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 .
DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group V (claims 32-33) in the reply filed on 2/20/26 is acknowledged. The traversal is on the ground(s) that the cited references of (Li et al., Lab on a Chip, 20(6), 1072-1082 and Sidney et al., Current Protocols in Immunology, 100 pages 18.3.1-18.3.36) do not disclose the combined features of utilizing an anti-MHC antibody to draw down pMHC complex, extracting the pMHC complex from the sample and then comparing the MHC presented peptide with a library of pathogen-derived antigens to determine if said peptide shows homology/affinity with at least one pathogen-derived antigen, or part thereof, and where greater than 60% homology/affinity exists. Therefore because the claims of Groups I-V are characterized by the same feature, Applicants submits that the inventions of Groups I-V are unified and respectfully request withdrawal of the Restriction Requirement.
This argument was carefully considered but is not found persuasive because Groups I-V are not characterized by the argued same feature. In particular, the method of Group I (claims 1-8) has six steps and merely identifies a peptide as a tumor antigen for use in cancer therapy but does not administer a treatment. Group II (claims 9-16) is drawn to a device and processor.
While, the treatment methods of Group III (claim 29), Group IV (claim 31), and Group V (claims 32 and 33) have eight method steps but differ in the administered treatment. Group III administers an ICI, Group IV administers an adenoviral vector, and Group V administers T-cells.
The recited Groups (I-V) appear to require the technical feature of a microfluidic device comprising micropillars arranged in an array with an anti-MHC antibody, this technical feature is not a special technical feature as it does not make a contribution over the prior art.
Applicant contends that the cited references do not disclose the combined features of utilizing an anti-MHC antibody to draw down pMHC complex. However, the prior art has taught the specific binding pair between anti-MHC antibodies and pMHC to form a complex involving anti-MHC antibody + pMHC. See Sidney et al., Current Protocols in Immunology, 100 pages 18.3.1-18.3.36). Therefore, absent evidence to the contrary; it would have been obvious to immobilize either member of the binding pair to detect the corresponding specific binding member (using either anti-MHC antibody or pMHC to drawn down pMHC or anti-MHC antibodies respectively) in a sample.
3. The requirement is still deemed proper and is therefore made FINAL.
4. Claims 1-16, 29, and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/20/26. Currently claims 32 and 33 are under consideration.
Priority
5. The instant application has a priority date of May 7, 2020. This is the U.S. National Stage of International Application No. PCT/EP2021/061981, filed May 6, 2021, which was published in English under PCT Article 21 (2), which claims the benefit of GB Application No. 2006760.9, filed May 7, 2020.
Information Disclosure Statement
6. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered.
7. The Information disclosure Statements (IDS) filed on 11/4/22 and 11/8/22 have been considered as to the merits before the First Action.
Specification
8. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. For example, see page 8 lines 20-21, page 28 line 25, page 35 line 12, and page 37 line 13.
Abstract
9. Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
10. The abstract utilizes legal phraseology. See “said” – Appropriate correction is required.
Claim Objections
11. Claims 32 and 33 are objected to because of the following informalities: The claims utilize several acronyms “MHC and pMHC” without first defining what it represents in the independent claim. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym. For example, MHC is major histocompatibility complex. However, Applicant is cautioned not to introduce new matter into the claims. Appropriate correction is required.
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.
12. Claims 32 and 33 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 pre-AIA the applicant regards as the invention.
A. Claim 32 step iii is vague and indefinite because it is unclear as to what will be immobilized on the array. As recited the claim requires either “at least one molecule or at least one complex that has bound thereto at least one anti-MHC antibody or at least one anti-pan-Human Leukocyte Antigen (HLA) antibody whereby a pMHC in a sample flowing through said channel can be extracted from said sample using said at least one antibody;”. This wording is ambiguous because the use of the at least one molecule is unclear. Will the molecule also bind pMHC in the sample or is it directed to another different target? In order to obviate this rejection the utility of the at least one molecule should be explained in the claim. Please clarify.
B. Regarding claim 32 step v, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is suggested that the term is omitted in order to obviate the rejection.
Claim Rejections - 35 USC § 103
13. 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.
14. Claims 32 and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al., Lab on a Chip, 20(6), 1072-1082) and Rodriguez-Ruiz et al. ("Protein separation under a microfluidic regime", Analyst, vol. 143, no. 3, 1 January 2018, pages 606-619, IDS filed 11/4/22) in view of Klein et al. (US 2018/0356424) and further in view of Rosato et al. (Nature Communications, Vol.10, No.1, February 2019, pages 1-9, IDS filed 11/4/22).
Li et al. teach microfluidic devices with micropillars arranged in arrays with attached compositions. See page 1074, "To achieve isolation of target immune cells from the [samples, the researchers] developed and fabricated a microfluidic device (Fig. 1a) containing two regions of microstructure arrays with surface modification for capturing target immune cells with a defined surface protein expression. The first region is an array of micropillars for cell focusing while the second stage is an array of micro- sieves for cell capture The device has an inlet and an outlet connecting to the two micro-structured regions."
While, Rodriguez-Ruiz et al. disclose that protein separation/isolation using microfluidic devices is common general knowledge and a trend that is increasing in the art. Table 1 shows that monoliths (micropillars) are a common approach in the microfluidic device field.
Li et al. and Rodriguez-Ruiz et al. differ from the instant invention in not specifically utilizing anti-MHC antibodies to pull down pMHC (MHC peptides) from a sample.
However, compositions involving MHC, anti-MHC antibodies, pMHC binding compositions were taught and routinely employed by the prior art. For example, Klein et al. (US 2018/0356424) teach procedures employing immobilized MHC compositions in an array format. The disclosure provides compositions comprising at least one assembly comprising a peptide and a major histocompatibility complex (MHC), wherein the peptide is an integral component of the MHC, wherein the peptide is attached to a surface at its C-terminus through a linker and wherein the peptide is synthesized on the surface. In certain embodiments, the compositions comprise a plurality of assemblies in a spatially-ordered array. The disclosure provides methods for making and using these compositions. See abstract.
The method comprising contacting a surface comprising at least one peptide and an MHC composition under conditions suitable for generating at least one peptide-MHC assembly[0073]. [0074] Prior to contacting the surface, the MHC composition is produced by a method comprising the steps of: (a) incubating the MHC composition at 4° C. overnight, (b) separating a precipitate from the MHC composition, and (c) collecting the precipitate-free MHC composition for contacting the surface.
[0075] The separating step may further comprise a centrifugation step wherein the precipitate-free MHC composition is a supernatant produced from the centrifugation.
[0078] A composition as disclosed may be used for the identification of one or more peptide antigens that are immunodominant when presented by an MHC in vivo, and, optionally immunogenic. The MHC may be a class I or II MHC, the peptide antigen may be a neoantigen which may comprise one or more amino acid(s) essential for binding the MHC. One or more amino acid(s) of the neoantigen that are not essential for binding the MHC may comprise one or more substitution of the amino acid sequence compared to a wild type sequence of the peptide. The peptide antigen may also be a self-antigen, which may stimulate a T-cell and induces an autoimmune response.
[0123] The peptides of the disclosure may comprise an epitope of an antibody used to detect the peptide or the peptide-MHC complex. Moreover, antibodies may be contacted to the compositions of the disclosure to determine the epitope of the antibody, including, a naturally occurring antibody. The term “epitope” refers to an antigenic determinant of a polypeptide. An epitope could comprise three amino acids in a spatial conformation, which is unique to the epitope.
The researchers taught that [0004] there has been a long-felt but unmet need in the art for a surface-bound peptide presented by properly assembled major histocompatibility complex (MHC) that can be synthesized in situ for in vitro analysis of the peptide in an accurate biological context. [And] the disclosure provides a solution to this long-felt but unmet need.
[0005] The disclosure provides an in vitro system for assaying interactions between a peptide presented by an assembled major histocompatibility complex (MHC) and an immune cell (e.g. a T-cell) to identify those peptides and cells that are biologically relevant in vivo. The compositions of the disclosure provide a unique ability to identify single peptides that are immunodominant in vivo by providing a surface with each peptide attached to the surface in a spatially ordered array. The spatial ordering of the peptides is made possible by synthesizing each peptide in situ on the surface.
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to immobilize MHC complexes as taught by Klein et al. into the microfluidic devices of Li et al. and Rodriguez-Ruiz et al. to [0005] identify single peptides that are immunodominant in vivo by providing a surface with each peptide attached to the surface in a spatially ordered array. The spatial ordering of the peptides is made possible by synthesizing each peptide in situ on the surface. And [0004] there has been a long-felt but unmet need in the art for a surface-bound peptide presented by properly assembled major histocompatibility complex (MHC) that can be synthesized in situ for in vitro analysis of the peptide in an accurate biological context. This disclosure provides a solution to this long-felt but unmet need.
Li et al. and Rodriguez-Ruiz et al. in view of Klein et al. differ from the instant invention in not specifically teaching T cell expansion or activation for patient treatment.
However, Rosato et al. discloses that virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. It is concluded that peptides from common pathogens provide a unique therapeutic avenue for cancer immunotherapy.
Absent evidence to the contrary the use of known peptides as T cell enhancers for cancer therapy is deemed an obvious design choice previously taught by the prior art. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945); In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988).
Therefore it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the identified MHC complexes taught by Li et al. and Rodriguez-Ruiz et al. in view of Klein et al. and select T cells stimulated/activated by the tumor specific antigen (such as MHC) as taught Rosato et al. for treating cancer in order to prevent patient death.
15. For reasons aforementioned, no claims are allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa Cook whose telephone number is 571-272-0816. The examiner works a flexible schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3505. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Remsen
571-272-0816
5/30/26
/LISA V COOK/Primary Examiner, Art Unit 1642
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