DETAILED ACTION
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 .
Claims 1, 5, 6, 8, 24, 27, 33, 38, 40, 41, 46, 50, 51, 53, 54, 56, 59, 63-65, 69, 70, 83, 86, 92, 97, 100, 104, 105, 107, 108, 110, 113, 118 and 119 are pending in this application.
Claim Rejections - 35 USC § 112
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.
Claims 1, 5, 6, 8, 24, 27, 33, 38, 40, 41, 46, 50, 51, 53, 54, 56, 59, 63-65, 69, 70, 83, 86, 92, 97, 100, 104, 105, 107, 108, 110, 113, 118 and 119HIF1- are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, does not reasonably provide enablement for the full breadth of the claims encompassing to a method of treating pancreatic steatosis, pancreatic cancer, non-alcoholic fatty liver disease, or hepatocellular carcinoma in a subject in need thereof comprising: (a) administering an effective amount of a HIF1-α Pathway Inhibitor and an PFKFB3 inhibitor to the subject; (b) administering an effective amount of a HIF1-α Pathway Inhibitor to the subject, wherein the subject has previously been administered a PFKFB3 Inhibitor; or (c) administering an effective amount of a PFKFB3 Inhibitor to the subject, wherein the subject has previously been administered a HIF1-α Pathway Inhibitor; wherein the PFKFB3 inhibitor does not inhibit PI3K/AKT/mTOR pathway or HIF1-α. 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, 5) existence of working samples, 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).
(1) The nature of the invention, (6) Breadth of the claims and (8) Undue experimentation.
The nature of the invention is to a method of treating pancreatic steatosis, pancreatic cancer, non-alcoholic fatty liver disease or hepatocellular carcinoma in a subject in need thereof comprising: (a) administering an effective amount of a HIF1-α Pathway Inhibitor and an PFKFB3 inhibitor to the subject; (b) administering an effective amount of a HIF1-α Pathway Inhibitor to the subject, wherein the subject has previously been administered a PFKFB3 Inhibitor; or (c) administering an effective amount of a PFKFB3 Inhibitor to the subject, wherein the subject has previously been administered a HIF1-α Pathway Inhibitor; wherein the PFKFB3 inhibitor does not inhibit PI3K/AKT/mTOR pathway or HIF1-α.
Claims 8, 33, 40, 41, 69, 70, 83 and 92 limit the pancreatic steatosis is associated with infiltration of fat in the pancreas, infiltration of fat in the pancreas with pancreatic inflammation, infiltration of fat in the pancreas with development of pancreatic fibrosis, pancreatic cancer, exocrine pancreatic cancer, neuroendocrine pancreatic cancer, adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, colloid carcinoma, ductal adenocarcinoma (PDAC).
Claims 46, 50, 51, 53, 54, 100, 104, 105, 107 and 108 limit the HIF1-α Pathway Inhibitor and PFKFB3 inhibitor to wherein the administered HIF1-α Pathway Inhibitor is silibinin, PX-478 or YC-1, or a salt thereof; ganetespib (ST-9090), phenethyl isothocyanate, or BAY-87-2243, or a salt thereof: or a HIF1-α Inhibitor; wherein the administered HIF1-α Inhibitor is antisense oligonucleotide EZN-2968 or nanobody AG-1, AG-2, AG-3, AG-4, AG-5, VH H212, or AHPC; wherein the administered HIF1-α Pathway Inhibitor and/or PFKFB3 Inhibitor is an antibody or antigen- binding antibody fragment (single chain antibody, a single-domain antibody, a Fab fragment, F(ab')2 fragment, Fd fragment; Fv fragment, scFv, dAb fragment, or another engineered molecule, such as a diabody, triabody, tetrabody, minibody, and a minimal recognition unit), a nucleic acid molecule (an aptamer, antisense molecule, ribozyme, MiRNA, dsRNA, ssRNA, and shRNA), a peptibody, a nanobody, a HIF1-α Pathway member binding polypeptide, a PFKFB3 binding polypeptide, a small molecule HIF1-α Pathway inhibitor, or a small molecule PFKFB3 Inhibitor; wherein the administered PFKFB3 Inhibitor: (a) is KAN0436151 or KAN0436067, or a salt thereof; (b) has the structure of formula 1-53 or 54, PQP, N4A, YN1, PK15, PFK-158, YZ29, Compound 26 (AZ26), KAN0436151, KAN0436067, or BrAcNHErOP, depicted in FIG. 1A-1C or 1D, or a salt thereof; (c) has the structure of formula AZ44-AZ70 or AZ71, depicted in FIG. 1 E, or a salt thereof; or (d) is AZ67, or a salt thereof; wherein the HIF1-α Pathway Inhibitor and the PFKFB3 inhibitor are co- administered to the subject, or wherein the administration of the HIF1-α Pathway Inhibitor and/or the PFKFB3 inhibitor administration is oral, parenteral, orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal, intranasal, intratumoral, or intravenous.
HIF1-α Pathway Inhibitor – Acriflavin, Aminoflavone, Andrographolide, Anthracyclines, Apigenin, 5-Azacitidine, BAY 87-2243, Bavachinin, Bortezomib, Camptothecin, Cardenolides, CAY10585, Celastrol, Chetomin, Curcumin, Danuorubicin, Diallyl trisulfide (DATS), Digoxin, DIM (3,3’-diindolylmethane), Doxorubicin, Echinomycin, Emodin, ENDM-1198, ENMD-1200, ENMD-1237, Everolimus, EZN-2208, EZN-2698, EZN-2968, GA, Ganetespib (ST-9090), GAs, Gliotoxin, Herboxidiene (GEX1A), IDF-11774, Irinotecan, Isoliquiritigen (ILTG), KF58333, LW6, LY294002, Mitioxantrone, Mycophenolate mofetil, Niclosamide, Ouabain, PEITC, Phenethyl isothocyanate, PI-103, PP-242, Proscillaridin, Pseudolaric acid B (PAB), PX-478, Radicicol, Romidepsin, SCH6636, Selumetinib, Silibinin, Sirolimus, SN38, Sulforaphane, Sunitinib, Temsirolimus, Thymoquinone, Topotecan, Trametinib, Trichostatin, Wondonin, Wortmannin, YC-1, 2ME2s, 2ME2, 17-AAG, 17AG, 17-DMAG, etc. Where those in bold indicates those HIF1-α Pathway Inhibitor which are described in the specification.
PFKFB3 Inhibitor – AZ26, AZ44-AZ70, AZ71, AZ-67, BrAcNHErOP, Cabozantinib S-malate, KANO0436151, KANO0436067, KANO438757, Lomitapide, N4A, PFK15, PFK-158, PQP, YN1, YZ29, 3PO, etc. Where those in bold indicates those HIF1-α Pathway Inhibitor which are described in the specification.
Therefore, the nature of the invention is a chemical case, wherein there is natural unpredictability in performance of certain species or sub-combinations other than those specifically enumerated; See MPEP 2163. Accordingly, it is the Office's position that undue experimentation would be required to make and use the HIF1-α Pathway Inhibitor and an PFKFB3 inhibitor, with a reasonable expectation of success, because it would not be predictable from the disclosure of any particular species what other species may or may not work; See MPEP 2164.03.
The claims broadly encompass a genus of agents that are described solely in terms of their function of treating pancreatic steatosis, pancreatic cancer, non-alcoholic fatty liver disease, or hepatocellular carcinoma. The specification teaches PFKFB3 inhibitor inhibits the expression of PFKFB3 and the ability of compound to inhibit PFKFB3 activity are known in the art (paragraph 50). The specification provides example of coding sequence of human PFKFB3 (paragraph 53). The specification states the therapeutic nucleic acids that inhibit PFKFB3 activity can routinely be designed and prepared based on each of the provided human PFKFB3 transcript sequence using methods known in the art (paragraph 53). The specification provides various example of PFKFB3 that can administered (paragraph 60-70). The specification teaches HIF1-α pathway inhibitor refers to a composition that inhibits or reduces HIF1-α directly or indirectly (paragraph 73). The specification teaches various examples of a HIF1-α inhibitor (paragraph 81-87). The specification teaches multiple HIF1-α coding sequences to provide "representative examples" (paragraph 88). Thus, the claims are broad generic claims based on the generically claimed HIF1-α Pathway Inhibitor and an PFKFB3 inhibitor, which can be any number of agents of varying chemical and biological genera, and the generically recited term " HIF1-α Pathway Inhibitor and an PFKFB3 inhibitor" which encompasses exerting an effect on any number of cells to provide treatment to a generic subject having any number of diseases.
Thus, given the broadest reasonable interpretation, the claims encompass any agent that is an inhibitor of the HIF1-α Pathway and an PFKFB3 pathway. These agents have the function of modulating HIF1-α and PFKFB3, which broadly includes decreasing HIF1-α and PFKFB3 expression treating pancreatic steatosis, pancreatic cancer, non-alcoholic fatty liver disease, or hepatocellular carcinoma .
(2) The state of the prior art and (4) The predictability or unpredictability of the art.
The instant specification and claims teach that the HIF1-α pathway inhibitor and PFKFB3 inhibitor is an antibody, antigen binding fragment, nucleic acid molecule, a peptibody, a nanobody, a polypeptide, a small molecule or a salt thereof. The instant claims thereby encompass many genera of chemical and biological molecules, without any described structure that is required for the molecules to perform the required functions.
Regarding the encompassed proteins, protein chemistry is one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. An amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all. The sensitivity of proteins to alterations of even a single amino acid in a sequence, the replacement of a single lysine resides at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein, that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen.
The pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate. One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered. Conclusions from the comparison analysis are often stretched with regard to protein products. Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable. Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality. As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search. Although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further. Given the knowledge of one skilled in the art the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function, the claimed proteins could not be predicted based on sequence identity.
Regarding the encompassed antibodies, the functional characteristics of antibodies, including binding specificity and affinity, are dictated on their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen- binding site. The art shows an unpredictable effect when making single versus multiple changes to any given CDR. The VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen V. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself even when preparation of such an antibody would be routine and conventional. Amgen, 872 F.3d at 1378-79. A key role played by the written description requirement is to prevent "attempts] to preempt the future before it has arrived." Ariad at 1353, (quoting Fiers V. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies. In the instant application, neither the art nor the specification provides a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Regarding small molecule inhibitors of a particular protein target, the prediction of binding to a target, much less the inhibitory activity, is highly unpredictable. Accurately predicting the binding affinity of new drug candidates remains a major challenge in drug discovery. There are a vast number of possible compounds that may function as an inhibitor of a cytokine or cytokine receptor, many of which have likely not been discovered. Relying on virtual screening also lends unpredictability to the art regarding identification of molecules that would be capable of the required functions of the instant claims. There are two main complex issues with predicting activity for a small molecule: accurate structural modeling and/or correct prediction of activity. Developing selective JAK inhibitors is difficult. Even when guided by structure, JAK structure-activity relationships have been challenging owing to the similarities of the enzymes. Therefore, it is impossible for one of skill in the art to predict that any particular encompassed small molecule therapeutic would function to inhibit a particular protein, or treat disease.
Regarding nucleic acid-based agents, the efficacy of any possible RNA interference therapeutic modality is highly unpredictable. This unpredictability stems from an inability to predict the effects of any particular sequence the expression or function of any target. The development of RNAi based therapeutics faces several challenges, including the need for controllable or moderate promoter systems and therapeutics that are efficient at low doses, the ability of an unpredictable number of sequences to stimulate immune responses, such as type I interferon responses, competition with cellular RNAi components, the side effect of suppressing off targets, and challenging delivery. The success of antisense strategies, including anti-RNA and anti-DNA strategies are also highly unpredictable. The efficacy of antisense effects varies between different targeted sites of RNA molecules and three-dimensional RNA structures, while DNA-targeting strategies have numerous problems including a restricted number of DNA sequences that can form triple helices at appropriate positions within genes and the inaccessibility of particular sequences due to histones and other proteins. The variation in RNA or DNA based therapeutics will often dramatically affect the biological activity and characteristics of the intended therapeutic. The claimed RNA and DNA therapeutics could not be predicted based on the targets selected or similarities to the disclosed example therapeutics. Therefore, it is impossible for one of skill in the art to predict that any particular encompassed RNA or DNA based therapeutic, such as RNAi molecules and antisense oligonucleotides, would function to decrease expression or function of a target gene or protein, or treat disease.
It is noted that KAN0438757, PX-478, YC-1, Ganetespib, and BAY 87-2243 are known in the art primarily as oncology therapeutics. The mere identification of these compounds by name, without any supporting disclosure demonstrating their utility in a cardiovascular context, does not establish the inventors possessed the claimed invention. A claimed specification that simply names compounds and asserts a new therapeutic use without evidentiary support does not show possession of that use across the full claimed scope. See Regents of the Univ. of Cal. V. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997). The state of the art further underscores this deficiency.
(5) The amount of direction or guidance provided by the invention; (7) The existence of working examples
The working examples demonstrate the chemical structures of the various claimed HIF1-a pathway inhibitors and PFKFB3 inhibitors. Thus, the guidance provided in the specification is limited to the chemical structures of claimed HIF1-α pathway inhibitors and PFKFB3 inhibitors. However, the guidance provided above does not provide adequate guidance to carry out the claimed method commensurate in scope with the claims, which broadly encompasses treating cardiovascular disease with HIF1-α pathway inhibitor and PFKFB3 inhibitor.
Applying the above test to the facts of record, it is determined that 1) no declaration under 37 C.F.R. 1.132 or other relevant evidence has been made of record establishing the amount of experimentation necessary, 2) insufficient direction or guidance is presented in the specification with respect to treating cardiovascular disease with HIF1-α pathway inhibitor and PFKFB3 inhibitor, 3) the relative skill of those in the art is commonly recognized as quite high (post-doctoral level). One of skill in the art would require guidance, in order to make or use the method of treating cardiovascular disease with HIF1-α pathway inhibitor and PFKFB3 inhibitor in a manner reasonable in correlation with the scope of the claims. Without proper guidance, the experimentation to is undue.
The Applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including treating cardiovascular disease with HIF1-α pathway inhibitor and PFKFB3 inhibitor. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ19 24 (CCPA 1970). Without such guidance, determining the method for treating cardiovascular disease with HIF1-α pathway inhibitor and PFKFB3 inhibitor, the specific modifying effect of with HIF1-a pathway inhibitor and PFKFB3 inhibitor and the subject in which the method is performed is unpredictable and the experimentation left those skilled in the art is unnecessarily and improperly, extensive and undue. See Amgen Inc V Chugai Pharmaceutical Co Ltd. 927 F 2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991) at 18 USPQ2d 1026- 1027 and Exparte Forman, 230 U.S.P.Q. 546(Bd. Pat=. App & int. 1986). Due to the extreme breadth of the claims, as written, the lack of guidance in the prior art, and the lack of guidance in the specification, one of ordinary skill in the art would have to engage in undue experimentation to make and use the invention of the claims, as written. In view of all of the above, the claimed invention does not satisfy the requirements of 35 U.S.C. 112 first paragraph.
Claims 64, 118 and 119 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In evaluating the enablement question, several factors are to be considered. In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988); Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed.
The method of treating pancreatic steatosis, pancreatic cancer, non-alcoholic fatty liver disease or hepatocellular carcinoma with the pharmaceutical compositions of the instant invention where an additional therapeutic agent is administered including any therapeutic agent, GPR81 inhibitors, etc. are included in the compositions. The specification does not define that which is intended in the additional therapeutic agent, GPR81 inhibitors, etc. Reserpine and 3-hydroxybutyrate (3-OBA) are known GPR81 inhibitors which are neither supported nor contemplated. The list of agents that fall under “therapeutic agent” is extensive of which there is no direction or teaching in the specification to the nature of these agents.
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 27, 46, 51, 53, 69, 83, 86, 100, 105, 107 and 113 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. The following reasons apply:
Regarding claim 27, the abbreviations "e.g." which mean "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 46 is vague and indefinite in that it is not known what is meant by the definition of HIF1-α Pathway Inhibitor which is defined as a HIF1-α Inhibitor.
Regarding claim 51, the abbreviations "e.g." which mean "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 51, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 53 recites "depicted in FIG. 1A-1C or 1D" and "depicted in FIG. 1E". Figures and drawings serve to illustrate the disclosure but are not substitute for clear claim language. Incorporating figures into claims by reference introduces ambiguity. MPEP 2173.05(s) states "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)."
Claim 53 is vague and indefinite in that it is not known what is meant by the list of PFKFB3 Inhibitors where KAN0436151, KAN0436067 and AZ67 are each listed twice.
Claim 53 is vague and indefinite in that it is not known what is meant by “formula 1-53 or 54”.
Regarding claim 69 and claims dependent thereon, the abbreviations "e.g." which mean "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 100 is vague and indefinite in that it is not known what is meant by the definition of HIF1-α Pathway Inhibitor which is defined as a HIF1-α Inhibitor.
Regarding claim 105, the abbreviations "e.g." which mean "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 105, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 107 recites "depicted in FIG. 1A-1C or 1D" and "depicted in FIG. 1E". Figures and drawings serve to illustrate the disclosure but are not substitute for clear claim language. Incorporating figures into claims by reference introduces ambiguity. MPEP 2173.05(s) states "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)."
Claim 107 is vague and indefinite in that it is not known what is meant by the list of PFKFB3 Inhibitors where KAN0436151, KAN0436067 and AZ67 are each listed twice.
Claim 107 is vague and indefinite in that it is not known what is meant by “formula 1-53 or 54”.
Regarding claim 113, the abbreviations "e.g." which mean "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
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, Jeffrey H. Murray can be reached on 571-272-9023. 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.
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
Prosecution Insights