DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, claims 19-22, 25, 30, 41 and 42, in the reply filed on 9/25/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 29, 31-34, 36 and 41-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Specification
The disclosure is objected to because of the following informalities: the specification contains Dutch language on page 37, e.g.,
“Fout! Verwijzingsbron niet gevonden” at lines 4 and 14.
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.
Claims 19, 21, 22, 25, 41 and 42 are rejected under 35 U.S.C. 101 because is directed to non-statutory subject matter because the claims are drawn to an isolated polypeptide which exists in nature, e.g., a naturally occurring variant. On pages 3 and 4 of the instant specification, it is disclosed that the inventors have identified a distant variant of the polypeptide Amuc-1100. Applicants have recited the polypeptide comprising SEQ ID NO: 5, used in all of the examples, is a naturally occurring variant. The claimed polypeptide is not markedly different from what naturally exists in nature. Even though isolation structurally changes a polypeptide from its natural state, the resultant difference is no enough to render the isolated polypeptide markedly different because the genetic structure and sequence of the nucleic acid has not been altered. See Myriad, 133 S.Ct. at 2166-18. The composition comprises a polypeptide and a pharmaceutically acceptable or alimentary acceptable carrier. A recitation of the intended use, e.g., pharmaceutical composition, 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 “physiologically acceptable carrier” reads on water and therefore would be inherent in the naturally occurring peptides.
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 19-22, 25, 30, 41 and 42 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.
Claims 19, 21, 22, 41 and 42 recite “or conservative substitutions thereof”. However, by “conservative substitutions”, it is not known what amino acids are to be substituted, and thus the claimed invention is unclear. Paragraph [0088] in the specification has an explanation of the term “conserved substitutions”. Even if this is considered to define "conservative substitutions", the relevant paragraph states “as used herein may refer to replacement of one or more amino acids in a polypeptide without substantial loss of functionality”, which can also be interpreted to mean simply an example. Furthermore, in cases where a substitution is to be made “without substantial loss of functionality”, the specific amino acids suitable for such substitution can only be determined by actually performing the substitution and verifying the function thereof. Therefore, even with reference to the relevant paragraph, it is unclear which amino acid substitutions correspond to “conservative substitutions”. Additionally, 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.
Claim 19 is also vague and confusing because the actual structure being claimed has a low 25% sequence identity to SEQ ID NO: 5 with conservative substitutions and the requirement of no more than 92% to SEQ ID NO: 1 which makes the structure covered by the claims vague and confusing. The use of two different reference sequences with such a large breadth of different structure/substitutions makes the metes and bounds of the invention unclear. Additionally, the specification appears to show the invention as SEQ ID NO: 5 and the results in the Examples are obtained with SEQ ID NO: 5 so it is unclear which structure with all the various substitutions and identity requirements 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 19-22, 25, 30, 41 and 42 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:
A composition comprising an isolated polypeptide and a pharmaceutically acceptable carrier, wherein the isolated polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 5. wherein the polypeptide affects immune signaling, affects intestinal barrier function, affects glucose homeostasis, cholesterol homeostasis, and/or triglyceride homeostasis.
, does not reasonably provide enablement, for example:
A composition comprising an isolated polypeptide (a) has at least 25% sequence identity with SEQ ID NO:5, (b) has F, E, V, Y, and R or conservative substitutions thereof at positions that correspond to positions 122, 123, 145 to 147 respectively in SEQ ID NO:5, and (c) does not have more than 92% sequence identity with SEQ ID NO:1; the composition of claim 19, wherein the isolated polypeptide comprises the following sets of amino acid residues: (a) W, L, G, and F or conservative substitutions thereof at positions that correspond to positions 101, 102, 103, and 104 respectively in SEQ ID NO:5; (b) F and E or conservative substitutions thereof at positions that correspond to positions 122, and/or 123 respectively in SEQ ID NO:5; and/or (c) V, Y, and R or conservative substitutions thereof at positions that correspond to positions 145, 146, and 147 respectively in SEQ ID NO:5. 42, wherein the polypeptide affects immune signaling, affects intestinal barrier function, affects glucose homeostasis, cholesterol homeostasis, and/or triglyceride homeostasis.
The composition of claim 19, wherein the isolated polypeptide comprises the following sets of amino acid residues: i. R, S, I, S, A, and P or conservative substitutions thereof at positions that correspond to positions 6, 7, 13, 22, 25, and 30 respectively in SEQ ID NO:5; il. C, K, K, I, and T or conservative substitutions thereof at positions that correspond to positions 88, 89, 91, 93, and 96 respectively in SEQ ID NO:5; iii. W, L, G, and F or conservative substitutions thereof at positions that correspond to positions 101, 102, 103, and 104 respectively in SEQ ID NO:5; iv. F and E or conservative substitutions thereof at positions that correspond to positions 122, and/or 123 respectively in SEQ ID NO:5; Vv. V, Y, and R or conservative substitutions thereof at positions that correspond to positions 145, 146, and 147 respectively in SEQ ID NO:5; vi. P, E, I, F, Q, R, S, and V or conservative substitutions thereof at positions that correspond to positions 174, 176, 177, 179, 180, 183, 185, and 186 respectively in SEQ ID NO:5; and/or Vil. P, P, P, A, A, P, G, T, A, E, A, P, Q, K, G, and E or conservative substitutions thereof at positions that correspond to positions 215, 217, 221, 222, 223, 226, 234, 239, 241, 243, 245, 250, 253, 257, 261, and 263 respectively in SEQ ID NO:5.
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.
On pages 3 and 4 of the instant specification, it is disclosed that the inventors have identified a distant variant of the polypeptide Amuc-1100 in Akkermansia glycaniphila which is capable of modulating and/or promoting the gut immune system function and/or maintaining and/or restoring and/or increasing the physical integrity of the 30 gut mucosal barrier, and/or of maintaining and/or restoring and/or improving glucose and/or cholesterol and/or triglyceride homeostasis in a mammal (e.g. human). This is surprising, since previous research reports that Akkermansia glycaniphila does not have a homolog of Amuc-1100 (see Xing et al (2019; Genes & Genomics 41:1253-1264; provided by Applicants). The inventors teach it is a result from the ability to interact with the TLR2 signaling pathway present at the surface of immune cells located in the vicinity of the gut mucosal barrier of a mammal. More specifically, the present inventors found that the polypeptide as taught herein is capable of interacting with the TLR2 present at the surface of an immune cell and/or modulating and/or stimulating the TLR2-signaling pathway in an immune cell located in the vicinity of the gut mucosal barrier, so as to stimulate the secretion of cytokines (e.g. IL-6, IL-8, and IL-10) from said immune cells. Further, the present inventors found that the polypeptide as taught herein, is capable of modulating and/or increasing the transepithelial resistance of the gut mucosal barrier of a mammal. Since increased transepithelial resistance measurement serves as an index of decreased permeability of the gut mucosal barrier, it is believed that the polypeptides, including variants thereof, as taught herein are capable of modulating the physical integrity of the gut mucosal barrier, particularly at the level of the tight junctions between epithelial cells. Combined together, these effects are believed to result in an improved or increased gut mucosal immune system function (e.g. greater release of cytokines at the gut mucosal barrier) as well as improved or increased physical integrity of the gut mucosal barrier, particularly at the level of the connection between gut epithelial cells (i.e. via tighter tight junctions between cells).
According to the specification, six polypeptides were actually prepared in the present application: Amuc-1100, pTH008, pTHO09, pTH010, pTHO11, and pTH012, their amino acid sequences being SEQ ID NO: 1 and SEQ ID NOs: 5-SEQ ID NO: 9, respectively. The technical effects, such as the interaction between the six polypeptides mentioned above and the TLR2 signaling pathway, their stimulation of peripheral blood mononuclear cells to release cytokines, their regulation of transepithelial resistance, and their regulation of diet-induced metabolic dysfunction in C57BL/6J mice, were verified, the sequence structures of Amuc-1100, pTH008, pTH009, pTHO10, pTHO11, and pTHO12 were compared, and the relationship between specific conserved regions and the ability to activate LTR2 was examined. Polypeptides mentioned above all have specific amino acid sequences, and the amino acid sequences of these polypeptides should be defined in a closed manner.
However, according to the fully disclosed content of the description and the prior art, a person skilled in the art cannot predict whether other polypeptides defined in claim 19, besides the verified polypeptides mentioned above, can also solve the technical problems described in the present application and achieve the same or similar technical effects. The instant specification only shows the effects, i.e., immune signaling, affects intestinal barrier function, affects glucose homeostasis, cholesterol homeostasis, and/or triglyceride homeostasis for the polypeptides represented by SEQ ID NO: 5 and not the full breadth of the claims. The instant claims include many with low sequence identity, e.g., at least 25% identical to SEQ ID NO:5, and many different conservative substitutions some which are not specifically recited, e.g., other conservative substitutes thereof. Many of the peptides in the claims have multiple substitutions and it cannot be recognized that they achieve the same effects as those shown for the polypeptide of SEQ ID NO: 5.
Natural variants: four proteins were identified in related A. muciniphila strains with an amino acid identity above 80 % to the Amuc_1100 protein of Amuc'’ (pTHO08, SEQ ID NO:5, pTHOO9, SEQ ID NO:6, pTHO10, SEQ ID NO:7, pTHO11, SEQ ID NO:8). Additionally, a more distant variant from Akkermansia glycaniphila with only 28% sequence identity was identified (PTHO12, SEQ ID NO:9). These 5 proteins the inventors refer to as natural variants of Amuc_1100. Table 2 and Figure 2 show conserved residues in the studied natural variants.
The results in the specification show that Amuc-1100 was able to interact with TLR2. Further, the results show that Amuc-1100 exerted immune-stimulatory effects on reporter cells expressing TLR2, i.e. Amuc-1100 was capable of stimulating the release of NF-kB from reporter cells. Similar results were obtained with the polypeptide of SEQ ID NO:5.
Independent claim 19 recites an isolated polypeptide that can promote gut mucosal immune system function, anti-inflammatory activity in the gut, and weight reduction in mammals and as these polypeptides, (a) has at least 25% sequence identity with SEQ ID NO:5, (b) has F, E, V, Y, and R or conservative substitutions thereof at positions that correspond to positions 122, 123, 145 to 147 respectively in SEQ ID NO:5, and (c) does not have more than 92% sequence identity with SEQ ID NO:1. The sequence identity specified in (a) is as low as 25% and encompasses sequences with less than 90% identity. Also, (b) specifies only five specific amino acid positions, and the types of amino acids are unclear due to being specified by the recitation “conservative substitutions”. As a result, it is recognized that the present invention encompasses polypeptides consisting of various sequences. Meanwhile, the only polypeptides specifically disclosed in the present specification together with experimental results are those consisting of the amino acid sequences shown in SEQ ID NOs:5 to 9. Polypeptides consisting of other sequences are neither specifically disclosed nor suggested.
Generally, as sequence identity between polypeptides decreases, there is a higher likelihood that their functions or properties will significantly differ. The fact that only five amino acid residues remain unchanged or are subject to conservative substitution does not necessarily ensure that the resulting polypeptide retains the same functions or properties as the original polypeptide. Also, it is common technical knowledge of a person skilled in the art that it is difficult to predict from sequences, functions, etc. as to polypeptides consisting of what sequences would have the same functions or properties as the original polypeptide. Furthermore, even if there is high sequence identity to SEQ ID NO: 5, considering that, for example, the effects of polypeptides having the amino acid sequences of SEQ ID NO: 5 to 8, which have high sequence identity to SEQ ID NO: 1, significantly differ for TLR2 activation, it is recognized that it is highly likely that the functions or properties of obtained variants will vary substantially depending on the positions and types of amino acid substitutions. Therefore, a person skilled in the art who knows of the disclosures in the specification of the present application would not be able to infer what other polypeptide sequences, apart from those consisting of the amino acid sequences of SEQ ID NOs:5 and all of the numerous variants in subsequent claims 21, 22, 41 and 42, would result in polypeptides having gut mucosal immune system function etc., and it is recognized excessive trial and error would be required to do so. The specification states that substitutions 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 polypeptide and the recited functional requirements. 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. The combined effects of multiple changes, as instantly claimed could 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 instant specification and claims include many polypeptides with low sequence identity and it cannot be recognized that by having only the amino acids specified in claims necessarily achieves the same effects as those shown for the polypeptides of SEQ ID NOs: 5 -9.
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.”
Given the complexity of the art, the breadth of the claims, the number of potential mutations, and the lack of guidance provided by the applicant, the examiner finds that there is insufficient information in the specification to enable those skilled in the art to practice the claimed invention without undue experimentation.
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) 19-22, 25, 30, 41 and 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Belzer et al (WO 2016/177797; provided by Applicants); Accession No. WP_067981703 (Definition: MULTISPECIES: hypothetical protein [unclassified Akkermansia], GenBank [online], 13-DEC-2019 uploaded; provided by Applicants); and Accession No. AOAIC7P913 (Definition: Uncharacterized protein, Database UniProtKB [online], 11-DEC-2019 uploaded; provided by Applicants).
NOTE: The instant claims allow for any ‘conservative substitutions thereof” and the claims are interpreted with this breadth.
Belzer et al (claims and examples) discloses: an isolated Amuc-1100 polypeptide which has at least 50% sequence identity to the amino acid sequence of SEQ ID NO:1, and which promotes gut mucosal immune system function, anti-inflammatory activity in the gut, and weight reduction in mammals; a host cell comprising a nucleic acid encoding the polypeptide; Akkermansia muciniphila can be selected as the host cell; and compositions such as pharmaceuticals and foods comprising the polypeptide.
Belzer differs in that it does not specifically recite an isolated polypeptide in which the amino acids corresponding to positions 122, 123, and 145 to 147 of SEQ ID NO:5 is maintained or conservatively substituted and which does not have more than 92% sequence identity to SEQ ID NO:1.
However, Accession No. WP_067981703 recites the amino acid sequence of a naturally occurring Amuc-1100 polypeptide derived from the genus Akkermansia (see: ORIGIN section). This polypeptide has amino acids at the positions specified in instant claim19 of the present application and has 77% sequence identity to Applicants’ SEQ ID NO:5 (when analyzed using Clustal W, 70.1% same by EMBOSS Needle) and 81% sequence identity to SEQ ID NO:1 of the present application (when analyzed using Clustal W, 73.3% same by EMBOSS Needle). This polypeptide has amino acids at the positions specified in claims of the present application and has 77% sequence identity to SEQ ID NO:5 of the present application (when analyzed using Clustal W, 70.1% same by EMBOSS Needle) and 81% sequence identity to SEQ ID NO:1 of the present application (when analyzed using Clustal W, 73.3% same by EMBOSS Needle). Therefore, a person skilled in the art could easily conceive of attempting to employ the polypeptide disclosed by Accession No. WP_067981703, which is known as a naturally occurring Amuc-1100 polypeptide derived from the genus Akkermansia, in the invention disclosed by the Belzer. It is noted in the instant specification that the effects for the polypeptides represented by SEQ ID NOs: 5-9 are shown and the effects for polypeptides consisting of other sequences are not specifically shown.
Accession No. AOAIC7P913 discloses a polypeptide derived from Akkermansia glycaniphila. Although this reference does not specifically disclose that the polypeptide “effects immune signaling and/or affects intestinal barrier function and/or affects glucose and/or cholesterol and/or triglyceride homeostasis”, considering that it consists of the same sequence as SEQ ID NO:9 in the examples of the present application, it is recognized to naturally have these properties and characteristics. For a known polypeptide with unknown functions or properties, it is routine practice for a person skilled in the art to construct a host cell comprising a nucleic acid molecule encoding said polypeptide in order to investigate its functions or properties, and furthermore, to use the obtained host cell to produce the polypeptide. Accordingly, a person of ordinary skill in the art could easily conceive of employing, a host cell similar to that of the claim 20, as well as a method for producing a polypeptide using such host cell. 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 “pharmaceutically acceptable or alimentary acceptable carrier” reads on water and therefore would be inherent in the preparation of the polypeptides. Given the same structure, the peptides would inherently possess the same functions.
Prior art not presently relied upon:
Huang et al (US Patent No. 11,666,629; priority filing date 1/10/20) teaches a polypeptide which is 96.3% identical to Applicants’ SEQ ID NO: 5 (See SEQ ID NO: 1) It is: as defined herein, Amuc_1100 refers to the full length of protein Amuc_1100, which can be obtained from common databases; Amuc_1100* defined herein refers to the protein Amuc_1100 which does not include the transmembrane domain thereof and is presented herein as SEQ ID NO: 1.
Zhang M. et al ("GSP:BHR36684; A. muciniphila Amuc-1100 variant (L68R/L72E/Y75E/ A76R/V79E/L217R).", 3 April 2020 (2020-04-03), XP055781928, Retrieved from the Internet: URL:http://ibis.internal.epo.org/exam/dbfetch.jsp?id=GSP:BHR36684 [retrieved on 2021-03-04], & CN 110 950 937 A (UNIV ANHUI) 3 April 2020; provided by Applicants);
discloses an Akkermansia municiphila variant Amuc-1100 protein showing 33.2% sequence identity to SEQ ID NO: 9 and comprising the corresponding amino acid residues detailed in claims. Moreover, the use of said protein for medicinal preparations for improving human intestinal functions is disclosed (see appended CN publication). The reference teaches a polypeptide with an amino acid sequence 96.3% identical to Applicants’ SEQ ID NO: 5 and identified as crystal structure of monomeric Amuc_1100 from Akkermansia muciniphila.
Zang et al (CN111690044-A; Sept. 22, 2020; corresponding to Accession No. BIG42608). Akkermansia muciniphila ATCC BAA-835 1100 mature protein, SEQ ID NO: 2 which is 96.3% identical to Applicants’ SEQ ID NO: 5.
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-Thursday from 8:00 AM-6:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gary Nickol, can be reached on (571) 272-0835.
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 10/15/25