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 .
Status of the claims
Claims 1-14 and 36-38 are pending and are examined.
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 06/18/2024, 07/23/2024, 01/10/2025 and 02/21/2025 were considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Specifically, in line 2, variants denoted United Kingdom, South African and Brazilian do not have a structural correspondent so that the metes and bounds of the claim could not be determined.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
It is not clear what is the comparison term for the conservative substitution in the heavy chain or light chain sequence since no reference antibody is mentioned. As such the metes and bounds of the claim could not be determined.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14 and 36-38 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358).
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
The claims are drawn to a method of preventing or treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by administration of a therapeutically effective amount of a CHl3L1 inhibitor, wherein the inhibitor of CHl3L1 may be, inter alia, an antibody, antibody reagent, antigen-binding fragment thereof, or chimeric antigen receptor (CAR), that specifically binds a CHl3L1 polypeptide.
Based on the effect of the regulation of three SARS-CoV-2 related gene expression (ACE2, TMPRSS2 and CTSL), the specification discloses inhibition of the these genes by Kasugamycin, Flavopiridol and anti-CHI3L1 antibodies (denoted generic FRG) that have the complementarity determining regions (CDRs) of: (a) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4; (b) a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5; (c) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6; (d) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1; (e) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and (f) a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3.
However, the claims broadly encompass a genus of methods of treatment that use any CHI3L1 inhibitor (including Chimeric Antigen Receptors). The present claims attempt to claim methods that employ any type of inhibitors of CHI3L1, wherein the specification provides evidence of possession of methods of inhibiting three SARS-CoV-2 related gene expression by Kasugamycin, Flavopiridol and anti-CHI3L1 antibodies only.
Thus, the instant disclosure, including the claims fail to disclose a representative number of species falling with the scope of the genus or structural common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus. One of skill in the art would conclude that Applicant was not in possession of the invention claimed in its full scope but just for methods of treatment using Kasugamycin, Flavopiridol and anti-CHI3L1.
Claims 1-14 and 36-38 are 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 treatment of a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), does not reasonably provide enablement for prevention of this disease. 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 independent claim 1 is drawn to a method of preventing or treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising administering a therapeutically effective amount of a CHl3L1 inhibitor to a subject at risk of, or afflicted with, a Covid-19 infection. However, the phrase "preventing a disorder", given its broadest reasonable interpretation in light of the teachings in the specification, requires that absolutely no cell, nor tissue, or individual would present any symptom of a disorder after treatment with CHI3L1 inhibitors. There is no evidence, either in the specification or in the prior art, that any method to date can accomplish this goal. The only method to increase the chances of the apparition of the COVID-19 is by vaccination. The specification presents the results of experiments demonstrating that Kasugamycin, Flavopiridol and anti-CHI3L1 antibodies (denoted generic FRG) inhibit the expression of three SARS-CoV-2 related gene (ACE2, TMPRSS2 and CTSL). However, there is no support for the prevention of any disorder or disease, as is required by the claims, and neither can such support be obtained through reasonable extrapolation of the data or teachings in the art, with the exception, as mentioned, of vaccines against SARS-CoV-2.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
Claims 1, 2, 4-5, 9-14 and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Elias et al. (WO2018129261 -cited by Applicant) in view of Abrams et al. (Asthma and Covid-19. Can Med. Assoc. J. , 192, E551, early release 04/24/2025) and Xia et al. (Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343-355, 2020 -cited by Applicant).
The claims are drawn to a method of preventing or treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by administration of a therapeutically effective amount of a CHl3L1 inhibitor, wherein the inhibitor of CHl3L1 may be, inter alia, an antibody, antibody reagent, antigen-binding fragment thereof, or chimeric antigen receptor (CAR), that specifically binds a CHl3L1 polypeptide. The antibody comprise the complementarity determining regions (CDRs) of: (a) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4; (b) a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5; (c) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6; (d) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1; (e) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and (f) a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3. The antibody may also comprise a heavy chain sequence having the amino acid sequence of SEQ ID NO: 13 and a light chain sequence having the amino acid sequence of SEQ ID NO: 14. The method is performed when a subject is diagnosed as having COVID-19 or was exposed to another subject infected with SARS-CoV-2. Further, the subject has the typical symptoms associated with the Covid-19.
Elias et al. teaches a method of treating, inter alia, asthma, comprising administering a therapeutically-effective amount of a CH13L1 inhibitor to a subject (abstract). The reference disclose that the chitinase-like protein called chitinase 3-like-1 (Chi3L1; also called Chil1 in mice and YKL-40 in man) has been implicated in asthma. It has been demonstrated that the levels of circulating Chi3L1 are increased in human asthma where they correlate with disease severity ([0005]). The reference claims (claim 32) a method of treating asthma in a patient by administering an anti-CHI3L1 antibody (FRG) having the variable heavy chain of SEQ ID NO: 36 and the variable light chain of SEQ ID NO: 38 and comprising the 6CDRs set of the instant SEQ ID NOs: 1-6 . The sequence are identical with SEQ ID NO: 13 and 14 (respectively).
Asthma can be triggered by such things as exposure to an allergen (allergic asthma), or non-allergens (non-allergic asthma) such as cold air, pollution (e.g., ozone), warm air, moist air, exercise or exertion, or emotional stress. The most common triggers are viral illnesses such as those that cause the common cold ([0129]).
Since Covid-19 was not known at the publication date of the WO reference, the reference is silent about treating Covid-19.
Abrams et al. teaches that asthma is a known risk factor for COVID-19 since SARS-CoV-2 triggers asthma exacerbation. The reference also presents a list of symptoms associated with Covid-19.
Xia et al. teaches a potential treatment for wild-type SARS-CoV-2. The reference discloses EK1C4 as the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection. The peptide is highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2.
Since Elias et al. teaches asthma could be triggered by respiratory infections, and bolstered by the teachings of Abrams et al, it would have been obvious to a person of ordinary skill in the art at the time that the invention was filed to have considered use of a CHl3L1 inhibitor of Elias et al. for treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of Xia et al. to relieve acute respiratory symptoms that could lead to asthma with a reasonable expectation of success. This is because the Elias reference indicate that availability and the successful use of the CHl3L1 inhibitor antibodies for treating a condition that is exacerbated by Covid-19. A skilled artisan would have been compelled to consider the tools existent in the art to address the health care emergency imposed by Covid-19 and at least try to alleviate the symptoms with what was known in the art.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Elias et al. (WO2018129261 -cited by Applicant) in view of Abrams et al. (Asthma and Covid-19. Can Med. Assoc. J. , 192, E551, early release 04/24/2020) and Xia et al. (Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 30, 343-355, 2020 -cited by Applicant) and in further view of Becerra-Flores et al. (SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate. Int. J. Clin. Practice, 74, e13525, 2020 -cited by Applicant).
The claim adds the limitation that the variant SARS-CoV-2 is selected from the group consisting of: D614G, E484K, United Kingdom, South African, and Brazilian.
The teachings of Elias et al., Abrams et al. and Xia et al. were presented supra and they were silent about the variant claimed instantly.
Becerra-Flores et al. teaches SARS-CoV-2 viral spike G614 mutation renders it more pathogenic. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection (abstract).
It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have considered use of a CHl3L1 inhibitor of Elias et al. for treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of Xia et al. made more pathogenic as taught by Becerra-Flores et al., to relieve acute respiratory symptoms that could lead to asthma with a reasonable expectation of success. This is because the Elias reference indicate that availability and the successful use of the CHl3L1 inhibitor antibodies for treating a condition that is exacerbated by Covid-19. A skilled artisan would have been compelled to consider the tools existent in the art to address the health care emergency imposed by Covid-19 and at least try to alleviate the symptoms with what was known in the art.
Claims 1, 2, 4-8, 12-14 and 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Chupp et al. (WO2019060675) in view Elias et al. , Abrams et al. Xia et al. (all cited by supra).
The claims are drawn to a method of preventing or treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by administration of a therapeutically effective amount of a CHl3L1 inhibitor, wherein the inhibitor of CHl3L1 may be, inter alia, an antibody, antibody reagent, antigen-binding fragment thereof, or chimeric antigen receptor (CAR), that specifically binds a CHl3L1 polypeptide. The antibody comprise the complementarity determining regions (CDRs) of: (a) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 4; (b) a light chain CDR2 having the amino acid sequence of SEQ ID NO: 5; (c) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 6; (d) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 1; (e) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 2; and (f) a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 3. The antibody may also comprise a heavy chain sequence having the amino acid sequences of SEQ ID NOs: 15-26 and a light chain sequence having the amino acid sequences of SEQ ID NOs: 27-34. The method is performed when a subject is diagnosed as having COVID-19 or was exposed to another subject infected with SARS-CoV-2. Further, the subject has the typical symptoms associated with the Covid-19.
Chupp et al. disclosed that chitinase 3-like1/Brp-39/YKL-40 (i.e., YKL-40) has an important role in inflammation and inflammatory diseases and disorders such as asthma (p.40). This inflammation is relieved by administering selective inhibitors of CHI3L1/YKL-40 and methods of treatment of asthma based on this disclosure are claimed (claims 8-12). The inhibitors are anti-YKL-40 antibodies which comprise the full CDR set claimed in the instant Application. The antibodies of the reference have the variable heavy chain structures of SEQ ID NOs: 1-12, which are identical with the SEQ ID NOs: 15-26 of the instant Application. The antibodies of the reference have the variable light chain structures of SEQ ID NOs: 13-20, which are identical with the SEQ ID NOs: 27-34 of the instant Application.
The teaching of Chupp et al. is silent about treating Covid-19 because the condition was not known at the publication date of the WO reference.
The teachings of Elias et al. Abrams et al. and Xia et al., presented supra, establish the connection between asthma, Covid-19 and CHI3L1?YKL-40 inhibition.
Since Elias et al. teaches asthma could be triggered by respiratory infections, and bolstered by the teachings of Abrams et al, it would have been obvious to a person of ordinary skill in the art at the time that the invention was filed to have considered use of a CHl3L1/YKL-40 antibodies of Chupp et al. for treating a Covid-19 infection induced by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of Xia et al. to relieve acute respiratory symptoms that could lead to asthma with a reasonable expectation of success. This is because the Elias reference and Chupp et al. reference indicate that availability and the successful use of the CHl3L1/YKL-40 antibodies for treating a condition that is exacerbated by Covid-19. A skilled artisan would have been compelled to consider the tools existent in the art to address the health care emergency imposed by Covid-19 and at least try to alleviate the symptoms with what was known in the art.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647