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
The present application claims priority to the applications, 63/174,750 and PCT/US2022/024927, with effective filing dates of 14 April 2021 and 14 April 2022, respectively.
Claim Status
This Office Action is in response to Applicant’s Amendment filed, 13 October 2023, wherein Applicant amended claims 3-5, 11, 14-16, 22, and 25-26 and canceled claims 17-19.
Claims 1-16 and 20-26 are pending.
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.
1. Claims 1, 4 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
1. Claims 1, 6, 9, 12, 20, and 23 specify the generic term “a protein tyrosine phosphatase 4A3 (PTP4A3) inhibitor,” and claims 4, 8, 11, 14, 21, and 25 specify a PTP4A3 inhibitor with structure
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, wherein R4 is selected from the group consisting of -H, -OH, -OC1-4 alkyl, -ORa, trifluoroC1-4 alkoxy, -SC1-4 alkyl, -SRa, -SO2-C1-4 alkyl, -SO2Ra, -SOC1-4 alkyl, -SORa,-SO2NHRb, -NRcRd,halo,-C1-12 alkyl, -C2-6 alkenyl, -C2-6 alkynyl, -C3-6cycloalkyl, phenyl, benzyl, monocyclic heteroaryl optionally substituted with Rb, -C3-6 cycloalkyl, -C4-7 heterocycloalkyl containing one or two of O, S, and N, -OC(O)Rb, -OC(O)Rb, -P(O)(ORb)1-2, -P(S)(ORb)1-2, - P(O)(NRcRd)1 -P(S)(NRcRd)1-2, -O(CH2-CH2-O)1-4CH3, -CN, -NO2, - C(O)C1-4 alkyl, and -C(O)-Rb,Ra is selected from the group consisting of -C3-6 cycloalkyl, -C2-s alkenyl, -C2-6alkynyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with Rb;Rb in each instance is independently selected from the group consisting of H, halo, -OH, -GOGH, -C1-12 alkyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with -C2-s alkenyl, -C2-s alkynyl, trifluroC1-4 alkoxy, -OC1-4 alkyl, - O(CH2-CH2-O)1-4CH3, -O-phenyl, -O- benzyl, -NC1-4 alkyl, -N-phenyl, and - N-benzyl, or -N-monocyclic heteroaryl; Rcand Rd are each independently selected from the group consisting of H, -C1-4alkyl, -C(O)-C1-4 alkyl, -C(O)-Re, -C1-4 alkyl-Re, -SO2-Ra, -SO2-C1-4 alkyl,phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with Rb, or or Rc and Rd taken together with the nitrogen to which they are attached represent an optionally substituted monocyclic heterocycloalkyl containing one or more of O, S, and N.
However, the specification details a method of treating only via administering KVX-053, which is also known as 7-imino-2-phenylthieno[3,2- c]pyridine-4,6(5H,7H)-dione, JMS-631-053, and JMS-053 (CAS No. 1954650-11-3) as defined in the specification (page 44, lines 11-15). The specification describes the ability of KVX-053 to block spike protein-induced endothelial barrier disruption in human lung endothelial cells (page 59, lines 28-32; page 60, lines 1-7), spike protein-induced proinflammatory chemokine release in vivo (page 60, lines 9-16), chemical-induced lung injury in vivo (page 60, lines 19-31; page 61, lines 1-3), and SARS-CoV-2 Spike 1 protein-mediated pulmonary alveolar epithelial barrier function and cytokine release in vivo (page 65, lines 12-34; page 66, lines 1-12). Further, the specification describes the use of analog, KVX-038, as a negative control, because the specification discloses that KVX-038 is an inactive analog (page 66, line 10).
Rivas (“A Screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3),” BioRxiv, 2020, 1-30) teaches that there is no singular well-established class of PTP4A3 (also known as PRL-3) inhibitors nor a singular PTP4A3 binding site (abstract, page 3, paragraph 2; page 4, paragraph 3). Rivas further teaches that there is a high degree of sequence homology between the PRL family members and that the PRL-3 active site is shallower, wider, and more hydrophobic, making design of PRL-specific inhibitors challenging (page 4, paragraphs 2 and 3). Rivas specifies pharmacokinetic and off-target concerns with several inhibitors, in particular JMS-053, which have prevented further development (page 4, paragraph 3).
Rivas further specifies that JMS-053 is proposed to allosterically inhibit PTP4A3 at the WDP loop, but Rivas also suggests other PRL inhibitors, such as candesartan, bind to a secondary pocket at the opposite side of the active site adjacent to the CX5R motif (page 11, paragraph 2). Rivas discloses that both the WDP loop and CX5R motif harbor the catalytic residues of classical dual-specificity phosphatases and suggests that drug binding is sensitive to PRL-3 conformation due to allosteric site location (page 11, paragraph 3). However, Rivas specifies that there is no available structure of PRL-3 in complex with any inhibitor and that this lack of information makes it challenging to define residues in PRL-3 and functional groups in the compounds that are key to PRL-3-inhibitor interaction (page 11, paragraph 2). Further, McQueeney (Oncotarget, 2018, 9(9), 8223-8240) specifies that JMS-038 (corresponding to the inactive analog, KVX-038) is a close structural analog to JMS-053 and is inactive, which further underscores the unpredictability of the art (page 8224, column 2, paragraph 3).
Thus, the specification does not describe the claimed subject matter that would reasonably
convey to one of skill in the art a method of treating a viral infection via any PTP4A3 inhibitor, much less a PTP4A3 inhibitor with structure
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, wherein R4 is selected from the group consisting of -OH, -OC1-4 alkyl, -ORa, trifluoroC1-4 alkoxy, -SC1-4 alkyl, -SRa, -SO2-C1-4 alkyl, -SO2Ra, -SOC1-4 alkyl, -SORa,-SO2NHRb, -NRcRd,halo,-C1-12 alkyl, -C2-6 alkenyl, -C2-6 alkynyl, -C3-6cycloalkyl, phenyl, benzyl, monocyclic heteroaryl optionally substituted with Rb, -C3-6 cycloalkyl, -C4-7 heterocycloalkyl containing one or two of O, S, and N, -OC(O)Rb, -OC(O)Rb, -P(O)(ORb)1-2, -P(S)(ORb)1-2, - P(O)(NRcRd)1 -P(S)(NRcRd)1-2, -O(CH2-CH2-O)1-4CH3, -CN, -NO2, - C(O)C1-4 alkyl, and -C(O)-Rb,Ra is selected from the group consisting of -C3-6 cycloalkyl, -C2-s alkenyl, -C2-6alkynyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl,benzyl, or monocyclic heteroaryl is optionally substituted with Rb;Rb in each instance is independently selected from the group consisting of H,halo, -OH, -GOGH, -C1-12 alkyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with -C2-s alkenyl, -C2-s alkynyl, trifluroC1-4 alkoxy, -OC1-4 alkyl, - O(CH2-CH2-O)1-4CH3, -O-phenyl, -O- benzyl, -NC1-4 alkyl, -N-phenyl, and - N-benzyl, or -N-monocyclic heteroaryl; Rc and Rd are each independently selected from the group consisting of H, -C1-4alkyl, -C(O)-C1-4 alkyl, -C(O)-Re, -C1-4 alkyl-Re, -SO2-Ra, -SO2-C1-4 alkyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with Rb, or Rc and Rd taken together with the nitrogen to which they are attached represent an optionally substituted monocyclic heterocycloalkyl containing one or more of O, S, and N.
2. Claims 1, 9, 12, and 20 specify the generic term “a viral infection,” and claims 5 and 15 specify an influenza A infection.
However, the specification only details a method of treating a pulmonary disease arising from SARS-CoV-2 infection (page 65, lines 12-14; page 66, lines 15-16). Further, the specification describes the ability of KVX-053 to block spike protein-induced endothelial barrier disruption in human lung endothelial cells (page 59, lines 28-32; page 60, lines 1-7), spike protein-induced proinflammatory chemokine release in vivo (page 60, lines 9-16), chemical-induced lung injury in vivo (page 60, lines 19-31; page 61, lines 1-3), and SARS-CoV-2 Spike 1 protein-mediated pulmonary alveolar epithelial barrier function and cytokine release in vivo (page 65, lines 12-34; page 66, lines 1-12).
Regarding any virus, Drysdale (J Infection, 2017, 74, 541-546) teaches that rhinoviruses are small viruses with broad genetic diversity and are the most common cause of respiratory tract infection (page 541, column 1, paragraph 1; page 541, column 2, paragraph 3). Further, Drysdale specifies that the treatment and vaccine for rhinovirus continues to remain elusive due to incomplete understanding of the immune response to rhinovirus (page 544, column 1, paragraph 3).
Regarding influenza, Dou (Front. Immunol., 2018, 9(1581), 1-17) teaches that there are four types of larger influenza viruses, sub-sectioned into type A, B, C, and D (page 1, paragraph 1). Dou specifies that a significant challenge in battling influenza A is the constant evolution of the surface antigens (hemagglutinin and neuraminidase), which further underscores the unpredictability of the art (page 2, column 2, paragraph 2).
Thus, the specification does not describe the claimed subject matter that would reasonably
convey to one of skill in the art a method of treating any viral infection, and in particular, influenza A.
3. Claims 1, 9, 12, 20, and 23 specify the generic term “a subject.”
However, the specification only details a method of treating SARS-CoV-2 in vitro and in murine models (page 65, lines 12-15; page 66, lines 15-22). The specification defines a “subject” as “a member of species for which treatment and/or prevention of a disease or disorder using the compositions and methods of the presently disclosed subject matter might be desirable. Accordingly, the term ‘subject’ is intended to encompass in some embodiments any member of the Kingdom Animalia including, but not limited to the phylum Chordata (e.g., members of Classes Osteichthyes10 (bony fh), Amphibia (amphibians), Reptilia (reptiles), Aves (birds), and Mammalia (mammals), and all Orders and Families encompassed therein” (page 39, lines 5-11).
Leenaars (J Transl Med, 2019, 17(223), 1-22) teaches that current drug development is handicapped by high attrition rates and that many molecules that were promising during preclinical development fail during subsequent clinical testing (page 1, column 1, paragraph 1). Leenaars further teaches that animals and humans are complex systems and therefore always unpredictable (page 2, column 1, paragraph 1), which further underscores the unpredictability of the art and translation of promising candidate in murine model to other species.
However, Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) teaches small molecules for SARS-CoV-2 treatment (abstract). Panoutsopoulos further discloses the mechanism of infection utilized by SARS-CoV-2 in humans (page 529, column 1, paragraphs 3-5; column 2, paragraphs 1-5). Further, Panoutsopoulos discusses the most promising compound and how they are able to intervene in the mechanism of infection of SARS-CoV-2 (page 529, column 2, paragraph 6; page 530, column 1, paragraph 1).
Thus, while the specification does describe the claimed subject matter in vitro, in mice, and in human, it does not describe the claimed subject matter that would reasonably convey to one of skill in the art a method of treating any subject, particularly, Kingdom Animalia including, but not limited to the phylum Chordata (e.g., members of Classes Osteichthyes10 (bony fh), Amphibia (amphibians), Reptilia (reptiles), Aves (birds), and Mammalia (mammals) (excluding mice and humans), and all Orders and Families encompassed therein.
4. Claim 1, 2, 4-6, 8, 9, 11, 12, 14, 15, 20, 21, 23, and 25 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of (1) treating or preventing a SARS-CoV-2 via administration of KVX-053 in vitro, in mouse, and in humans, (2) reducing inflammation and/or damage resulting from a SARS-CoV-2 via administration of KVX-053 in vitro, in mouse, and in humans, and (3) treating chemical damage via administration of KVX-053 in vitro, in mouse, and in humans, does not reasonably provide enablement for treating any viral infection in any subject via any PTP4A3 inhibitor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP § 2164.01(a), considers the following factors:
Breadth of the Claims
The instant claims are directed to a method of treating or preventing a viral infection in a subject via administration of a PTP4A3 inhibitor. Thus, encompassing all viral infections and prevention thereof, all of Kingdom Animalia (as defined in the specification, page 39, lines 5-11), and all PTP4A3 inhibitors.
As such, the breadth of the claims is great.
Level of Skill in the Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Art
Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) teaches small molecules for SARS-CoV-2 treatment (abstract). Panoutsopoulos further discloses the mechanism of infection utilized by SARS-CoV-2 in humans (page 529, column 1, paragraphs 3-5; column 2, paragraphs 1-5). Specifically, Panoutsopoulos teaches the mechanism of infection of SARS-CoV-2 in that the virus gains access to host cell cytosol by proteolytic cleavage of S protein, which is followed by fusion of viral and cellular membranes and release of the viral genome into the cytoplasm (page 529, column 2, paragraph 1). Further, Panoutsopoulos discusses the most promising compounds and how they are able to intervene in the mechanism of infection of SARS-CoV-2 (page 529, column 2, paragraph 6; page 530, column 1, paragraph 1).
McQueeney further specifies that PTP4A3 has a central role in metastases formation and angiogenesis and leads to an altered microenvironment and creates a dysfunctional endothelium, which loses critical barrier properties (page 8224, column 1, paragraph 1) as evidenced by Peng (Molecule Cancer, 2009, 8(110), 1-13). Peng teaches that PRL-3 (another name for PTP4A3) plays a causative role in promoting cell motility, invasion, and metastasis (page 2, column 1, paragraph 1; page 2, column 1, paragraph 2). McQueeney specifies that JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Additionally, Beeraka (Front Immunol, 2020, 11(552925), 1-22) teaches possible prevention of SARS-CoV-2 infection via modulation of Spike protein via inhibition of the angiotensin converting enzyme-2 (page 10, column 1, paragraph 1).
However, Drysdale (J Infection, 2017, 74, 541-546) teaches that rhinoviruses are small viruses with broad genetic diversity and are the most common cause of respiratory tract infection (page 541, column 1, paragraph 1; page 541, column 2, paragraph 3). Further, Drysdale specifies that the treatment and vaccine for rhinovirus continues to remain elusive due to incomplete understanding of the immune response to rhinovirus (page 544, column 1, paragraph 3).
Regarding influenza, Dou (Front. Immunol., 2018, 9(1581), 1-17) teaches that there are four types of larger influenza viruses, sub-sectioned into type A, B, C, and D (page 1, paragraph 1). Dou specifies that a significant challenge in battling influenza A is the constant evolution of the surface antigens (hemagglutinin and neuraminidase (page 2, column 2, paragraph 2).
Leenaars (J Transl Med, 2019, 17(223), 1-22) teaches that current drug development is handicapped by high attrition rates and that many molecules that were promising during preclinical development fail during subsequent clinical testing (page 1, column 1, paragraph 1). Leenaars further teaches that animals and humans are complex systems and therefore always unpredictable (page 2, column 1, paragraph 1).
Rivas (“A Screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3),” BioRxiv, 2020, 1-30) teaches that there is no singular well-established class of PTP4A3 (also known as PRL-3) inhibitors nor a singular PTP4A3 binding site (abstract, page 3, paragraph 2; page 4, paragraph 3). Rivas further teaches that there is a high degree of sequence homology between the PRL family members and that the PRL-3 active site is shallower, wider, and more hydrophobic, making design of PRL-specific inhibitors challenging (page 4, paragraphs 2 and 3). Rivas specifies pharmacokinetic and off-target concerns with several inhibitors, in particular JMS-053, which have prevented further development (page 4, paragraph 3).
Rivas further specifies that JMS-053 is proposed to allosterically inhibit PTP4A3 at the WDP loop, but Rivas also suggests other PRL inhibitors, such as candesartan, bind to a secondary pocket at the opposite side of the active site adjacent to the CX5R motif (page 11, paragraph 2). Rivas discloses that both the WDP loop and CX5R motif harbor the catalytic residues of classical dual-specificity phosphatases and suggests that drug binding is sensitive to PRL-3 conformation due to allosteric site location (page 11, paragraph 3). However, Rivas specifies that there is no available structure of PRL-3 in complex with any inhibitor and that this lack of information makes it challenging to define residues in PRL-3 and functional groups in the compounds that are key to PRL-3-inhibitor interaction (page 11, paragraph 2). Further, McQueeney (Oncotarget, 2018, 9(9), 8223-8240) specifies that JMS-038 (corresponding to the inactive analog, KVX-038) is a close structural analog to JMS-053 and is inactive (page 8224, column 2, paragraph 3).
Thus, while the prior art teaches methods of (1) treating or preventing a SARS-CoV-2 via administration of KVX-053 in vitro, in mouse, and in humans, (2) reducing inflammation and/or damage resulting from a SARS-CoV-2 via administration of KVX-053 in vitro, in mouse, and in humans, and (3) treating chemical damage via administration of KVX-053 in vitro, in mouse, and in humans, these methods are taught for the treatment of specific viral infections, specific subject, and specific PTP4A3 inhibitor.
Predictability in the Art
Regarding viral infections, Drysdale specifies that the treatment and vaccine for rhinovirus continues to remain elusive due to incomplete understanding of the immune response to rhinovirus (page 544, column 1, paragraph 3). Dou specifies that a significant challenge in battling influenza A is the constant evolution of the surface antigens (hemagglutinin and neuraminidase (page 2, column 2, paragraph 2), underscoring the unpredictability in the art of developing a small molecule inhibitor for treating influenza.
Regarding translation of method of treating to different biological species, Leenaars teaches that animals and humans are complex systems and therefore always unpredictable (page 2, column 1, paragraph 1), which further underscores the unpredictability of the art and translation of promising candidate in murine models to other species.
Regarding predictability in active PTP4A3 inhibitor, Rivas specifies that there is no available structure of PRL-3 in complex with any inhibitor and that this lack of information makes it challenging to define residues in PRL-3 and functional groups in the compounds that are key to PRL-3-inhibitor interaction (page 11, paragraph 2). Further, McQueeney specifies that JMS-038 (corresponding to the inactive analog, KVX-038) is a close structural analog to JMS-053 and is inactive, which further underscores the unpredictability of the art (page 8224, column 2, paragraph 3). Additionally, Rivas teaches that there is no singular well-established class of PTP4A3 (also known as PRL-3) inhibitors nor a singular PTP4A3 binding site (abstract, page 3, paragraph 2; page 4, paragraph 3).
Working Examples
While the instant specification teaches a method of (1) treating SARS-CoV-2 via KVX-053 in vitro, in mouse, and in human, (2) reducing inflammation from cytokines/chemokines originating from SARS-CoV-2 via KVX-053 in vitro, in mouse, and in human, and (3) treating chemical damage via KVX-053 in vitro, in mouse, and in human, the instant specification does not teach any PTP4A3 inhibitor, much less a PTP4A3 inhibitor with structure
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, wherein R4 is selected from the group consisting of -OH, -OC1-4 alkyl, -ORa, trifluoroC1-4 alkoxy, -SC1-4 alkyl, -SRa, -SO2-C1-4 alkyl, -SO2Ra, -SOC1-4 alkyl, -SORa,-SO2NHRb, -NRcRd,halo,-C1-12 alkyl, -C2-6 alkenyl, -C2-6 alkynyl, -C3-6cycloalkyl, phenyl, benzyl, monocyclic heteroaryl optionally substituted with Rb, -C3-6 cycloalkyl, -C4-7 heterocycloalkyl containing one or two of O, S, and N, -OC(O)Rb, -OC(O)Rb, -P(O)(ORb)1-2, -P(S)(ORb)1-2, - P(O)(NRcRd)1 -P(S)(NRcRd)1-2, -O(CH2-CH2-O)1-4CH3, -CN, -NO2, - C(O)C1-4 alkyl, and -C(O)-Rb,Ra is selected from the group consisting of -C3-6 cycloalkyl, -C2-s alkenyl, -C2-6alkynyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with Rb; Rb in each instance is independently selected from the group consisting of H,halo, -OH, -GOGH, -C1-12 alkyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with -C2-s alkenyl, -C2-s alkynyl, trifluroC1-4 alkoxy, -OC1-4 alkyl, - O(CH2-CH2-O)1-4CH3, -O-phenyl, -O- benzyl, -NC1-4 alkyl, -N-phenyl, and - N-benzyl, or -N-monocyclic heteroaryl; Rc and Rd are each independently selected from the group consisting of H, -C1-4alkyl, -C(O)-C1-4 alkyl, -C(O)-Re, -C1-4 alkyl-Re, -SO2-Ra, -SO2-C1-4 alkyl, phenyl, benzyl, and monocyclic heteroaryl, wherein the phenyl, benzyl, or monocyclic heteroaryl is optionally substituted with Rb, or Rc and Rd taken together with the nitrogen to which they are attached represent an optionally substituted monocyclic heterocycloalkyl containing one or more of O, S, and N can treat or prevent any viral infection (in particular, influenza) in any subject.
Thus, it is not possible to determine all the types of PTP4A3 inhibitor that can treat SARS-CoV-2, all the types of viral infection that KVX-053 can treat, and all the types of subject that can be treated.
Quantity of Experimentation
The amount of experimentation required to determine which PTP4A3 inhibitor, which viral infection, in which subject, in what amounts, what order, would be astronomical. A skilled artisan would be required to start with proof-of-concept and proceed through all levels of lead identification and optimization, which is invention and not development; this is an unduly burdensome amount of experimentation.
As such, while the specification is enabling for a method of (1) treating or preventing SARS-CoV-2 via KVX-053 in vitro, in mouse, and in human, (2) reducing inflammation from cytokines/chemokines originating from SARS-CoV-2 via KVX-053 in vitro, in mouse, and in human, and (3) treating chemical damage via KVX-053 in vitro, in mouse, and in human, it does not reasonably provide enablement for a method of treating all viral infections via any PTP4A3 inhibitor in any subject. Further, the specification does not reasonably provide enablement for treating influenza.
Claim Rejections - 35 USC § 102
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claim 1 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated Lazo (WO 2020/102243, filed 12 Nov 2019).
Lazo teaches PTP4A3 inhibitors with activity against cervical cancer, in which human papillomavirus (HPV) plays a causal role, as evidenced by Wu (page 674, column 1, paragraph 2; Brit J Cancer, 2003, 89, 672-675).
Regarding claim 1, Lazo teaches PTP4A3 inhibitors, which treat cervical cancer ([0064]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
6. Claims 1-16 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) in view of McQueeney (Oncotarget, 2018, 9(9), 8223-8240).
Panoutsopoulos teaches a method of treating SARS-CoV-2 via small molecules in humans (abstract).
Panoutsopoulos further teaches the mechanism of infection of SARS-CoV-2 in that the virus gains access to host cell cytosol by proteolytic cleavage of S protein, which is followed by fusion of viral and cellular membranes and release of the viral genome into the cytoplasm (page 529, column 2, paragraph 1).
Regarding claim 1, Panoutsopoulos fails to teach a PTP4A3 inhibitor.
McQueeney teaches the PTP4A3 inhibitor:
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(page 8226, Figure 2A). Further, McQueeney specifies that PTP4A3 has a central role in metastases formation and angiogenesis and leads to an altered microenvironment and creates a dysfunctional endothelium, which loses critical barrier properties (page 8224, column 1, paragraph 1) as evidenced by Peng (Molecule Cancer, 2009, 8(110), 1-13). Peng teaches that PRL-3 (another name for PTP4A3) plays a causative role in promoting cell motility, invasion, and metastasis (page 2, column 1, paragraph 1; page 2, column 1, paragraph 2). McQueeney further specifies that JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the PTP4A3 inhibitor of McQueeney to develop a method of treating SARS-CoV-2 in humans via KVX-053, which is JMS-053 as defined in the specification (page 44, lines 11-15) to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Panoutsopoulos teaches small molecules and drugs that are already in use and FDA approved for other diseases, and show promise for treatment of COVID-19,
-Panoutsopoulos teaches the S-protein—receptor interaction is the primary determinant for a coronavirus to infect a host cell and governs tissue specificity of the virus,
-Panoutsopoulos teaches fusion occurs within acidified endosomes and allows for mixing of viral and cellular membranes, resulting in release of viral genome into the cytoplasm,
-McQueeney teaches JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer and that JMS-053 is a potent PTP4A3 inhibitor,
-McQueeney teaches that PTP4A3 has a central role in metastases formation and angiogenesis, ultimately leading to an altered microenvironment,
-McQueeney teaches that PTP4A3 phosphatases interact with a variety of protein partners, including cell surface receptors, and
-McQueeney teaches that JMS-053 exposure restored compromised barrier function and that JMS-053 and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins.
As such, an artisan having ordinary skill in the art would have been motivated to make
such a selection, to predictably arrive at a method of treating or preventing SARS-CoV-2 infection via administration of the PTP4A3 inhibitor, JMS-053.
Regarding claim 2, Panoutsopoulos teaches the disease or disorder is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 3, Panoutsopoulos teaches the disease or disorder associated with a viral infection is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 4, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 5, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 6, Panoutsopoulos teaches a method of reducing or inhibiting virus-induced alveolar inflammation and/or damage via administering a small molecule (abstract; page 529, column 1, paragraph 3; page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 7, Panoutsopoulos teaches the disease or disorder is induced by infection with SARS-CoV-2 (page 529, column 1, paragraph 3; page 532, column 1, paragraph 2).
Regarding claim 8, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 9, Panoutsopoulos teaches a method of reducing or inhibiting induction of an inflammatory cytokine via a small molecule and that cytokines are known to be elevated among SARS-CoV-2 patients, creating a cytokine storm which leads to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 10, Panoutsopoulos teaches the inflammatory cytokine is IL-1, IL-6, or TNF (page 532, column 1, paragraph 2).
Regarding claim 11, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 12, Panoutsopoulos teaches a method of reducing or inhibiting a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 13, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 14, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 15, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 16, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
Regarding claim 23, Panoutsopoulos teaches a method of treating or preventing chemical damage to a lung from the cytokine storm associated with SARS-CoV-2 (page 532, column 1, paragraph 2) as evidenced by Cleveland Clinic (“Cytokines,” Cleveland Clinic, 3 Jan 2023, < my.clevelandclinic.org/health/body/24585-cytokines>, accessed 16 Jan 2026). Cleveland Clinic teaches that cytokines are chemical messengers in the immune system that control inflammation and signal immune cells to fight harmful substances (page 1, paragraphs 1 and 2). Thus, Panoutsopoulos teaches treating damage caused by SARS-CoV-2, which lead to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 24, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 25, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 26, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
7. Claims 16 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) in view of McQueeney (Oncotarget, 2018, 9(9), 8223-8240) as applied to claim 1-16 above, and further in view of Lazo ‘663 (U.S. Patent No. 10,308,663, issued 4 Jun 2019).
Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) in view of McQueeney (Oncotarget, 2018, 9(9), 8223-8240) are applied as discussed in the above 35 U.S.C. 103 rejection above).
Regarding claim 16, while the combination of Panoutsopoulos and McQueeney teaches a method of treating a SARS-CoV-2 infection via intraperitoneal administration of the PTP4A3 inhibitor, JMS-053, they differ from that of the instantly claimed invention in that they do not explicitly teach a method of treating a SARS-CoV-2 infection via oral, intravenous, intramuscular, subcutaneous, intranasal, or pulmonary administration of the PTP4A3 inhibitor, JMS-053.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the
effective filing date of the instantly claimed invention, to exemplify the methods of Panoutsopoulos and McQueeney with the administration method of Lazo ‘663 to arrive at the instantly claimed invention.
One of ordinary skill in the art would have been motivated to combine the method of treating of Panoutsopoulos and McQueeney with the administration method of Lazo ‘663 with a reasonable expectation of success, because Lazo ‘663 teaches PTP4A3 inhibitor compounds, compositions, uses, methods of use, and methods of preparation (abstract). Further, Lazo ‘663 teaches JMS-053 is a potent inhibitor of PTP4A3 in vitro and specifies methods of preparation of JMS-053 (column 3, lines 11-14; Table 2, column 20, lines 16-39; Figure 1). Further, Lazo ‘663 teaches JMS-053 may be administered orally, by intravenous, intramuscular, topical, or subcutaneous routes (column 13, lines 26-31). Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable.
Regarding claim 20, Lazo ‘663 teaches a composition of JMS-053 and route of administration (column 13, lines 26-31). Panoutsopoulos teaches a method of treating or preventing a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule in an effective amount (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function in an effective amount of compound (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 21, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 22, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 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.
8. Claim 1-16 and 20-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 7, and 9-11 of U.S. Patent No. 10,308,663 in view of Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) and McQueeney (Oncotarget, 2018, 9(9), 8223-8240).
U.S. Patent No. 10,308,663 claims a composition of
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, wherein R4 can be H, and a method of inhibiting protein-tyrosine phosphatase in a cell, comprising contacting the cell with a compound of Formula III, and when R4 is H, the compound is JMS-053 (claims 3, 7, and 9-11 of ‘663).
Regarding claim 1, ‘663 fails to teach a method of treating or preventing a viral infection as well as the role of JMS-053 on endothelial cell permeability.
Panoutsopoulos teaches a method of treating SARS-CoV-2 via small molecules in humans (abstract). Panoutsopoulos further teaches the mechanism of infection of SARS-CoV-2 in that the virus gains access to host cell cytosol by proteolytic cleavage of S protein, which is followed by fusion of viral and cellular membranes and release of the viral genome into the cytoplasm (page 529, column 2, paragraph 1).
McQueeney teaches the PTP4A3 inhibitor:
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(page 8226, Figure 2A). Further, McQueeney specifies that PTP4A3 has a central role in metastases formation and angiogenesis and leads to an altered microenvironment and creates a dysfunctional endothelium, which loses critical barrier properties (page 8224, column 1, paragraph 1) as evidenced by Peng (Molecule Cancer, 2009, 8(110), 1-13). Peng teaches that PRL-3 (another name for PTP4A3) plays a causative role in promoting cell motility, invasion, and metastasis (page 2, column 1, paragraph 1; page 2, column 1, paragraph 2). McQueeney further specifies that JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the PTP4A3 inhibitor of ‘663 to develop a method of treating SARS-CoV-2 in humans via KVX-053, which is JMS-053 as defined in the specification (page 44, lines 11-15) to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-‘663 teaches a method of inhibiting protein-tyrosine phosphatase in a cell,
-‘663 teaches the PTP4A3 inhibitor, JMS-053,
-Panoutsopoulos teaches small molecules and drugs that are already in use and FDA approved for other diseases, and show promise for treatment of COVID-19,
-Panoutsopoulos teaches the S-protein—receptor interaction is the primary determinant for a coronavirus to infect a host cell and governs tissue specificity of the virus,
-Panoutsopoulos teaches fusion occurs within acidified endosomes and allows for mixing of viral and cellular membranes, resulting in release of viral genome into the cytoplasm,
-McQueeney teaches JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer and that JMS-053 is a potent PTP4A3 inhibitor,
-McQueeney teaches that PTP4A3 has a central role in metastases formation and angiogenesis, ultimately leading to an altered microenvironment,
-McQueeney teaches that PTP4A3 phosphatases interact with a variety of protein partners, including cell surface receptors, and
-McQueeney teaches that JMS-053 exposure restored compromised barrier function and that JMS-053 and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins.
As such, an artisan having ordinary skill in the art would have been motivated to make
such a selection, to predictably arrive at a method of treating or preventing SARS-CoV-2 infection via administration of the PTP4A3 inhibitor, JMS-053.
Regarding claim 2, Panoutsopoulos teaches the disease or disorder is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 3, Panoutsopoulos teaches the disease or disorder is associated with a viral infection is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 4, ‘663 teaches JMS-053, wherein R4 is H (claim 9 of ‘663).
Regarding claim 5, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 6, Panoutsopoulos teaches a method of reducing or inhibiting virus-induced alveolar inflammation and/or damage via administering a small molecule (abstract; page 529, column 1, paragraph 3; page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 7, Panoutsopoulos teaches the disease or disorder is induced by infection with SARS-CoV-2 (page 529, column 1, paragraph 3; page 532, column 1, paragraph 2).
Regarding claim 8, ‘663 teaches JMS-053, wherein R4 is H (claim 9 of ‘663).
Regarding claim 9, Panoutsopoulos teaches a method of reducing or inhibiting induction of an inflammatory cytokine via a small molecule and that cytokines are known to be elevated among SARS-CoV-2 patients, creating a cytokine storm which leads to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 10, Panoutsopoulos teaches the inflammatory cytokine is IL-1, IL-6, or TNF (page 532, column 1, paragraph 2).
Regarding claim 11, ‘663 teaches JMS-053, wherein R4 is H (claim 9 of ‘663).
Regarding claim 12, Panoutsopoulos teaches a method of reducing or inhibiting a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 13, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 14, ‘663 teaches JMS-053, wherein R4 is H (claim 9 of ‘663).
Regarding claim 15, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 16, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
Regarding claim 20, ‘663 teaches a composition of JMS-053 and route of administration (claim 3 of ‘663). Panoutsopoulos teaches a method of treating or preventing a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule in an effective amount (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function in an effective amount of compound (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 21, ‘663 teaches JMS-053, wherein R4 is H (claim 9 of ‘663).
Regarding claim 22, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 23, Panoutsopoulos teaches a method of treating or preventing chemical damage to a lung from the cytokine storm associated with SARS-CoV-2 (page 532, column 1, paragraph 2) as evidenced by Cleveland Clinic (“Cytokines,” Cleveland Clinic, 3 Jan 2023, < my.clevelandclinic.org/health/body/24585-cytokines>, accessed 16 Jan 2026). Cleveland Clinic teaches that cytokines are chemical messengers in the immune system that control inflammation and signal immune cells to fight harmful substances (page 1, paragraphs 1 and 2). Thus, Panoutsopoulos teaches treating damage caused by SARS-CoV-2, which lead to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 24, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 25, ‘663 teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 26, ‘663 may be administered orally, by intravenous, intramuscular, topical, or subcutaneous routes (column 13, lines 26-31). Additionally, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
9. Claims 1-16 and 23-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3 and 6-7 of U.S. Patent Publication No. 2022/0017534 in view of Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) and McQueeney (Oncotarget, 2018, 9(9), 8223-8240).
U.S. Patent Publication No. 2022/0017534 claims a method of treating a subject suffering from cancer with a PTP4A3 inhibitor and that cancer is cervical cancer (claims 2-3). ‘534 claims a method of inhibiting a protein-tyrosine phosphatase in a cell, and the protein tyrosine phosphatase is PTP4A3 (claims 6-7).
Regarding claim 1, ‘534 teaches a method of treating a disease (cervical cancer) associated with a viral infection (HPV, as evidenced by Wu (page 674, column 1, paragraph 2; Brit J Cancer, 2003, 89, 672-675)) via administration of a PTP4A3 inhibitor (claims 2-3).
Regarding claim 2, ‘534 fails to teach a method of treating or preventing a viral infection or the role of JMS-053 on endothelial cell permeability.
Panoutsopoulos teaches a method of treating SARS-CoV-2 via small molecules in humans (abstract). Panoutsopoulos further teaches the mechanism of infection of SARS-CoV-2 in that the virus gains access to host cell cytosol by proteolytic cleavage of S protein, which is followed by fusion of viral and cellular membranes and release of the viral genome into the cytoplasm (page 529, column 2, paragraph 1).
McQueeney teaches the PTP4A3 inhibitor:
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(page 8226, Figure 2A). Further, McQueeney specifies that PTP4A3 has a central role in metastases formation and angiogenesis and leads to an altered microenvironment and creates a dysfunctional endothelium, which loses critical barrier properties (page 8224, column 1, paragraph 1) as evidenced by Peng (Molecule Cancer, 2009, 8(110), 1-13). Peng teaches that PRL-3 (another name for PTP4A3) plays a causative role in promoting cell motility, invasion, and metastasis (page 2, column 1, paragraph 1; page 2, column 1, paragraph 2). McQueeney further specifies that JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select a PTP4A3 inhibitor of ‘534 to develop a method of treating SARS-CoV-2 in humans to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-‘534 teaches a method of inhibiting protein-tyrosine phosphatase in a cell,
-‘534 teaches PTP4A3 inhibitors,
-Panoutsopoulos teaches small molecules and drugs that are already in use and FDA approved for other diseases and show promise for treatment of COVID-19,
-Panoutsopoulos teaches the disease or disorder is acute respiratory distress syndrome,
-Panoutsopoulos teaches the S-protein—receptor interaction is the primary determinant for a coronavirus to infect a host cell and governs tissue specificity of the virus,
-Panoutsopoulos teaches fusion occurs within acidified endosomes and allows for mixing of viral and cellular membranes, resulting in release of viral genome into the cytoplasm,
-McQueeney teaches JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer and that JMS-053 is a potent PTP4A3 inhibitor,
-McQueeney teaches that PTP4A3 has a central role in metastases formation and angiogenesis, ultimately leading to an altered microenvironment,
-McQueeney teaches that PTP4A3 phosphatases interact with a variety of protein partners, including cell surface receptors, and
-McQueeney teaches that JMS-053 exposure restored compromised barrier function and that JMS-053 and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins.
As such, an artisan having ordinary skill in the art would have been motivated to make
such a selection, to predictably arrive at a method of treating or preventing SARS-CoV-2 infection via administration of the PTP4A3 inhibitor, wherein the disease is acute respiratory distress syndrome.
Regarding claim 3, Panoutsopoulos teaches the disease or disorder is associated with a viral infection is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 4, McQueeney teaches JMS-053, which is KVX-053 as defined in the specification (page 44, lines 11-15), wherein R4 is H (page 8226, Figure 2A).
Regarding claim 5, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 6, Panoutsopoulos teaches a method of reducing or inhibiting virus-induced alveolar inflammation and/or damage via administering a small molecule (abstract; page 529, column 1, paragraph 3; page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 7, Panoutsopoulos teaches the disease or disorder is induced by infection with SARS-CoV-2 (page 529, column 1, paragraph 3; page 532, column 1, paragraph 2).
Regarding claim 8, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 9, Panoutsopoulos teaches a method of reducing or inhibiting induction of an inflammatory cytokine via a small molecule and that cytokines are known to be elevated among SARS-CoV-2 patients, creating a cytokine storm which leads to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 10, Panoutsopoulos teaches the inflammatory cytokine is IL-1, IL-6, or TNF (page 532, column 1, paragraph 2).
Regarding claim 11, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 12, Panoutsopoulos teaches a method of reducing or inhibiting a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 13, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 14, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 15, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 16, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
Regarding claim 23, Panoutsopoulos teaches a method of treating or preventing chemical damage to a lung from the cytokine storm associated with SARS-CoV-2 (page 532, column 1, paragraph 2) as evidenced by Cleveland Clinic (“Cytokines,” Cleveland Clinic, 3 Jan 2023, < my.clevelandclinic.org/health/body/24585-cytokines>, accessed 16 Jan 2026). Cleveland Clinic teaches that cytokines are chemical messengers in the immune system that control inflammation and signal immune cells to fight harmful substances (page 1, paragraphs 1 and 2). Thus, Panoutsopoulos teaches treating damage caused by SARS-CoV-2, which lead to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 24, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 25, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 26, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
10. Claims 1-16 and 23-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 and 11-12 of U.S. Patent Publication No. 2021/0395266 in view of Panoutsopoulos (Genes & Diseases, 2020, 7, 528-534) and McQueeney (Oncotarget, 2018, 9(9), 8223-8240).
U.S. Patent Publication No. 2021/0395266 claims a method of treating a subject suffering from cancer with a PTP4A3 inhibitor and that cancer is cervical cancer (claims 7-8). ‘266 claims a method of inhibiting a protein-tyrosine phosphatase in a cell, and the protein tyrosine phosphatase is PTP4A3 (claims 11-12).
Regarding claim 1, ‘266 teaches a method of treating a disease (cervical cancer) associated with a viral infection (HPV, as evidenced by Wu (page 674, column 1, paragraph 2; Brit J Cancer, 2003, 89, 672-675)) via administration of a PTP4A3 inhibitor (claims 7-8).
Regarding claim 2, ‘266 fails to teach a method of treating or preventing a viral infection or the role of JMS-053 on endothelial cell permeability.
Panoutsopoulos teaches a method of treating SARS-CoV-2 via small molecules in humans (abstract). Panoutsopoulos further teaches the mechanism of infection of SARS-CoV-2 in that the virus gains access to host cell cytosol by proteolytic cleavage of S protein, which is followed by fusion of viral and cellular membranes and release of the viral genome into the cytoplasm (page 529, column 2, paragraph 1).
McQueeney teaches the PTP4A3 inhibitor:
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(page 8226, Figure 2A). Further, McQueeney specifies that PTP4A3 has a central role in metastases formation and angiogenesis and leads to an altered microenvironment and creates a dysfunctional endothelium, which loses critical barrier properties (page 8224, column 1, paragraph 1) as evidenced by Peng (Molecule Cancer, 2009, 8(110), 1-13). Peng teaches that PRL-3 (another name for PTP4A3) plays a causative role in promoting cell motility, invasion, and metastasis (page 2, column 1, paragraph 1; page 2, column 1, paragraph 2). McQueeney further specifies that JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select a PTP4A3 inhibitor of ‘266 to develop a method of treating SARS-CoV-2 in humans to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-‘266 teaches a method of inhibiting protein-tyrosine phosphatase in a cell,
-‘266 teaches PTP4A3 inhibitors,
-Panoutsopoulos teaches small molecules and drugs that are already in use and FDA approved for other diseases and show promise for treatment of COVID-19,
-Panoutsopoulos teaches the disease or disorder is acute respiratory distress syndrome,
-Panoutsopoulos teaches the S-protein—receptor interaction is the primary determinant for a coronavirus to infect a host cell and governs tissue specificity of the virus,
-Panoutsopoulos teaches fusion occurs within acidified endosomes and allows for mixing of viral and cellular membranes, resulting in release of viral genome into the cytoplasm,
-McQueeney teaches JMS-053 displayed anticancer activity in a murine xenograft model of drug resistant human ovarian cancer and that JMS-053 is a potent PTP4A3 inhibitor,
-McQueeney teaches that PTP4A3 has a central role in metastases formation and angiogenesis, ultimately leading to an altered microenvironment,
-McQueeney teaches that PTP4A3 phosphatases interact with a variety of protein partners, including cell surface receptors, and
-McQueeney teaches that JMS-053 exposure restored compromised barrier function and that JMS-053 and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins.
As such, an artisan having ordinary skill in the art would have been motivated to make
such a selection, to predictably arrive at a method of treating or preventing SARS-CoV-2 infection via administration of the PTP4A3 inhibitor, wherein the disease is acute respiratory distress syndrome.
Regarding claim 3, Panoutsopoulos teaches the disease or disorder is associated with a viral infection is acute respiratory distress syndrome (page 532, column 1, paragraph 2).
Regarding claim 4, McQueeney teaches JMS-053, which is KVX-053 as defined in the specification (page 44, lines 11-15), wherein R4 is H (page 8226, Figure 2A).
Regarding claim 5, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 6, Panoutsopoulos teaches a method of reducing or inhibiting virus-induced alveolar inflammation and/or damage via administering a small molecule (abstract; page 529, column 1, paragraph 3; page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 7, Panoutsopoulos teaches the disease or disorder is induced by infection with SARS-CoV-2 (page 529, column 1, paragraph 3; page 532, column 1, paragraph 2).
Regarding claim 8, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 9, Panoutsopoulos teaches a method of reducing or inhibiting induction of an inflammatory cytokine via a small molecule and that cytokines are known to be elevated among SARS-CoV-2 patients, creating a cytokine storm which leads to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 10, Panoutsopoulos teaches the inflammatory cytokine is IL-1, IL-6, or TNF (page 532, column 1, paragraph 2).
Regarding claim 11, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 12, Panoutsopoulos teaches a method of reducing or inhibiting a pulmonary disease (acute respiratory distress syndrome) associated with SARS-CoV-2 via a small molecule (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 13, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 14, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 15, Panoutsopoulos teaches the viral infection is SARS-CoV-2 (abstract).
Regarding claim 16, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
Regarding claim 23, Panoutsopoulos teaches a method of treating or preventing chemical damage to a lung from the cytokine storm associated with SARS-CoV-2 (page 532, column 1, paragraph 2) as evidenced by Cleveland Clinic (“Cytokines,” Cleveland Clinic, 3 Jan 2023, < my.clevelandclinic.org/health/body/24585-cytokines>, accessed 16 Jan 2026). Cleveland Clinic teaches that cytokines are chemical messengers in the immune system that control inflammation and signal immune cells to fight harmful substances (page 1, paragraphs 1 and 2). Thus, Panoutsopoulos teaches treating damage caused by SARS-CoV-2, which lead to acute respiratory distress syndrome (page 532, column 1, paragraph 2). McQueeney teaches the PTP4A3 inhibitor, JMS-053, and its role in restoring compromised barrier function (page 8226, Figure 2A; page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 24, Panoutsopoulos teaches a viral infection causing a mixing of viral and cellular membranes, which is endothelial barrier disruption (page 529, column 2, paragraph 1). McQueeney teaches JMS-053 restored compromised barrier function and can target endothelial cell hyperpermeability, which enables infiltration of cells and soluble proteins (page 8233, column 1, paragraph 2; page 8233, column 2, paragraph 2).
Regarding claim 25, McQueeney teaches JMS-053, wherein R4 is H (page 8226, Figure 2A).
Regarding claim 26, McQueeney teaches female mice are inject intraperitoneally with JMS-053 (page 8237, column 2, paragraph 1).
Conclusion
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622