DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-4, 6, 8, 9 and 11-15, in the reply filed on 4/9/26 is acknowledged.
Claims 16-18 and 21-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claim Objections
Claims 6 and 11 are objected to because of the following informalities:
Claim 6 depends from canceled claim 5.
In claim 11, the members of the Markush group should be separated by commas not semicolons. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because it claims a naturally occurring protein which exists in nature. The claimed protein is not markedly different from what naturally exists in nature. Even though isolation structurally changes a protein from its natural state, the resultant difference is no enough to render the isolated protein markedly different because the genetic structure and amino acid sequence of the protein has not been altered. The term “immunogenic composition” is an intended use only. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the naturally occurring protein in order to patentably distinguish it. The “pharmaceutically acceptable carrier” is an “optional” ingredient; however, even if it were to be amended as a required element, the term reads on water which would naturally occur and not change the structure or function of the protein composition. See Myriad, 133 S.Ct. at 2166-18.
Claim Rejections - 35 USC § 112-2nd paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 6, 8, 9 and 11-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is vague and indefinite because a name alone “Salmonella Enteritidis protein InvG” to identify the protein is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. The claim should provide any structural properties, such as the amino acid sequence of the protein, which would allow for one to identify the protein without ambiguity. The mere recitation of a name or general function does not adequately define the claimed protein. The metes and bounds of these claims cannot be understood. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim 1, 3, 4 and 6 are vague and indefinite due because the term “optionally” makes it unclear if the optional elements are part of the claim for patent protection purposes. See MPEP 2173.05(h). Appropriate clarification and/or correction is required.
Claim 2 is vague and indefinite due to the terms “a variant” and “an immunogenic fragment” of SEQ ID NO: 2. It is unclear how the polypeptides ‘vary’ or what the ‘variant’ sequence comprises and if the variant is of function or sequence or both. With respect to the immunogenic fragments thereof, these can read on as few as 3-5 amino acids. The structure of the variants and fragments are unclear so the metes and bounds of the invention are not readily understood. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim 3 recites a composition for inducing an immune response comprising an “organism engineered to express “Salmonella Enteritidis protein InvG”, but provides no technical features for this function. The claim is vague and indefinite because it does not provide adequate description. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim 6 lacks antecedent basis for the term “the E. coli.” As noted in the ‘claim objections’ above, claim 6 depends from canceled claim 5 and claims 3 and 4 do not have or require that the organism be an “E. coli.” Appropriate clarification and/or correction is required.
Claim 6 is also vague and indefinite because it is unclear what structure comprises any “avirulent mutation”. The structures encompassed by this term are not readily understood and the metes and bounds of the invention are unclear. Additionally, SEQ ID NO: 3 is not required by the claim and it the use of the term “optionally comprises” is unclear in this context. Appropriate clarification and/or correction is required.
Claim 8 is vague and indefinite because it does not recite that the expression vector is inside the cell. It is also vague and indefinite due to the terms “a variant” and “an immunogenic fragment” of SEQ ID NO: 2. It is unclear how the polypeptides ‘vary’ or what the ‘variant’ sequence comprises and if the variant is of function or sequence or both. With respect to the immunogenic fragments thereof, these can read on as few as 3-5 amino acids. The structures of the variants and fragments are unclear so the metes and bounds of the invention are not readily understood. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim Rejections - 35 USC § 112-Scope of Enablement
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 1-4, 6, 8, 9 and 11-15 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:
An immunogenic composition comprising an immunogenically effective amount of a purified Salmonella Enteritidis protein InvG and an adjuvant;
A composition for inducing an immune response against Salmonella Enteritidis comprising a recombinant E. coli with an expression vector comprising the nucleic acid sequence of SEQ ID NO: 4.
And methods for inducing an immune response in poultry using either of these compositions,
does not reasonably provide enablement for:
Immunogenic compositions or vaccine compositions comprising any fragments or variants from SEQ ID NO: 2 InvG protein of Salmonella Enteritidis or any organisms engineered to express Salmonella Enteritidis comprising any expression vector; or any methods using these fragments/variants/cells.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The instant specification teaches vaccination with full-length protein InvG elicited strong systemic antibody responses in hens, allowed efficient maternal transfer of IgY and mucosal IgA to progeny, and reduced intestinal colonization by heterologous Salmonella serovars in newly hatched chicks. The instant specification also teaches An E. coli-vectored vaccine expressing InvG [which has the expression vector comprising the nucleic acid sequence of SEQ ID NO: 4].
See the specification, for example:
Example 1: The immunogenicity and efficacy of InvG protein of Salmonella Enteritidis against a challenge of S. Enteritidis in chickens. In this example, immunogenicity of the protein and efficacy against a homologous challenge is assessed. Newly hatched chicks are randomly divided into three groups of 20 chickens. Chickens in group 1 are vaccinated intramuscularly with 50 µg of InvG and 50 µg of Quil-A at days 14 and 28 days of age. The chickens are challenged with 10¹⁰ CFU of S. Enteritidis strain SEE1 in 0.5 ml of phosphate buffered saline administered orally at 35 days of age. Five birds from each group are sacrificed on day 2, 7, 14, and 21 post-challenge. Liver, spleen, and cecal contents are collected at necropsy for Salmonella culture and enumeration.
Example 2: Antibodies against InvG can transfer passively from vaccinated hens to progeny chickens thus providing protection. In this example, layer chickens are vaccinated with InvG, and the eggs laid by the vaccinated hens and their progeny chicks are monitored for anti-InvG and sIgA antibodies. One- day-old progeny chicks are also challenged with S. Enteritidis to assess the protection provided by passively transferred antibodies.
Example 3: to minimize colonization of chicken intestines and ovaries by nontyphoidal Salmonella. Chicken challenge An E. coli-vectored vaccine expressing InvG [expression vector comprising the nucleic acid sequence of SEQ ID NO: 4] experimental approach will be similar to the approach described under the example 2 (FIG 13 and 14) except that the chickens are vaccinated with 1x10⁷ CFU/ml of bacteria in PBS inoculated orally twice (day 14 and 28) in place of four-dose recombinant protein antigen vaccination regimen. Challenging chickens with S. Enteritidis, S. Typhimurium, S. Heidelberg, and S. Branenderup, measurement of anti-InvG antibodies in the chicken sera, intestinal washings, and eggs, and collection of tissues, bacterial culture is performed as described under the example 2. Appropriate negative and positive controls are used.
However, the scope of the instant claims encompasses the use of any immunogenic fragments and variants of any kind from SEQ ID NO: 2. The instant specification recites on page 19, lines 14-20:
As noted, immunogenic fragments and variants of S. enterica InvG protein are described and may be administered to a poultry subject. Such immunogenic fragments can comprise at least about 5, at least about 10, at least about 15, at least about 20, at least about 50, at least about 60, at least about 80, at least about 100, at least about 150, at least about 200, at least about 300, at least about 400, at least about 500, at least about 600, at least about 700, at least about 800, at least about 900, at least about 1,000 contiguous amino acid residues or up to the entire contiguous amino acid residues of the InvG protein (e.g. SEQ ID NO:2).
The specification states that substitutions, additions, or deletions, may be made to the defined sequences; however, the specification provides no guidance as which amino acids may be changed without causing a detrimental effect to the InvG protein and with the added immunogenic function requirement. It is unpredictable as to which amino acids could be removed and which could be added. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein’s sequence where amino acid substitutions can be made with a reasonable expectation of success are limited. Other positions are critical to the protein’s structure/function relationship, e.g., such as various positions or regions directly involved in binding, catalysis in providing the correct three-dimensional spatial orientation of binding and catalytic sites. These regions can tolerate only very little or no substitutions. Selective point mutation to one key residue could eliminate the function of the polypeptide. It could eliminate its functional properties. If the range of decreased binding ability after single point mutation of a protein antigen varies, one could expect point mutations in the protein antigen to cause varying degrees of loss of protection/function, depending on the relative importance to the binding interaction of the altered residue. Alternatively, the combined effects of multiple changes, as instantly claimed, in an antigenic determinant could again result in loss of function. A protein having multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable. As stated above, Applicants have not shown the particular substitution and the result it produces. Applicants have provided no guidance to enable one of ordinary skill in the art how to determine, without undue experimentation, the effects of different amino substitutions and the nature and extent of the changes that can be made. It is expensive and time consuming to make amino acid substitutions at more than one position, in a particular region of the protein, in view of the many fold possibilities for change in structure and the uncertainty as to what utility will be possessed. See Mikayama et al. (Nov.1993. Proc.Natl.Acad.Sci. USA, vol. 90 : 10056-10060) which teaches that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Rudinger et al. (June 1976. Peptide Hormones. Biol.Council. pages 5-7) also teaches that amino acids owe their ‘significance’ to their inclusion in a pattern which is directly involved in recognition by, and binding to, the receptor and the significance of the particular amino acids and sequences for different amino acids cannot be predicted a priori, but must be determined from case to case by painstaking experimental study. The instant claims allow for substitutions with amino acids of vastly different properties and they do not recite the specific changes in the claims.
The examples in the specification only teach use of the full-length protein and E.coli expressing said protein. There are no examples of any particular fragments or portions of the protein which would confer the same immunogenic effect. For the reasons stated above, it would be unpredictable and take undue experimentation to determine and discover variants and fragments with the same effect.
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
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)(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.
Claim(s) 1, 3 and 4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crago et al (Molecular Microbiology, 1998, 30(1): 47-56; provided by Applicants).
Crago discloses Salmonella protein InvG (To examine the secretion process in Salmonella, we expressed InvG in laboratory Escherichia coli; page 47, column 2, paragraph 2). With respect to the optional pharmaceutically acceptable carrier in claim 1, “pharmaceutically acceptable carrier” reads on water and therefore would be inherent in the preparation of the cells. With respect to the composition of the cell having the capability to “populate in a poultry subject,” a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. This ability would be inherent to engineered cells of Cargo since they are structurally identical. A “physiologically acceptable carrier” reads on water and therefore would be inherent in the preparation of the mutants.
Claim(s) 1, 3, 4, 6, 9 and 11-15 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Thanos et al (WO 2020/176809 A1, 9/3/2020; provided by Applicants).
As per claim 1, Thanos discloses an immunogenic composition (composition described in method for immunological intervention through immunogenic responses (immunogenic composition); page 194, lines 26-28) that comprises: an immunogenically effective amount of a Salmonella Enteritidis protein InvG (complex introduced into host cells at effective amount including salmonella island proteins including InvG; page 100; lines 13-15; page 101, lines 1-5; page 119, line 2; page 201, lines 9-11), and optionally a pharmaceutically acceptable carrier (complex comprises pharmaceutically acceptable excipients; page 190; lines 24-26).
With respect to instant claims 9 and 11, Paragraph [0321] teaches administering to animals which include: any animal, such as, but not limited to, primates including humans, gorillas and monkeys; rodents, such as mice and rats; fowl, such as chickens; ruminants, such as goats, cows, deer, sheep; pigs and other animals. Non-human animals exclude humans as the contemplated animal. The polypeptides provided herein are from any source, animal, plant, prokaryotic and fungal. Most polypeptides are of animal origin, including mammalian origin.
As per claim 3, Thanos discloses a composition for Inducing an immune response against Salmonella Enteritidis (composition disclosed leading to immunological intervention (immune response) against bacteria such as Salmonella Enteritidis; page 119, line 2; page 194, lines 26-28) comprising an organism engineered to express Salmonella Enteritidis protein InvG (host cell designed to include InvG protein derived from Salmonella Enteritidis; page 5, lines 12-15; page 100; lines 13-15; page 101, lines 1-5; page 119, line 2), and optionally a pharmaceutically acceptable carrier (complex comprises pharmaceutically acceptable excipients; page 190; lines 24-26).
Per claim 6, Thanos teaches the use of avirulent bacteria. See “Bacterial attenuation” on pages 78-88. As noted in the 112, second paragraph rejection set forth above, claim 6 depends from canceled claim 5 and claims 3 and 4 do not have or require that the organism be an “E. coli.”
As per claim 13, Thanos discloses the further comprising an adjuvant (compositions can include carriers such as adjuvants; page 196, lines 21-22).
With respect to instant claim 15, since the method step and product are the same, the method would inherently comprise an immunogenic response against any of the recited Salmonella spp.
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.
Claim(s) 2 and 8, as applied to claims 1, 3, 4, 9 and 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thanos et al (WO 2020/176809 A1, 9/3/2020; provided by Applicants) in view of Jayasinghe et al (WO 2018/146491, 8/16/18; provided by Applicants).
The teachings of Thanos are set forth above; however, Thanos does not disclose wherein said Salmonella Enteritidis protein InvG comprises a polypeptide sequence comprising SEQ ID NO. 2 or immunogenic fragments or variants thereof as recited in instant claims 2 and 8.
Jayasinghe discloses wherein said Salmonella Enteritidis protein InvG comprises a polypeptide sequence comprising SEQ ID NO. 2 or immunogenic fragments or variants thereof (SEQ ID NO:2 of the instant application is 100% identical to SEQ ID NO: 2 of Jayasinghe; page 8, lines 13-14). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the InvG protein of Thanos to include SEQ ID NO: 2, as taught by Jayasinghe, because SEQ ID NO: 2 corresponds to sequence which is InvG without N1 or NO domains are can be utilized in polypeptides (Jayasinghe; page 1, lines 21-24).
As per claim 8, Thanos discloses does not disclose wherein said Salmonella Enteritidis protein InvG is cloned into an expression vector that is engineered to express SEQ ID NO. 2 or immunogenic fragments or variants thereof. Jayasinghe discloses wherein said Salmonella Enteritidis protein InvG is cloned into an expression vector (Salmonella enterica InvG protein cloned into expression vector; page 8, lines 13-14; page 38, lines 1) that is engineered to express SEQ ID NO. 2 or immunogenic fragments or variants thereof (SEQ ID NO:2 of the instant PCT application is 100% identical to SEQ ID NO: 2 of Jayasinghe; page 1, lines 21-23). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the InvG protein of Thanos to include SEQ ID NO: 2, as taught by Jayasinghe, because SEQ ID NO: 2 corresponds to sequence which is InvG without N1 or NO domains are can be utilized in polypeptides (Jayasinghe; page 1, lines 21-24). As per claims 29/2 & 29/8, Thanos and Jayasinghe, in combination, disclose the composition of any of claims 2 & 8, and Thanos further discloses further comprising an adjuvant (compositions can include carriers such as adjuvants; page 196, lines 21-22). respect to instant claim 15, since the method step and product are the same, the method would inherently comprise an immunogenic response against any of the recited Salmonella spp.
Sequence Compliance
It is noted that Table 1 on page 12 of the instant specification recites nucleotide/amino acid sequences which are encompassed by the definitions for nucleotide sequences as set forth in 37 C.F.R. 1.821(a)(1) and (a)(2). The M.P.E.P., Section 2422.02, 37 CFR 1.821(b) requires exclusive conformance, with regard to the manner in which the nucleotide/amino acid sequences are presented and described, with the sequence rules for all applications that include nucleotide sequences that fall within the definitions.
APPLICANT MUST COMPLY WITH THE SEQUENCE RULES WITHIN THE SAME TIME PERIOD AS IS GIVEN FOR RESPONSE TO THIS ACTION, 37 C.F.R. 1.821-25. Failure to comply with these requirements will result in ABANDONMENT of the application under 37 C.F.R. 1.821(g). Extensions of time may be obtained by filing a petition accompanied by the extension fee under the provisions of 37 C.F.R. 1.136. In no case may an applicant extend the period for response beyond the six-month statutory period.
Status of claims:
No claims are presently allowed.
The InvG protein from Salmonella Enteritidis has long been known in the prior art, as evidenced by the prior art teachings. Additionally, cells engineered to recombinantly express said InvG protein were also well known.
NOTE: Claims 1-4, 6 and 8 are drawn to compositions claims/products. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. A patent for a new method/use of a known product may be obtained, but a patent cannot be obtained for a known product, e.g., when the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process. In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986). The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957).
Prior art, not presently relied upon:
Donati et al (WO 2007/072214-A2). Type III secretion system protein SEQ ID NO:42 is 100% identical to Applicants’ SEQ ID NO: 2.
Paas et al (WO2011125015-A2). Protein engineering; BOND_PC; invG. 99.9% identical to SEQ ID NO: 1.
Parkhill et al (Nature 413, 848-852, 2001) Salmonella enterica subsp. enterica serovar Typhi (strain CT18). Protein 100% identical to Applicants’ SEQ ID NO: 2.
Wang et al (CN105969782-A) FRT DNA polynucleotide fragment SEQ: 12- fragment 73.8% identical to Applicants’ SEQ ID NO: 3.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached at (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 5/21/26
Prosecution Insights