2014). Therefore, the effects observed by Applicant would have been latent to the method of the prior art. See MPEP 2145 II: Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). The fact that applicants have recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide butyryloxymethyl esters of Inositol Hexaphosphate (IP6) (compound that is identical to the claimed compound of Formula I) in a method of treating a disease condition, such as cancer (leukemia), comprising administering to a target in need thereof and/or imparting to target in need thereof an activity comprising cancer metastasis (e.g., in a patient in need thereof) having a reasonable expectation of success, in view of the teachings of Abulkalam, Tsien and Deliliers, as a whole.
All the claimed elements herein are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious for one of ordinary skill in the art to provide instantly claimed invention and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by Abulkalam, Tsien and Deliliers, as a whole.
Claims 16, 18, 19, 21, 23 and 24 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Abulkalam et al (Minireview IP6: A novel Anticancer Agent p.343, 1997, cited in IDS filed 7/28/2023) [Abulkalam] in view of Tsien et al (USP 5866548, cited in IDS filed 7/28/2023) [Tsien] and Deliliers et al (Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells, British Journal of Haematology, p.577, 2002, Nov) [Deliliers]. as applied to claims 13-15, 17, 20 and 22 above and further in view of Nicolau et al (EP1973398) { Nicolau].
The teachings of Abulkalam, Tsien and Deliliers are described above.
Abulkalam, Tsien and Deliliers differ from the claims in that the document do not teach the route of administration, dosage amounts of a phytic acid easter: butyryloxymethyl esters of Inositol hexaphosphate, i.e., Pro-IP6 (myo-inositol hexaphosphate dodeca kis(buty1yloxymethyl) ester.
However, Nicolau cures the deficiencies.
Nicolau teaches inositol tripyrophosaphate (ITPP) (i.e., derivative of IP6) for treating a disease comprising cancers that include breast cancer, colon cancer, lung cancer, cervical cancer and leukemia or multiple myeloma and tumor metastasis (Abstract; [0001]; [0032]; [0042]; Figure 1; See entire document). Further, Nicolau teaches inositol hexaphosphate (IHP) is unable to pass through the mammalian erythrocyte membrane, it is capable of combining with hemoglobin of mammalian red blood cells at the binding site of DPG to modify the allosteric conformation of hemoglobin, the effect of which is to reduce the affinity of hemoglobin for oxygen [0014]. Nicolau teaches that tumor growth is angiogenesis dependence, wherein angiogenesis has been associated with cancers, e.g., leukemia tumors ([0031-0032]). Nicolau teaches inositol tripyrophosaphate (ITPP) (i.e., a derivative of inositol hexaphosphate) is provided for the treatment of conditions associated with accelerated cell division [0065].
Furthermore, Nicolau ITPP formulations (i.e., compositions containing a derivative of IP6) are administered orally and parenterally comprising transdermal, intraperitoneal and intravenously, wherein the dosage of the composition will depend on the condition being treated, the particular derivative used, and other clinical factors such as weight and condition of the patient and the route of administration of the compound. However, for oral administration, a recommended dosage is in the range of 0.1 to 5.0 g/kg/day (i.e., 0.1 g = 100 mg/kg/day) [0070-0073], of which overlaps with the claimed amount (Instant Claims 18, 19, 23 and 24). In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257,191 USPQ 90 (CCPA 1976); In re Woodruff, 91 9 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. One skilled in the art would have recognized that ITPP is a phytic acid phosphate derivative of IP6 (inositol phosphate) that is structurally similar to the inositol phosphate (IP6) as taught by Abulkalam, Tsien and Deliliers, as a whole (described above). A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities, as is the case here. An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties. In rePayne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In rePapesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990). Thus, it would have been well within the purview of one of ordinary skill in art to follow the guidance provided by Nicolau in order to optimize the delivery of myo-inositol hexaphosphate dodeca kis(butylyloxymethyl) ester (i.e., identical compound of claimed Formula I) to a target in need thereof, wherein the butylyloxymethyl phytic acid derivative is provided in method of treating cancer (Leukemia) comprising orally administering from about 100 mg/ kg/day to a target in need thereof having a reasonable expectation of success. Optimization of parameters is a routine practice that would be obvious to a person of ordinary skill in the art to employ and reasonably expect success. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955) & MPEP 2144.05. Moreover, the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to determine the optimal amounts of butylyloxymethyl phytic acid derivative achieve an effective amount the compound. Therefore, it would have been obvious for one of ordinary skill in the art to provide instantly claimed invention and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by Abulkalam, Tsien, Deliliers and Nicolau, as a whole.
Response to Arguments
Applicants argue that the compound of Formula I is hydrolyzed in a living body to provide butyric acid in addition to IP6. Butyric acid could activate G protein-coupled receptor 41 (GRP41), a short chain fatty acid receptor, to increase energy expenditure and to ameliorate diabetes. (See Kimura et al. PNAS, 2011 and Heidor et al., Current Drug Targets, 2012; cited in the IDS filed on 7/28/2023). The present application discloses that the released "butyric acid" surprisingly has the anti-diabetes effect (controlling of body energy expenditure) and the anti-cancer effect in addition to the effect of IP6. Further, the compound of Formula I has a) improved bioavailability and b) pharmacological effect because of butyric acid as utilized in the present application.
However, the Examiner would like to point out that Applicants’ species election without traverse of a condition: cancer- leukemia, in the response filed 2/28/2025 to requirement for restriction filed 1/03/2025 (shown below):
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Therefore, Instant Claims are examined to the extent that they reach on the elected species: condition: leukemia.
The Examiner would like to point out that although, the condition: diabetes, is recited in Instant Claims in claim 14, Applicants’ species election without traverse of a condition: cancer- leukemia, is herein maintained. So that Instant Claims are examined to the extent that they read on the elected species, condition: cancer- leukemia.
MPEP 819 Office Generally Does Not Permit Shift:
The general policy of the Office is that applicants are not permitted to shift to claim another invention after an election is made and an Office action on the merits is made on the elected invention. Specifically, the applicant may not disaffirm or change their election, as a matter of right, after making an oral election and receiving an Office action based upon that oral election in a pending application.
Additionally, the compound ‘butyric acid’ is not recited in Instant claims.
Furthermore, the Examiner would like to point out that after complete search of the Specification, Applicants statement: The present application discloses that the released "butyric acid" surprisingly has the anti-diabetes effect (controlling of body energy expenditure) and the anti-cancer effect in addition to the effect of IP6. Further, the compound of Formula I has a) improved bioavailability and b) pharmacological effect because of butyric acid as utilized in the present application, is not disclosed in the Specification.
Specification at para. [0083] states:
[0083] "Diabetes" is a disease referring to a state where blood glucose level or hemoglobin Ale value exceeds a prescribed reference, it is classified into type I diabetes, type 2 diabetes, diabetes caused by a genetic abnormality such as maturity-onset diabetes of the young), secondary diabetes, gestational diabetes, and the like.
MPEP 714.02 and 2163.06 states: Applicant should specifically point out the support for any amendments made to the disclosure.
Applicants argue that Abulkalam differs from the claims in that the document does not teach butyryloxymethyl esters of Inositol hexaphosphate, i.e., Pro-IP6 (myoinositol hexaphosphate dodecakis(butylyloxymethyl) ester) and that this phytic acid ester is provided in a method to treat a disease condition, such as, cancer (Leukemia). The Office Action opines that Tsien and Deliliers, as a whole, cure the deficiencies of Abulkalam.
Applicants argue that Tsien is generally directed to compositions and methods are provided for increasing the permeability of phosphate-containing second messengers into a cell without disrupting the cell membrane. Tsien discloses that the replacement of acetoxymethyl groups with propionyloxymethyl and butyryloxymethyl groups produces inositol phosphate esters (i.e., IP6) which have much greater cell permeability rates while still being amenable to intracellular cleavage to form the active inositol phosphate.
Applicants argue that the Office Action erroneously asserts that "It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Inositol hexaphosphate (lnsP6 or IP6) as taught by Abulkalam in view of Tsien to provide butyryloxymethyl esters of inositol phosphate (IP6). One skilled in the art would have been motivated to do so because the IP6 butyryloxymethyl ester (phytic acid ester of Formula I, as claimed) would be expected to provide an increase in cell permeability while still amenable to intracellular cleavage, i.e., hydrolyzed at least one of inositol butyryloxymethyl esters substituents to a hydrogen, to form the active inositol phosphate (IP6) having anti-cancer action. Applicants argue that Tsien fails to disclose or suggest the pharmacological effects of butyric acid in a method for treating a disease or a method for imparting, to a patient in need thereof, an activity, as set forth in amended independent claims 13 and 20.
Further, Applicants argue that Deliliers is generally directed to the effects of pharmacological IP6 doses on the growth and cell cycle of various human leukemic cell lines, and of fresh normal and chronic myelogenous leukemia human bone marrow progenitor cells. For instance, Deliliers discloses that the spectrum of neoplasia on which IP6 has anti proliferative activity could be extended to acute and chronic myeloid leukemias.
Applicants argue that the Office Action erroneously asserts that "One skilled in the art would have been motivated to do so because inositol phosphate (IP6) has the antiproliferative activity of IP6 was demonstrated to provide a specific anti-tumour effect in chronic myeloid leukaemias as taught by Deliliers." Contrary to the Office Action's assertion, a skilled artisan would readily understand that one cannot predict or expect a specific anti-tumour effect in chronic myeloid leukaemia taught by Deliliers to extend to other diseases or conditions. As such, Applicants argue that Deliliers fails to disclose or suggest the pharmacological effects of butyric acid in a method for treating a disease or a method for imparting, to a patient in need thereof, an activity, as set forth in amended independent claims 13 and 20.
The Examiner would like to point out that although, the condition: diabetes, is recited in Instant Claims in claim 14, Applicants’ species election without traverse of a condition: cancer- leukemia, in the response filed 2/28/2025 to requirement for restriction filed 1/03/2025. So that Instant Claims are examined to the extent that they read on the elected species, condition: cancer- leukemia.
MPEP 819 Office Generally Does Not Permit Shift:
The general policy of the Office is that applicants are not permitted to shift to claim another invention after an election is made and an Office action on the merits is made on the elected invention. Specifically, the applicant may not disaffirm or change their election, as a matter of right, after making an oral election and receiving an Office action based upon that oral election in a pending application.
Additionally, the compound ‘butyric acid’ is not recited in Instant claims.
Moreover, although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181,26 USPQ2d 1057 (Fed. Cir. 1993).
Herein, Instant Claims are examined to the extent that they read on the elected species, condition: cancer- leukemia.
Applicants’ arguments have been fully considered but they are not persuasive, because instant claims are directed to a method for treating a disease: elected species, condition: cancer- leukemia, comprising, administering to a patient in need thereof an effective amount of a compound, or its pharmaceutically acceptable salt, of Formula 1. Furthermore, the compound butyric acid (i.e., produced by the hydrolysis of butyryloxymethyl esters of inositol phosphate) is not recited in instant claims.
Moreover, it would have been obvious to one skilled in the art to provide butyryloxymethyl esters of inositol phosphate in view of the teachings of Abulkalam, Tsien and Deliliers, as a whole. Especially, since Abulkalam teaches that Inositol Hexaphosphate (IP6) and Inositol (Title) have been demonstrated to provide anti-cancer action both in vivo and in vitro. Moreover, Tsien teaches esterification of the inositol phosphates using butyryloxymethyl groups to produce butyryloxymethyl esters of inositol phosphate (IP6), wherein Tsien teaches that it is preferred that all of phosphate groups be masked as propionyloxymethyl or butyryloxymethyl esters (col.4, lns.53-55), and the butyryloxymethyl esters are more potent, wherein Tsien teaches that butyryl groups provide optimum masking while still being easily cleaved by cell enzymes, i.e., hydrolysis. Particularly, Tsien teaches that once inside the cell, the ester derivative undergoes enzymatic hydrolysis and conversion back to the biologically active form of the second messenger, e.g., inositol phosphate, i.e., IP6. Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide phytic acid butyryloxymethyl ester, wherein all of the phosphate of IP6 are masked (functionalized) with the substituent butyryloxymethyl, as instantly claimed. Furthermore, Tsien teaches that there is a need to provide a procedure for increasing the membrane permeability of second messengers, e.g., inositol phosphates, so that they can be introduced effectively into cells in amounts which are useful for investigational or therapeutic purposes. In view of Abulkalam teaching that Inositol Hexaphosphate (IP6) and Inositol (Title) both provide anti-cancer action both in vivo and in vitro. Along these lines, Abulkalam further teaches that there are multiple beneficial actions of lnsP6 (i.e., IP6) such as being an anti-neoplastic agent and that there are potential for many others properties thereof.
Deliliers teaches the effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells (title). Deliliers teaches. IP6 has a dose-dependent cytotoxic effect on all of the evaluated cell lines,wherein IP6 treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte–macrophage colony-forming unit (CFU-GM) formation (P ¼ 0Æ0062) in comparison to normal bone marrow specimens, which were not affected. Moreover, Deliliers teaches our results confirm the antiproliferative activity of IP6 and that have a specific anti-tumour effect also in chronic myeloid leukaemias.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide butyryloxymethyl esters of inositol phosphate in a method of treating a disease condition, such as cancer (leukemia), comprising administering to a target in need thereof and/or imparting to target in need thereof an activity comprising cancer metastasis since butyryloxymethyl esters of inositol phosphate is known be hydrolyzed to IP6 having a reasonable expectation of success. According to MPEP § 2144, IV. Rationale Different from Applicant's is Permissible: The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (In re Kahn, 78 USPQ2d 1329, 1336, Federal Circuit 2006).
Applicants argue that Tsien fails to disclose the pharmacological effects of butyric acid in a method for treating a disease or a method for imparting, to a patient in need thereof, an activity, as set forth in amended independent claims 13 and 20. However, the compound butyric acid is not recited in instant claims (emphasis added). Also, Applicants argue that Deliliers fails to disclose the pharmacological effects of butyric acid in a method for treating a disease or a method for imparting, to a patient in need thereof, an activity, as set forth in amended independent claims 13 and
Applicant’s arguments have been fully considered but they are not persuasive, because butyryloxymethyl esters of inositol phosphate as taught by Tien is structurally indistinguishable from the claimed compound of Formula 1, i.e., butyryloxymethyl esters of inositol phosphate as taught by Tien is the identical compound as instantly claimed, so that it would necessarily follow that the hydrolysis of butyryloxymethyl esters of inositol phosphate in a living body would provide butyric acid in addition to IP6. The production of butyric acid would be the natural result of the combination of the prior art elements. Thus, the formation of butyric acid would necessarily follow when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578,581 (CCPA 1981)). References are evaluated by what they suggest to one versed in the art, rather than by their specific disclosures. In re Bozek, 163 USPQ 545 (CCPA 1969). Moreover, it would necessarily follow that butyryloxymethyl esters of inositol phosphate as taught by Tien would provide treatment for a condition: diabetes, having a reasonable expectation of success.
In addition, Deliliers explicitly teaches our results confirm the antiproliferative activity of IP6 and that have a specific anti-tumour effect also in chronic myeloid leukaemias (i.e., myeloid leukaemias are a form of leukemia).
The test for obviousness is not whether the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Moreover, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). The fact that Applicants have recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant is reminded that obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). In the instant case, Applicants have failed to provide evidence showing there was no reasonable expectation of success.
Conclusions
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/THURMAN WHEELER/ Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619