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 .
Priority
The instant application (filed on 07/25/2024) is a 371 national stage application of PCT/IB2023/050713 (filed on 01/27/2023) with a claim to foreign priority to application IT102022000001400 (filed 01/27/2022). In the interests of customer service and compact prosecution it is noted that a translation of the foreign application (IT102022000001400) has not been made of record in accordance with 37 CFR 1.55, and so Applicant cannot rely upon the certified copy of the foreign priority application to overcome any rejection. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies (identified as I. and II. below) and the required response to this Office Action are as follows:
I. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). The sequence disclosures located on page 6 of the specification as filed (disclosure of polynucleotide sequences used as primers) are not accompanied by any SEQ ID NO: from the sequence listing.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
II. Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on page 6 of the specification as filed (disclosure of polynucleotide sequences used as primers) are not included in the Sequence Listing.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Objections
Claim 1, 3 and 4 is objected to because of the following informalities:
Claim 1 includes parenthetical numbers (i.e.: (30) and (20) ) related to elements of the Figure 2 of the drawings, but the reference to the elements by number is unnecessary in the claim.
Claim 1 recites the terms “Cycle threshold” and the associated abbreviation “Ct”, but the capitalization of the “C” in the phrase “Cycle threshold” is unnecessary. Additionally the abbreviation “Ct” does not need to be in parentheses in subsequent instances of the abbreviation in the claims.
Claims 3 and 4 recite phage clone identifiers as parenthetical terms, but where the identifiers are associated with the particularly recited phage clones, the parentheses are unnecessary. For example, where claim 3 recites “phage clones (12CIII1) expressing peptide”, the phrase “phage clones 12CIII1 expressing peptide” is appropriate.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Indefiniteness
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 1-7 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 1-7 are unclear over the stated purpose of the methods as “for diagnosing Alzheimer’s disease”, as recited in the preamble of claim 1, in light of the required practical steps of the claims. There is no step in which Alzheimer’s disease (AD) is diagnosed in any individual. Claim 1 recites a final “wherein” clause which states ct and Wbp ranges that are asserted to be indicative of an individual having, or not having AD, but such a recitation is not a requirement that any such ct or Wbp is in fact present and detected. In the insntat case the ranges include a conclusion that the individual does not suffer from AD, and so it is unclear how that embodiment is “diagnosing Alzheimer’s disease”. Additionally it is noted that the recited ranges do not include they entire ranges of possible results for ct and Wbp, and have gaps, where the specification at page 10 indicates such results are an “uncertain test”. It is unclear how any “uncertain tes” as encompassed by the claims, is “diagnosing Alzheimer’s disease”.
Claims 1-7 are unclear over rection of the limitation “detecting, by real-time polymerase chain reaction (PCR), the quantity of phage clones (30) of said preparation to which said antibodies (20) have bound, by determining Cycle threshold (Ct) obtained by said real-time PCR”, in light of the recited “wherein a (Ct) 16 … indicates that the individual does not suffer from Alzheimer's disease and a (Ct) 14 … indicates that the individual suffers from Alzheimer's disease”, as recited in claim 1. The limitations are unclear because while they appear to require a particular cycle number for achieving a threshold, there is no indication as to what that threshold is. For example, the requirements of the claim are different if the threshold is a detection of an amount that is a signal indicative of 0.1 ug/ml, versus the threshold being an amount that is a signal indicative of 0.01 ug/ml. As used in the related art, a cycle threshold (Ct value) is the number of replication cycles required for a PCR signal to cross a set background threshold. It measures how much target genetic material is in a sample. A lower Ct value means more starting material and a higher amount of virus or target gene. But the Ct is dependent upon what value is considered the set background threshold, which is not defined in the claims.
Claims 1-7 are unclear over rection of the limitation “measuring bound phage clones weight (Wpb)” in light of the recited “wherein … a Wpb < 0.1 ug/mL indicates that the individual does not suffer from Alzheimer's disease and … Wpb > 0.5 ug/mL indicates that the individual suffers from Alzheimer's disease” because the recited elements are not weights. A value labeled as “ug/mL” is a concentration, it is not a weight.
Claim 4 is unclear over recitation of the limitation “preparations of phage clones (12CIII3) expressing peptides of SEQ ID NO: 5 determines the pathological stage of Alzheimer's disease”. The claim is unclear because the other groups of phage clones are recited in the claims as either “determines whether the individual suffers from Alzheimer's disease” or “identifies individuals suffering from Alzheimer's disease as well as the pathological stage of Alzheimer's disease”. It is unclear how the 12CIII3 phage can be used to determine a stage of AD without also determining that AD is present.
Claim 6 is unclear over recitation of the limitation “the phage clones expressing peptides that do not mimic conformational epitopes of the Aβ-42 peptide are 9IV1”, because there is no definition in the claim for what is required by a “9IV1” phage clone.
Claim Rejections - 35 USC § 112 – Written Description
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 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant rejection of claim for encompassing subject matter that was not adequately described in the application as originally filed is relevant to several aspects of the claims.
As a first aspect, the claims are directed to the use of phage clones that express peptides that are mimics of conformational epitopes of Aβ-42 peptide as targets to detect antibodies in serum for the diagnosis of AD. But the phage of the claims 1, 2, 5, 6 and 7 are not defined by any particular structure. The breadth of the structures encompassed by the claims in light of the functional requirement of being indicative of the presence of antibodies associated with AD is relevant in light of the related art which teaches that not all epitopes of Aβ-42 generate an immunological response (e.g.: Axelsen (2011)). While the application as filed describes the use of the particular phage clones encoding SEQ ID NO: 1-6, the application does not provide for any other phage clones as encompassed by the claims. Concerning the rejection as it is applied to claim 6, the claim recites “phage clones expressing peptides that do not mimic conformational epitopes of the Aβ-42 peptide are 9IV1”, but neither the claims nor the specification define what is intended or required by a “9IV1” phage clone.
As a second aspect, the claims are directed to the diagnosis of AD based on some detected levels of phage clones bound to antibodies from serum of an individual. But the required diagnostic detections of “wherein a (Ct) > 16 or a Wpb < 0.1 ug/mL indicates that the individual does not suffer from Alzheimer's disease and a (Ct) < 14 or Wpb > 0.5 ug/mL indicates that the individual suffers from Alzheimer's disease” are not adequately described in the application. As noted earlier in this Office Action, the requirement of a Ct identified by a cycle number (i.e.: the cycle number at which a PCR signal achieves some predetermined threshold) is not an adequate description where the threshold signal/value is itself not provided. Furthermore, the application as filed does not provide a description of the required ‘Wbp’ (i.e.: a bound phage clone weight that is any ‘ug/mL’ because ‘ug/mL’ is a concentration, not a weight.
In light of the above detailed deficiencies in the application as filed in consideration of the requirements of the claims, it is the conclusion that the application as filed does not provide an adequate written description of the claimed methods.
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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and natural phenomena without significantly more.
The claim(s) recite(s) a method of diagnosing AD based on a detected amount of antibodies from serum that are bound to a phage clone expression an epitope. Where the claims are directed to determination of the presence of pathology based on a measure of antibody bound to phage, the claims include an abstract an abstract idea which is a mental process; the correlation of data and information to make a judgment or reach a conclusion which can be performed in the human mind (MPEP 2016.04(a)(2)(III). Additionally, where the claims are directed to the association between the presence of antibodies and the presence of AD pathology, and such antibodies are a natural part of the AD pathology, the claims are directed to ta natural phenomenon (MPEP 2106.04(b)).
This judicial exception is not integrated into a practical application because there are no practical steps performed as a result of any diagnosing. The claims end with an asserted association between Ct or Wbp values and the presence or absence of AD pathology.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite only general steps related to phage display mediated immuno-PCR (PD-IPCR), but such methods were well understood, routine and conventional in the related art. Guo et al (2006) (cited on the IDS of 07/25/2024) teaches general methodology of PD-IPCR. And DePlano et al (2020) (cited on the IDS of 07/25/2024) teaches particular phage clones and their detection in the discrimination of sera of AD from healthy individuals. And Rizzo (2020) (cited on the IDS of 07/25/2024) teaches phage display mediated Immuno PCR for Alzheimer’s diagnosis.
Claim Rejections - 35 USC § 102
In the rejection of claims in view of the prior art it is noted that several aspects of the claims have been previously addressed in this Office Action as unclear under 35 USC 112. The claims are addressed here in so far as the prior art teaches the required elements of the claim in at least some broadest reasonable interpretation of the claims in light of the specification.
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.
Claim(s) 1-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rizzo (2020) (cited on the IDS of 07/25/2024).
Relevant to the required methodological steps of the rejected claims, Rizzo teaches Phage display mediated immuno-PCR for Alzheimer’s diagnosis (e.g.: p. 56-72), including providing a serum sample from an individual (e.g.: p.57 – Human samples); providing preparations of phage clones expressing Aβ-42 peptide epitopes and reacting the serum with the phage clones (e.g.: p.63 - Phage mediated Immuno-PCR); and detecting a quantity of phage bound to antibodies of the serum using real-time PCR and determining a cycle threshold (e.g.: p.63 - Quantitative evaluation of phage DNA and standard curves).
Relevant to claim 2-4, Rizzo teaches (e.g.: p.64; p.44) using phage clones identified as:
12III1 (RWPPHFEWHFDD; SEQ ID NO: 2),
12CIII1 (GGGCIEGPCLEG; SEQ ID NO: 1),
12CIII3 (WVGCHGEWCGVW; SEQ ID NO: 5),
12CIII4 (HRGCIEGPCLDA; SEQ ID NO: 6),
12III15 (WEYDRYRGWHIG; SEQ ID NO: 3), and
12IV14(GGHWEWHADYNL; SEQ ID NO: 4)
in order to define the status and stage of AD (e.g.: Graph 1 on p.64-65; Graph 2 on p.66).
Relevant to claims 5 and 6, Rizzo teaches assays using a clone identified as 9IV1, that did not show significant positivity to all tested sera (e.g.: p.67; p.44-45).
Relevant to claim 7, Rizzo teaches steps of washing to remove unbound phage, and heat treating to lyse antibody-bound phage (e.g.: p.60).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/ Primary Examiner, Art Unit 1683
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