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 .
Priority
This application is a national stage entry of PCT/US2021/045231 filed on 08/09/2021, which claims priority to U.S. Provisional Application No. 63/062,874 filed on 08/07/2020.
Response to Amendment
Applicant’s amendment filed on August 12, 2026 amending claim 20 and canceling claim 21 has been entered. Claims 11-19, 28 and 30 are withdrawn. Claims 20, 22-27 and 29 are currently presented for examination.
Response to Arguments
Applicant's arguments filed August 12, 2026 have been fully considered but they are not persuasive.
The replacement drawings submitted on August 12, 2026 are acknowledged. However, they are not sufficient to overcome the previous objections to the drawings. Even though the quality of the figures is improved, Figures 1-9 are still too small and illegible and moreover, the figures are now in color. Thus, the previous objection to the figures is maintained and has been modified in view of the replacement drawings filed on August 12, 2026.
With respect to the double patenting rejections, Applicant argues that claim 20, as amended, is patent eligible over copending '153 because the claims of copending '153 application do not teach or suggest a method of preventing or treating blood brain barrier (BBB) permeability in a subject, comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, wherein the subject has or is at risk of a neurodegenerative condition, disorder, or disease where BBB permeability occurs and the BBB permeability includes impaired BBB integrity and increased BBB vascular permeability. Applicant argues that the claims of copending '153 recite a method of treating Alzheimer's disease in a subject comprising administering a therapeutically effective amount of a 15-PGDH inhibitor, but is silent as to whether a 15-PGDH inhibitor could be used to treat or prevent BBB permeability in a subject and that when administered could protect and/or decrease BBB permeability in a subject as claimed.
Applicant argues that the same is true regarding the double patenting rejection over copending ‘153 in view of Wong et al.
These arguments are found not persuasive because the claims as amended claim a method for preventing or treating blood brain barrier (BBB) permeability in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a 15- PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, wherein the subject has or is at risk of a neurodegenerative condition, disorder, or disease where BBB permeability occurs and the BBB permeability includes impaired BBB integrity and increased BBB vascular permeability. The claims further recite that the subject is a subject having been identified as having Alzheimer’s disease. Thus the claims of the instant application are drawn to the treatment of a patient with Alzheimer’s disease comprising the administration of a 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject. Although copending ‘153 does not claim preventing or treating blood brain barrier permeability in the subject as claimed, or administering the 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, the method of copending ‘153 will inherently prevent or treat blood brain barrier permeability in said subject as claimed in the instant claims, since administering the same compound to the same patient population will inherently result in the same effect as claimed which is to prevent or treat BBB permeability. Moreover, administering the same 15-PGDH inhibitor as claimed will inherently protect the BBB and/or decrease BBB permeability in the subject as claimed in the instant claims.
It is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
In the instant case, the use of the claimed compound in treating Alzheimer’s disease is claimed in copending ‘153 and thus the effect or result of said method in treating or preventing blood brain barrier permeability is also inherently present in the method of the claims of copending ‘153. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999).
Thus the cited claims of the instant application would be anticipated over the cited claims of copending ‘153 and Applicant’s amendments to the claims do not overcome the rejection. Accordingly, for these reasons the previous double patenting rejections are hereby maintained and modified rejections in view of Applicant’s amendments to the claims are detailed below.
With respect to the rejection under 35 USC 102, Applicant argues claim 20, as amended, is not anticipated by Markowitz et al. because Markowitz et al. do not teach a method of preventing or treating blood brain barrier (BBB) permeability in a subject, comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, wherein the subject has or is at risk of a neurodegenerative condition, disorder, or disease where BBB permeability occurs and the BBB permeability includes impaired BBB integrity and increased BBB vascular permeability. Applicant argues that Markowitz et al. teaches a method of promoting neuroprotection in a subject from axonal degeneration, neuronal cell death, and/or glia cell death after injury, augment neuronal signaling underlying learning and memory, stimulate neuronal regeneration after injury, and/or treat diseases, disorders, and/or conditions of the nervous system by administering a 15-PGDH inhibitor to increase PGE2 levels in the nervous system/brain [0015]. Applicant argues that Markowitz et al. only showed that SW033291 could be used to promote neuroprotection following TBI, Paragraphs [0328-0330], that 15-PGDH activity decreased following administration of SW033291 while PGE2 levels increased, Paragraphs [0333-0334], and that subjects with Alzheimer's disease had elevated levels of 15-PGDH, Paragraph [03335]. Applicant argues that Markowitz et al. provides no teaching and/or evidence that shows that a 15-PGDH inhibitor could be used to treat or prevent BBB permeability in a subject and that when administered could protect and/or decrease BBB permeability in a subject as claimed.
Applicant further argues that claims 23 and 24 are patentable over Markowitz et al. in view of Wong et al. for at least the same reasons as detailed above for claim 20 since claims 23 and 24 depend from claim 20.
These arguments are found not persuasive for the same reasons as detailed above for the double patenting rejection.
Specifically, the claims as amended claim a method preventing or treating blood brain barrier (BBB) permeability in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a 15- PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, wherein the subject has or is at risk of a neurodegenerative condition, disorder, or disease where BBB permeability occurs and the BBB permeability includes impaired BBB integrity and increased BBB vascular permeability. The claims further recite that the subject is a subject having been identified as having Alzheimer’s disease. Thus the claims of the instant application are drawn to the treatment of a patient with Alzheimer’s disease comprising the administration of a 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject.
Claims 12, 17 and 19 of Markowitz et al. specifically claim a method of treating Alzheimer’s disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor, wherein the 15-PGDH inhibitor is formula (V); and wherein the 15-PGDH inhibitor is formula (IX).
The cited claims of the instant application are anticipated since Markowitz et al. specifically teaches and claims administering to a subject having Alzheimer’s disease, a therapeutically effective amount of a 15-PGDH inhibitor, wherein the 15-PGDH inhibitor is SW033291 having the following structure:
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, and therefore the method of Markowitz et al. will inherently prevent or treat blood brain barrier permeability in said subject as claimed in the instant claims. Moreover, the method of Markowitz et al. will inherently protect the BBB and/or decrease BBB permeability in the subject as claimed.
It is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
In the instant case, the use of the claimed compound in treating Alzheimer’s disease is known in the art and thus the effect or result of said method in preventing or treating blood brain barrier permeability is also inherently present in the prior art. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999).
Thus the cited claims of the instant application are still anticipated by the teachings of Markowitz despite the amendments to the claims and thus remain rejected under 35 USC 102. In addition, claims 23 and 24 are also rejected under 35 USC 103 for the same reasons. Accordingly, for these reasons the previous rejections under 35 USC 102 and 103 are hereby maintained and modified rejections necessitated by Applicant’s amendments to the claims are detailed below.
This action is FINAL.
Drawings
The drawings are objected to because Figures 1-9 are too small and illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 20, 22, 25-27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-28 of copending Application No. 19/327,153 (U.S. Publication No. 2026/0007642). Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of copending ‘153 are drawn to the treatment of a patient with Alzheimer’s disease comprising the administration of a compound of formula (V) such as SW033291 having the following structure:
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Although copending ‘153 does not claim treating or preventing blood brain barrier permeability in the subject as claimed, the method of copending ‘153 will inherently treat or prevent blood brain barrier permeability and protect the BBB and/or decrease BBB permeability in said subject as claimed in the instant claims.
It is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
In the instant case, the use of the claimed compound in treating Alzheimer’s disease which is an age-related dementia is claimed in copending ‘153 and thus the effect or result of said method in treating or preventing blood brain barrier permeability and protecting the BBB and/or decreasing BBB permeability is also inherently present in the claims of copending ‘153. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999).
Thus the cited claims of the instant application would be anticipated over the cited claims of copending ‘153.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 23 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 23-28 of copending Application No. 19/327,153 (U.S. Publication No. 2026/0007642) as applied to claims 20, 22, 25-27 and 29 above, and further in view of Wong et al. (Neurochemistry International, 1992, Volume 21, Issue 2, pages 197-202).
Claim 23 of the instant application claims the subject has a decrease or increase in the level of at least one of PGE2, 16-keto-PGE2, PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE brain tissue compared to a control.
Claim 24 of the instant application claims the subject has a decrease in the level of at least one, at least two, or at least three or more of PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE in brain tissue of the subject.
The claims of copending ‘153 do not specifically claim that the subject with Alzheimer’s disease has a decrease or increase of the proteins in brain tissue as claimed.
Wong et al. demonstrates that as compared to control patients, patients with Alzheimer’s disease have a significant reduction in prostanoid levels in the post-mortem frontal cortex as compared to control (page 199 and abstract). Wong et al. teaches that as compared to control, post-mortem brains of patients with AD had a 46% downregulation in AA metabolism measured by total prostanoid production (page 199). Overall, the production of PGE2 (45% reduction), PGF2α (48% reduction) and PGD2 (63% reduction) were significantly lower in the frontal cortex of patients with AD compared to control (page 199).
Accordingly, claims 23 and 24 of the instant application are rendered obvious since patients with Alzheimer’s disease as claimed in copending ‘153 are known in the art as taught by Wong et al. to have decreased levels of PGE2, PGF2α, and PGD2 in brain tissue. Thus treating a subject having a decrease in the level of at least one of PGE2, 16-keto-PGE2, PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE in brain tissue of the subject with Alzheimer’s disease as claimed is rendered obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 20, 22, 25-27 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Markowitz et al. WO 2018/017582 A1 (Provided on IDS dated 10/18/2023).
Claims 20, 22, 25-27 and 29 of the instant application claim a method preventing or treating blood brain barrier (BBB) permeability in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor to protect the BBB and/or decrease BBB permeability in the subject, wherein the subject has age-related dementia, and the 15-PGDH inhibitor is SW033291 having the following structure:
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Markowitz et al. teaches compositions and methods that promote the generation or the survival of neurons in the mammalian brain as well as to compositions and methods of treating diseases, disorders, and/or conditions of the nervous system [0005]. Markowitz et al. teaches that it was found that compounds that inhibit, reduce, and/or antagonize short-chain dehydrogenase activity, such as 15-PGDH inhibitors, can be used to increase PGE2 levels in the nervous system (e.g., brain) of a mammal, wherein PGE2 elevates cyclic AMP via binding to EP2 and EP4 receptors, which are highly expressed in the cerebral cortex, hippocampus, and striatum [0005]. Markowitz et al. teaches that stimulation of these receptors with PGE2 by administration of a compound that inhibits, reduces, and/or antagonizes 15-PGDH acivity, such as with a 15-PGDH inhibitor described therein, can promote neuroprotection in a subject from axonal degeneration, neuronal cell death, and/or glia cell damage after injury, augment neuronal signaling underlying learning and memory, stimulate neuronal regeneration after injury, and/or treat diseases, disorders, and/or conditions of the nervous system [0005].
Markowitz et al. teaches the disease, disorder, and/or condition of the nervous system, which can be treated with the 15-PGDH inhibitors, can include at least one of a neurological disorder, a neuropsychiatric disorder, a neural injury, a neural toxicity disorder, a neuropathic pain, or a neural degenerative disorder, such as at least one of Alzheimer's disease, dementias related to Alzheimer's disease, Parkinson's, Lewy diffuse body diseases, senile dementia, Huntington's disease, Gilles de Ia Tourette's syndrome, multiple sclerosis, amyotrophic lateral sclerosis, hereditary motor and sensory neuropathy, diabetic neuropathy, progressive supranuclear palsy, epilepsy, or Jakob- Creutzfieldt disease [0006]-[0007].
Markowitz et al. teaches that the 15-PGDH inhibitors can be administered to a subject or neurons of the subject to promote the survival, growth, development and/or function of the neurons, particularly, the central nervous system (CNS), brain, cerebral, and hippocampal neurons, and in particular, the 15-PGDH inhibitors can be used stimulate hippocampal neurogenesis, for the treatment of neuropsychiatric and neurodegenerative diseases, including Alzheimer's disease [0009].
Markowitz et al. teaches that the 15-PGDH inhibitors can be administered to a subject at an amount effective to increase prostaglandin levels in the nervous system (e.g., brain), wherein the 15-PGDH inhibitor can include a compound having formula (V) having the same structure as the compounds as claimed in claim 29 of the instant application ([0010]-[0011] and [00128]). Markowitz et al. teaches that the 15-PGDH inhibitors can inhibit the enzymatic activity of recombinant 15-PGDH at an IC50 of less than 1 mM [00137]. Markowitz et al. teaches that the 15-PGDH inhibitor can increase the cellular levels of PGE2 [00138].
Markowitz et al. specifically teaches that the 15-PGDH inhibitor is a compound of formula (IX) having the following structure:
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[00144]. Markowitz et al. specifically teaches that the 15-PDGH inhibitor having formula (IX) was found to: i) inhibit recombinant 15-PGDH at 1 nM concentration; ii) inhibit 15-PGDH in cell lines at 100 nM concentration, iii) increase PGE2 production by cell lines; iv) is chemically stable in aqueous solutions over broad pH range; v) is chemically stable when incubated with hepatocyte extracts, vi) is chemically stable when incubated with hepatocyte cell lines; vii) shows 253 minutes plasma half-life when injected IP into mice; and viii) shows no immediate toxicity over 24 hours when injected IP into mice at 0.6 mmole/per mouse and at 1.2 mmole/per mouse and also no toxicity when injected IP into mice at 0.3 mmole/per mouse twice daily for 21 days [00145].
Markowitz et al. specifically demonstrates the effects of formula (IX) also called SW033291 in the brain and on learning and memory (Example 2 pages 143-145). Markowitz et al. specifically demonstrates that SW033291 administration increases the level of PGE2 in the brain and improves learning and memory [00327]-[00330].
Markowitz et al. specifically demonstrates 15-PGDH mRNA expression in the neurons of the mouse hippocampus, a region of the brain involved in learning and memory, and that is an early site of damage in Alzheimer’s disease and that the 15-PGDH enzyme activity can be readily inhibited in the brain following IP injection of the 15-PGDH inhibitor [00331]-[00333].
Markowitz et al. demonstrates that PGE2 levels are elevated in rat brain cortex 30, 120, and 180 minutes following a single IP injection of (+)-SW033291 at the noted doses [00334].
Markowitz et al. further demonstrates increases in the levels of 15-PGDH in brain tissue of subjects with Alzheimer’s disease relative to age matched control subjects without Alzheimer’s disease and markedly elevated levels of 15-PGDH enzyme in brain tissue (occipital and frontal cortex) of patients with Alzheimer’s disease (average age 85), relative to age matched (average age 85) control subjects without Alzheimer’s disease [00335].
Claims 12, 17 and 19 of Markowitz et al. specifically claim a method of treating Alzheimer’s disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor, wherein the 15-PGDH inhibitor is formula (V); and wherein the 15-PGDH inhibitor is formula (IX).
The cited claims of the instant application are anticipated since Markowitz et al. specifically teaches and claims administering to a subject having an age-related dementia which is Alzheimer’s disease, a therapeutically effective amount of a 15-PGDH inhibitor, wherein the 15-PGDH inhibitor is SW033291 having the following structure:
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, and therefore the method of Markowitz et al. will inherently treat or prevent blood brain barrier permeability and protect the BBB and/or decrease BBB permeability in said subject as claimed in the instant claims.
It is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
In the instant case, the use of the claimed compound in treating Alzheimer’s disease which is an age-related dementia is known in the art and thus the effect or result of said method in treating or preventing blood brain barrier permeability and protecting the BBB and/or decreasing BBB permeability in the subject is also inherently present in the prior art. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999).
Thus the cited claims of the instant application are rejected.
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 23 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Markowitz et al. WO 2018/017582 A1 as applied to claims 20, 22, 25-27 and 29 above, and further in view of Wong et al. (Neurochemistry International, 1992, Volume 21, Issue 2, pages 197-202).
Claim 23 of the instant application claims the subject has a decrease or increase in the level of at least one of PGE2, 16-keto-PGE2, PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE brain tissue compared to a control.
Claim 24 of the instant application claims the subject has a decrease in the level of at least one, at least two, or at least three or more of PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE in brain tissue of the subject.
Markowitz et al. is as set forth above.
Markowitz et al. does not specifically teach that the subject with age-related dementia such as Alzheimer’s disease has a decrease or increase of the proteins in brain tissue as claimed.
However, Markowitz et al. demonstrates that increases in the levels of 15-PGDH in brain tissue of subjects with Alzheimer’s disease relative to age matched control subjects without Alzheimer’s disease and markedly elevated levels of 15-PGDH enzyme in brain tissue (occipital and frontal cortex) of patients with Alzheimer’s disease (average age 85), relative to age matched (average age 85) control subjects without Alzheimer’s disease [00335]. Furthermore, Markowitz et al. demonstrates that PGE2 levels are elevated in rat brain cortex 30, 120, and 180 minutes following a single IP injection of (+)-SW033291 at the noted doses [00334]. Thus Markowitz et al. demonstrates that 15-PGDH inhibition leads to elevated PGE2 levels in the brain.
Accordingly, it would have been obvious to a person of ordinary skill in the art that subjects with Alzheimer’s disease having markedly elevated levels of 15-PGDH enzyme in brain tissue as demonstrated by Markowitz et al. would also have markedly reduced levels of PGE2 levels in the brain since the 15-PGDH enzyme leads to PGE2 degradation. Thus a subject having a decrease of the level of PGE2 as claimed in claim 23 of the instant application is rendered obvious.
In addition, Wong et al. demonstrates that as compared to control patients, patients with Alzheimer’s disease have a significant reduction in prostanoid levels in the post-mortem frontal cortex as compared to control (page 199 and abstract). Wong et al. teaches that as compared to control, post-mortem brains of patients with AD had a 46% downregulation in AA metabolism measured by total prostanoid production (page 199). Overall, the production of PGE2 (45% reduction), PGF2α (48% reduction) and PGD2 (63% reduction) were significantly lower in the frontal cortex of patients with AD compared to control (page 199).
Accordingly, claim 24 is rendered obvious since patients with Alzheimer’s disease as taught in Markowitz et al. are known in the art as taught by Wong et al. to have decreased levels of PGE2, PGF2α, and PGD2 in brain tissue as compared to control. Thus treating a subject having a decrease in the level of at least one of PGF2a, 6-keto-PGF1a, TXB2, PGD2, PGJ2, TN-E, 15-HETE, 12-HETE, 8-HETE, or 5-HETE in brain tissue of the subject with Alzheimer’s disease as claimed is rendered obvious.
Thus claims 23 and 24 of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-10 and 21 are canceled. Claims 11-19, 28 and 30 are withdrawn. Claims 20, 22-27 and 29 are rejected. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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