Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claim 2 has been cancelled. Claim 1 has been amended. Claims 1, 5, and 143-145 are pending and examined herein.
Cancelled/Withdrawn Rejections
The rejection under 35 U.S.C. 102(a)(1) of claims 1, 5, and 143-145 has been withdrawn in response to Applicant’s amendment.
Priority
This application, filed 01/28/2022, is a 371 of PCT/US20/43736, filed 07/27/2020, which claims benefit of PRO 62/880,479, filed 07/30/2019, and PRO 63/005,086, filed 04/03/2020.
Regarding claim 1, the inclusion of CD11c, IL23p19, CD66b, CD163, CD44, ckit, CD16, NKp46, and AHR is not found in PRO 62/880,479; therefore, this priority is not granted. This benefit to PRO 63/005,086 is acknowledged and the claims examined herein are treated as having an effective filing date of 04/03/2020.
Information Disclosure Statement
The Information Disclosure Statement filed 11/25/2025 is acknowledged and have been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 5, and 143-145 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 recites “the panel comprising two or more capture molecules…wherein each capture molecule specifically binds a marker” followed by “wherein the markers comprise one of the following sets:”. It is unclear whether the claim requires “two or more capture molecules” or capture molecules for an entire recited set of markers. For purposes of compact prosecution, the claim will be interpreted to be directed to a panel comprising capture molecules for an entire claimed set; however, appropriate correction is required. Claims 5 and 143-145 are further rejected for being dependent on claim 1.
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, 5, and 143-144 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
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. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art. See MPEP 2163.
Claim 1 recites a panel comprising “capture molecules…wherein each capture molecule specifically binds a marker polypeptide selected from the group consisting of CD3, CD4, CD5, CD24, CD25, CD27, CD3S, CD44, CD45RA, CD45RO, CD127, CD161, CTLA-4, CXCR3, CCR4, CCR6, CCR7, FOXP3, HLA-DR, IFNγ, IL-Iβ, IL-17A, IL- 21, IL-22, CD11c, IL23pl9, CD66b, CD163, CD44, ckit, CD16, NKp46, AHR, and TNFα”. Further, claim 5 recites “wherein the capture molecule is a…fragment thereof”.
The scope of the claims therefore covers the genus of each capture molecule capable of binding to the polypeptides of the claimed list, i.e. the genus of all capture molecules capable of binding to CD3, the genus of all capture molecules capable of binding to CD4, the genus of all capture molecules capable of binding to CD8, etc. Specifically, the inclusion of capture molecules for specific binding to polypeptides and fragments of these molecules lacks an adequate Written Description for the following reasons:
The specification states that “Marker expression can be detected and/or measured at the…protein level by methods well-known in the art” (p. 32, lines 15-16) and that “Marker expression can also be detected, and quantified in some embodiments, at the protein level. Antibodies that specifically bind a marker described herein or any other method known in the art can be used to monitor expression of a marker of interest” (p. 32, lines 23-25). Regarding fragments of the capture molecules, the specification recites “By ‘fragment’ is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids.” (p. 18, lines 22-26). Examiner notes that the specification lacks any description of how to determine which portions of the capture molecule could be removed to maintain the function of the claimed capture molecules.
The specification describes only the use of antibodies for each marker (Table 2 of the specification). In this case, the antibodies were used with CyTOF analysis to measure expression in patient samples.
However, the specification does not disclose any sequence or structural information about the claimed capture molecules. The specification provides no deposition certification or disclosed sequence information and lacks any specific detail about the claimed capture molecules. The structural variations that could make up capture molecules that recognize each of the claimed markers are many. Although the claims and specification describe a specific function of the claimed capture molecules, i.e. the specific binding of a marker polypeptide, the claims lack written description because there is no specific disclosure of the structure of the claimed capture molecules. Further, even if the structure and sequence of the antibodies described in the specification were provided, the specification lacks sufficient variety of species to reflect the variance in the genus of each capture molecule for binding to each claimed marker. The specification only describes possession of monoclonal antibodies to bind to the claimed markers, which is not sufficient to satisfy the Written Description requirement for the claimed genus of “capture molecules”. Moreover, the specification provides no examples of the claimed fragments of capture molecules.
The claims and specification provide no relevant identifying characteristics of the claimed capture molecules nor their functional fragments beyond their function of binding to the claimed polypeptide marker.
The specification provides no description of any methods to make the claimed capture molecules nor how to make and determine the claimed functional fragments thereof.
The level of skill in the art is high, insofar as methods for making and/or screening capture molecules were well known in the art at the time of the invention. At the same time, however, it was not within the skill of the art to reliably predict whether a particular capture molecule or fragment thereof would possess desired binding properties to a target polypeptide.
It was known that even small changes in antigen structure can profoundly affect antigen
binding interactions. For example, Harlow et al. (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26), who teach
that the loss of a single hydrogen bond can dramatically affect the ability of an antibody to recognize a cognate antigen (see especially page 26, first full paragraph). Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract). Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34). Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how a one
amino acid change in the VHCDR2 of a particular antibody was tolerated whereas, the antibody
lost binding upon introduction of two amino changes in the same region.
Moreover, at the time of the invention, it was recognized that analysis of a given amino acid sequence only provides rough guides as to whether the sequence will bind to an antibody. See Lesniewski et al. (U.S. 6,596,476 B1) at column 5, lines 40-47, who further teach that there is no invariably predictable way to ensure whether a sequence has immunological activity short of preparing the sequence and testing it in an assay.
Trial-and-error screening would be necessary to test whether any given capture molecule variant would be able to bind to the desired target polypeptide. The need to conduct further studies to determine the identities of the members of the claimed genus indicates that Applicants were not in possession of the genus at the time of filing.
The importance of structure/function correlations was recently highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Ceniocor Biologics, App. No. 2013-1338, 1346 (Fed. Cir., July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568— 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation.
Rather, the specification as above suggests performing screening to determine whether capture molecule variants would possess the requisite binding properties. While one could test a plurality of variants having different sequences to determine which, if any, have the requisite functional characteristics claimed, a “mere wish or plan” for obtaining the claimed invention is not adequate written description. See Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1566 (Fed. Cir. 1997); and Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011). This gives rise to a situation in which the actual inventive work of producing at least a substantial number of the claimed variants would be left for subsequent inventors to complete.
For these reasons, the specification does not adequately describe each of the claimed genre of capture molecules that specifically bind to each claimed polypeptide target. Examiner notes that the disclosure of the use of antibodies in the specification and the commercial availability of these antibodies does not satisfy the Written Description requirement for “capture molecules” (claim 1) or “fragment thereof” (claim 5); however, it would be sufficient for the specific use of antibodies.
Amended Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5, and 143-145 are rejected under 35 U.S.C. 103 as being unpatentable over Raine et al., “Generation of primary human intestinal T cell transcriptomes reveals differential expression at genetic risk loci for immune-mediated disease” Gut (published 05/05/2014, referred to herein as Raine) in view of Alkim et al., “The importance of peripheral immune cells in inflammatory bowel disease” Turkish Journal of Gastroenterology (published June 2007, referred to herein as Alkim) as evidenced by Affymetrix Technical Note, “GeneChip Gene 1.0 ST Array Design” (published 2007, referred to herein as Affymetrix).
Regarding claim 1, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. In order words, 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. See MPEP 2111.02 II. In this case, “for characterizing inflammatory bowel disease” is considered an intended use of the claimed panel that does not limit the structure of the panel.
Regarding claim 1, Raine teaches a panel comprising capture molecules for markers CD3, CD4, CD8, CD127, CD25, CD27, CXCR3, CCR6, CCR7, CD45, IFNγ, TNFα, IL-1β, IL-17A, IL-21, IL-22, HLA-DR, and CD38 (p. 251, col. 2, para. 3, lines 1-3, “Human Gene ST 1.0 microarray”. See Table below for Target ID on Human Gene ST 1.0 microarray).
Marker
Ensembl ID
Transcript Cluster ID
CD3
ENSG00000198851
7944179
CD4
ENSG00000010610
7953428
CD8
ENSG00000153563
8053584
CD127
ENSG00000168685
8104901
CD25
ENSG00000134460
7931914
CD27
ENSG00000139193
7953333
CXCR3
ENSG00000186810
8173493
CCR6
ENSG00000112486
8123364
CCR7
ENSG00000126353
8015031
CD45
ENSG00000081237
7908553
IFNγ
ENSG00000111537
7964787
TNFα
ENSG00000232810
8118142
IL-1β
ENSG00000125538
8054722
IL-17A
ENSG00000112115
8120210
IL-21
ENSG00000138684
8102707
IL22
ENSG00000127318
7964803
HLA-DR
ENSG00000204287
8118548
CD38
ENSG00000004468
8094240
Regarding claims 5 and 145, Raine teaches a panel (p. 251, col. 2, para. 3, lines 1-3, “Human Gene ST 1.0 microarray”) wherein the capture molecule is a polynucleotide probe complementary to the marker, as evidenced by Affymetrix (p. 1, para. 1, lines 1-6).
Regarding claims 143 and 144, Raine teaches a panel (p. 251, col. 2, para. 3, lines 1-3, “Human Gene ST 1.0 microarray”) that is a planar chip.
However, Raine does not teach a panel with markers specifically for the CD45 variants, CD45RA and CD45RO.
Alkim teaches the measurement of CD45RA and CD45RO, along with CD3, CD4, CD8 and others, in samples from patients with Crohn’s disease (Abstract lines 7-13). Alkim teaches that “CD45RA-CD45RO expressing phagocytes are important for inflammatory bowel disease and may be useful in distinguishing Crohn’s disease from ulcerative colitis” (Abstract lines 23-27).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the panel taught by Raine by adding markers for CD45RA and CD45RO to enable the characterization of CD45 variant expression in peripheral immune cells. Doing so would provide the advantage of characterizing IBD risk factors in Crohn’s Disease and ulcerative colitis patients identified in Raine. An artisan would be motivated to make this modification because, as taught by Alkim, characterization of CD45RA-CD45RO expressing phagocytes in IBD could be useful for distinguishing Crohn’s disease from ulcerative colitis. An artisan would have a reasonable expectation of success because these the characterization of these markers using capture molecules is routine and well-known in the art.
Response to Arguments
Applicant's arguments filed 11/25/2025 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on the rejection under 35 U.S.C. 112(a) of claims 1, 2, 5, 143, and 144 on pages 14 and 15, Applicant argues that the Written Description requirement has been satisfied because the application provides Examples using capture molecules and such panels of capture molecules would have been known to a person skilled in the art.
This argument is not persuasive. The Specification describes the use of antibodies in a panel for the detection of the claimed markers, which is not sufficient to describe the entire claimed genus of “capture molecules”. Further, there is no specific description of the “fragments thereof” as claimed, nor how a person skilled in the art would determine the ability of those fragments to bind to the specified markers without further experimentation.
Regarding the remarks on the rejection under 35 U.S.C. 102 of claims 1, 5, and 143-145, these arguments are considered moot due to withdrawal of the rejection due to Applicant’s amendment.
Regarding the remarks on the rejection under 35 U.S.C. 103 of claim 2, which has now been incorporated into claim 1 by Applicant’s amendment, Applicant argues that the identification of the claimed markers to differentiate between IBD patient types would not have been obvious over Raine and Alkim.
This argument is not persuasive. 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. As described regarding claim 1 above, “for characterizing inflammatory bowel disease” is considered an intended use of the claimed panel that does not limit the structure of the panel. Applicant is respectfully reminded that the pending claims are directed toward a product and not a method.
Further regarding the remarks on the rejection under 35 U.S.C. 103 of claim 2Applicant argues that neither Raine nor Alkim disclose or suggest CXCR3 as a marker on the panel.
This argument is not persuasive. As shown in the Table below (reproduced from above for Applicant’s convenience), Raine does disclose a panel comprising capture molecules for detecting CXCR3.
Marker
Ensembl ID
Transcript Cluster ID
CD3
ENSG00000198851
7944179
CD4
ENSG00000010610
7953428
CD8
ENSG00000153563
8053584
CD127
ENSG00000168685
8104901
CD25
ENSG00000134460
7931914
CD27
ENSG00000139193
7953333
CXCR3
ENSG00000186810
8173493
CCR6
ENSG00000112486
8123364
CCR7
ENSG00000126353
8015031
CD45
ENSG00000081237
7908553
IFNγ
ENSG00000111537
7964787
TNFα
ENSG00000232810
8118142
IL-1β
ENSG00000125538
8054722
IL-17A
ENSG00000112115
8120210
IL-21
ENSG00000138684
8102707
IL22
ENSG00000127318
7964803
HLA-DR
ENSG00000204287
8118548
CD38
ENSG00000004468
8094240
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 January 6, 2026