DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of invention Group II (claims 2, 15, 16, and 19-23, drawn to a method of treating or preventing ocular surface disease in a mammalian subject in need thereof, the method comprising administering to the subject an inflammasome inhibitor in an amount effective to treat or prevent the ocular surface disease or damage) and species election without traverse of species B (wherein the ocular surface disease is dry eye syndrome, meibomian gland dysfunction, blepharitis, ocular rosacea allergic conjunctivitis, chemical and thermal ocular burns, pterygium, pinguecula, conjunctivochalasis or limbal stem cell deficiency) in the reply filed on 2/26/2026 is acknowledged. Claims 2, 15 and 20-23 read on the elected species, with at least claims 2 and 20-23 being generic.
3. Claims 1, 3-7, 10-11, 14, and 16, 17-18, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/3/2026. The amendments filed 2/26/2026 are acknowledged. Claims 1, 3-7, 10-11, 14, 16, 17-18, and 24 are withdrawn. Claims 2, 15, and 19-23 are pending and under examination.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted both on 03/20/2024 and the references cited therein have been considered, unless indicated otherwise.
Specification
5. The use of the terms Gibco, Invitrogen, SimpleStep ELISA, KEYENCE, Promega, which is a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
6. Claim 15 objected to because of the following informalities: The word pterygium and pinguecula in claim 15 do not require capitalization. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
The following rejection is a written description rejection. This written description rejection has two issues. One issue regarding written description is lack of structure and the other issue is regarding claiming “caspase-2” without support in the specification.
7. First, claims 2, 15, 16, and 19-23 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.
The MPEP states that the purpose of the written description requirement is to ensure
that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are drawn to Claim 2 is drawn to a method of treating or preventing ocular surface disease in a mammalian subject in need thereof, the method comprising administering to the subject an inflammasome inhibitor in an amount effective to treat or prevent the ocular surface disease or damage
The specification teaches that inflammasome inhibitor is an agent which inhibits expression of one or more components of the inflammasome (paragraph 33). The specification further teaches that the inflammasome inhibitor can be a polynucleotide which includes, but not limited to, antisense oligonucleotides (ASO), short hairpin RNA (shRNA), small interfering RNA (siRNA), or micro RNA (miRNA), CRISPR Cas9 protein, and it can also be an antibody or an antigen- binding fragment thereof. In some embodiments, the inflammasome inhibitor is an siRNA, shRNA, ASO, or miRNA that inhibits the expression of caspase-1, ASC, NLRP1, NLRP2, NLRP3, or AIM2 (paragraph 36).
The issue with regard to the written description provision is that the genus of different form of inflammasome inhibitor is not adequately described. The claims and specification provides no guidance regarding which amino acids can be modified in the inflammasome inhibitor, while maintaining any given function. Therefore, these structures (i.e., different forms) are claimed only be their functional characteristics and the specification fails to provide sufficient correlation between the claimed functional characteristics and the necessary structural components (i.e., critical domains within the sequences).
Furthermore, Applicants have not shown possession of a representative number of species that have the claimed function(s). While the specification clearly sets forth a correlation between the genus of inflammasome inhibitor, and the claimed functions, this correlation does not appear to be clearly present in the breadth of the claims. As noted above, the claims broadly encompass the genus inflammasome inhibitor. Thus, the genus has substantial variation because of the numerous alternatives and combinations permitted. There is no description of the structure common to the members of the genus such that one of skill in the art can visualize or recognize the members of the genus. Therefore, only one species has been described and this is not considered to be representative of the breadth of the genus. Therefore, given the lack of structure function correlation and the lack of a representative number of species, the specification provides insufficient written description to support the genus encompassed by the claim.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed combination therapies, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481,1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565,1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Punta et al. (PLoS Comput Biol 4(10): e1000160, 2008) teach that homology (both orthology and paralogy) does not guarantee conservation of function (See page 2). Punta et al. teach that relatively small difference in sequence can sometimes cause quite radical changes in functional properties, such as a change of enzymatic action, or even loss or acquisition of enzymatic activity itself (See page 2). Punta et al. teach that it is also apparent that there is no sequence similarity threshold that guarantees that two proteins share the same function (see page 2). Punta et al. teach that homology between two proteins does not guarantee that they have the same function, not even when sequence similarity is very high (including 100% sequence identity) (See page 2 and table 2). Punta et al. teach that proteins live and function in 3D, and therefore structural information is very helpful for predicating function (See page 4). However, as with sequence, two proteins having the same overall architecture, and even conserved functional residues, can have unrelated functions (See page 4). Punta et al. teach that still; structural knowledge is an extremely powerful tool for computational function prediction (See page 5).
Similarly, Whisstock et al. (Quarterly Reviews in Biophysics. 36(3):307-340, 2007) teach that the prediction of protein function from sequence and structure is a difficult problem (See abstract). Although many families of proteins contain homologues with the same function, homologous proteins often have different functions as the sequences progressively diverge (See page 309). Whisstock et al. teach that moreover, even closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function (See page 309). Further, Whisstock et al. note that in some instances, even sequences that are the same can have different functions. For example, eye lens proteins in the suck are identical in sequence to active lactate dehydrogenase and enolase in other tissues, although they do not encounter the substrates in the eye (See page 310). Whisstock et al. teach that assigning a function to an amino acid sequence based upon similarity becomes significantly more complex as the similarity between the sequence and a putative homologue fall (See page 321). Whisstock et al. teach that while it is hopeful that similar proteins will share similar functions, substitution of a single, critically placed amino acid in an active-site may be sufficient to alter a protein’s role fundamentally (See pages 321-323).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Song et al. (Molecular Biology of the Cell, 15:1287–1296, March 2004) who teach that substitution of alanine for aspartate in survivin results in the conversion of survivins’ apoptotic function from anti-apoptotic to proapoptotic and changes in its subcellular localization (See page 1287-1289). Moreover, Defeo-Jones et al. (Molecular and Cellular Biology, Sept. 1989, p. 4083-4086) teach that the conservative substitution of lysine for arginine at position 42 completely eliminated biological activity (See abstract and pages 4084-4085). These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Additionally, Bork (Genome Research, 2000; 10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
Given not only the teachings of Punta et al., Whisstock et al., Song et al., Burgess et al., and Defeo-Jones et al., but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the claimed proteins having the required function(s) could not be predicted based on sequence identity. Clearly, it could not be predicted that polypeptide or a variant that shares only partial homology with a disclosed protein will function in a given manner. Therefore, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the proteins per se and thereby does not provide adequate written description support for which structural features of any given polypeptide would predictably retain their functional activities.
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). 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 Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). 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).
Adequate written description requires more than a mere statement that is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chungai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
The University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an Applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2dat1966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Second, claim 21 is 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.
When establishing a 35 U.S.C. 112(a) written description rejection, the burden is on the Examiner to set forth a prima facie case providing reasons why the specification is deficient and thus the claims that relies thereon are rejected. It is important to note that each claim is given its broadest reasonable interpretation in light of and consistent with the written description (see MPEP 2111 and 2163(II)). Additionally, a full review of the application must be done to understand how the applicant provides support for the claimed invention during each element and/or step, which includes the specification, drawings, structural chemical formulas, etc. (see MPEP 2163(II)). Finally, a determination as to whether the applicant was in possession of the claimed invention at the time of filing is made by considering (see MPEP 2163(II)):
The variety of ways that that applicant may show possession,
The level of skill and knowledge in the art, and
The predictability in the art.
The claim is drawn, either inherently or explicitly, to the possession of a capase-2 or would require a caspase-2 in order to perform the method as described. The specification does not provide a method of making a caspase-2, nor a way to source a caspase-2 from a third-party. Additionally, the supplemental information (e.g., the drawings), capase-1 concentration information, wherein the samples were collected from subjects. There was no indication that caspase-2 was obtained from the subjects at any point during this study.
Although the claims are inclusive of multiple variant of caspase, including as caspase-1 and caspase-5 (caspase-11 in rodents), the processing of the pro-inflammatory cytokines IL-13 and IL-18, and the cell death process of pyroptosis (paragraph 31), the specification does not make mention or disclose the caspase 2. There was no mention of caspase-2, thus, a fully functional and publicly available caspase-2 would not be predictable in the art, and it cannot be assumed that it would be well-known or conventional in the art, therefore requiring a disclosure in detail.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565,1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
The state of the art regarding Caspase-2 is taught by Brown-Suedel, et al (Brown-Suedel AN and Bouchier-Hayes L (2020) Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond. Front. Cell Dev. Biol. 8:610022. doi: 10.3389/fcell.2020.610022). Brown-Seudel, et al. teach caspase-2 is classified as an initiator caspase, which respond to apoptotic stimuli by initiating the apoptotic cascade. It is further taught that Caspase-2 is considered a pro-apoptotic caspase that has a unique role as a tumor suppressor in multiple tissue types. Emerging evidence demonstrates that caspase-2 not only has an apoptotic role, but that it can also contribute to the regulation of other cellular events including cell division. However, there are only a few fully verified caspase-2 substrates that are known and, therefore, how caspase-2 can regulate both apoptosis and non-apoptotic processes to suppress tumors has been difficult to unravel
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). 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 Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). 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 University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an Applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2dat1966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
In view of the fact that the examples provided do not demonstrate possession of a caspase-2, the application has not identified a caspase-2 and one of ordinary skill in the art at the time of filing would not have recognized the possession of a caspase-2, there is insufficient written description support for a caspase-2.
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 102
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
8. Claims 2 and 15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being unpatentable over O’Neill, et al. (US Patent No: US 11,130,731 B2, issued 09/28/2021, filed 08/07/219).
Instant claim 2 teaches a method of treating or preventing ocular surface disease in a mammalian subject in need thereof, the method comprising administering to the subject an inflammasome inhibitor in an amount effective to treat or prevent the ocular surface disease or damage. O’Neill, et al. teach a method of treatment of a disease, condition or disorder in a mammal and/or a human subject, comprising administering an effect of a compound of claim 1, and the compound being responsive to inhibit of activation of the NLRP3 inflammasome (see claim 30 and 32), which deems it to be an inflammasome inhibitor. O’Neill, et al. further teach the disease to be of the central nervous system including an ocular disease such as ocular epithelium which is an ocular surface disease (see claim 31). Thus, instant claim 2 is anticipated by the invention of O’Neill, et al.
Instant claim 15 recites the method of claim 2, wherein the ocular surface disease is dry eye syndrome, meibomian gland dysfunction, blepharitis, ocular rosacea allergic conjunctivitis, chemical and thermal ocular burns, Pterygium, Pinguecula, conjunctivochalasis or limbal stem cell deficiency. O’Neill, et al. teach ocular disease such as dry eye disease (see claim 31)
9. Claims 2, 15 and 19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being unpatentable over Park, et al. (Park B, Jo K, Lee TG, Hyun SW, Kim JS, Kim CS. Polydatin Inhibits NLRP3 Inflammasome in Dry Eye Disease by Attenuating Oxidative Stress and Inhibiting the NF-κB Pathway. Nutrients. 2019 Nov 15;11(11):2792. doi: 10.3390/nu11112792. PMID: 31731792; PMCID: PMC6893769).
Instant claim 2 teaches a method of treating or preventing ocular surface disease in a mammalian subject in need thereof, the method comprising administering to the subject an inflammasome inhibitor in an amount effective to treat or prevent the ocular surface disease or damage. Park, et al. teach Polydatin, which inhibits the NLRP3 inflammasome pathway, deeming it an inflammasome inhibitor (see section 3.3), was administered to six week old male rats (section 2.2), to treat dry eye disease (see section 2.2), which is an ocular surface disease. Thus, instant claim 2 in anticipated by the experiment of Park, et al.
Instant claim 15 recites the method of claim 2, wherein the ocular surface disease is dry eye syndrome, meibomian gland dysfunction, blepharitis, ocular rosacea allergic conjunctivitis, chemical and thermal ocular burns, Pterygium, Pinguecula, conjunctivochalasis or limbal stem cell deficiency. Park, et al teach polydatin inhibited NLRP3 inflammasome and thus, showed possibly specific pharmacological intervention against inflammatory disease, including dry eye disease, which is taught by instant claim 15. Park, et al. further teach that polydatin is safe to use daily treatment under its doses without any adverse side effects (see conclusion paragraph).
Instant claim 19 recites the method of claim 2, wherein the ocular surface damage is corneal staining. Park, et al. teach sodium fluorescein dye was added to the eye, and the tear film was observed under a slit lamp while the rats were prevented from blinking until tiny dry spots developed. Park, et al. further teach fluorescein score was analyzed as follows: 0, absent; 1, slightly punctate staining in less than 30 spots; 2, punctate staining in more than 30 spots, but without diffusion; 3, severe diffused staining, but without positive plaque; 4, positive fluorescein plaque. Thus, Park, et al. the ocular surface for corneal staining and this anticipates instant claim 19 (see section 2.5, ocular surface evaluation).
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.
10. Claims 2 and 15, 20, 22, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over O’Neill, et al. (US Patent No: US 11,130,731 B2, issued 09/28/2021, filed 08/07/219) in view of Niu, et al. (Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye PatientsNiu L, Zhang S, Wu J, Chen L, Wang Y (2015) Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients. PLOS ONE 10(5): e0126277. https://doi.org/10.1371/journal.pone.0126277)
Instant claim 2 teaches a method of treating or preventing ocular surface disease in a mammalian subject in need thereof, the method comprising administering to the subject an inflammasome inhibitor in an amount effective to treat or prevent the ocular surface disease or damage. O’Neill, et al. teach a method of treatment of a disease, condition or disorder in a mammal and/or a human subject, comprising administering an effect of a compound of claim 1, and the compound being responsive to inhibit of activation of the NLRP3 inflammasome (see claim 30 and 32), which deems it to be an inflammasome inhibitor. O’Neill, et al. further teach the disease to be of the central nervous system including an ocular disease such as ocular epithelium which is an ocular surface disease (see claim 31). Thus, instant claim 2 is anticipated by the invention of O’Neill, et al.
Instant claim 15 recites the method of claim 2, wherein the ocular surface disease is dry eye syndrome, meibomian gland dysfunction, blepharitis, ocular rosacea allergic conjunctivitis, chemical and thermal ocular burns, Pterygium, Pinguecula, conjunctivochalasis or limbal stem cell deficiency. O’Neill, et al. teach ocular disease such as dry eye disease (see claim 31)
O’Neill et al. do not teach elevated level of caspase 1 in a tear sample before administration step from a healthy subject, and the tear sample comprises an amount that is at least two standard errors higher than the amount of caspase-1 in the tear sample from the healthy subject
Niu, et al. teach 54 patients with Sjögren’s syndrome dry eye (SSDE), 50 patients with non-Sjögren’s syndrome dry eye (NSSDE), and 46 healthy controls were evaluated for their mRNA and protein expressions of NLRP3 inflammasome and its downstream inflammatory factors in human dry eye. Niu, et al. teach further amounts of tear IL-18 and IL-1β were measured using an enzyme-linked immunosorbent assay (ELISA) kit, which acts as a proxy for determining caspase-1 levels.
In the case of instant claim 20 and 22, elevated levels of these ILs would indicate the presence and activity of Caspase-1-mediated inflammasome, and thus, would result in determining an elevated level of caspase-1 in a tear sample and the tears were obtained from healthy subjects.
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In the case of instant claim 23, two standard errors higher is interpretated as a value that is two standard deviations away from the mean which corresponds to a p-value of 0.05. Niu, et al. teach that the IL-18 protein in the tear sample increased significant in patients non-Sjögren’s syndrome dry eye (NSSDE), at least two standards errors higher than that compared to a sample from a healthy subject. This is indicated by the chart above, in Figure 5.
The combination of treatment methodology taught by O’Neill and the diagnostic methodology Niu, et al. could reasonably combined in order to treat dry eye disease, and thus, is obvious over the instant claimed invention. One of ordinary skill in the art could reasonably incorporate the administration of a inflammasome inhibitor to treat dry eye disease, as taught by O’Neill, et al, with the diagnostic methodology for baseline measurement of elevated level of caspase-1 through a tear sample as taught Niu, et al. The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
Conclusion
11. No claims are allowed
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
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/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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