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
Status of the Claims
Claims 312-341 are pending and the subject of this NON-FINAL Office Action.
Claim Objection
Claim 318 is objected to because “Wherein” is capitalized; it should start with a lower case “w.”
Claim Rejection - 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.
Claims 312-341 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The metes and bounds of the claims are so unclear and confusing that the Office cannot determine if the instant claims are patentable because it would require the Office to speculate as to the metes and bounds of the instant claims. See MPEP § 2173.06 (“Second, where there is a great deal of confusion and uncertainty as to the proper interpretation of the limitations of a claim, it would not be proper to reject such a claim on the basis of prior art. As stated in In re Steele, 305 F.2d 859, 134 USPQ 292 (CCPA 1962), a rejection under 35 U.S.C. 103 should not be based on considerable speculation about the meaning of terms employed in a claim or assumptions that must be made as to the scope of the claims.”).
At the point of potential novelty and non-obviousness, Applicants resort to a vague, poorly-defined phrase they invented. Specifically, at step (b), “contacting a Barcode Transfer Reagent (BTR) comprising an additional barcode molecule with the terminal amino acid or a terminal amino acid derivative, thereby generating a barcoded-amino acid complex (BTR-AC).” The BTR is never clearly defined. The specification dodges and weaves:
Barcode Transfer Reagents: The BTR may couple or bind to the terminal amino acid of the peptide or protein to generate the BTR-AC. . . .
[ . . . ]
Design of Barcode Transfer Reagent: The reagent which reacts to the termini of peptides for the sequential removal of amino acids may have three components. The BTRs may comprise (1) a barcode containing cycle information. In principle, a variety of molecules can be used as barcodes, such as DNA, RNA, proteins, synthetic molecules, or other materials. The second possible component is (2) a primer that hybridizes to a site on the peptide barcode (this is specific to DNA/RNA). The last component is a (3) chemical moiety that becomes conjugated to either the N-, C-, or both terminal ends of a peptide.
[ . . . ]
Step 4: Barcode Transfer Reagent (BTR) Attachment
The Barcode Transfer Reagent (BTR) reacts to the termini or internally to peptides and proteins for the sequential removal of amino acids. This reagent may contain at least three components. One possible component is a DNA sequence containing cycle information. In principle, a variety of molecules can be used as barcodes, such as DNA, RNA, HNA, CeNA, proteins, synthetic molecules, or other materials. The second possible component is a primer that hybridizes to a site on the peptide barcode (this is specific to DNA/RNA/HNA/CeNA). Another component is a chemical moiety that conjugates to either the N-, C-, or both terminal ends of a peptide.
[ . . . ]
Example 5a. Preparing Barcode Transfer Reagent (Btr)
General Principle: The Barcode Transfer Reagent (BTR) possesses two functionalities. The first is a moiety capable of sequentially removing amino acids from the termini of peptides. This moiety can be ClickP, (as described in U.S. Pat. No. 11,499,979), PITC, dinitrofluorobenzene, dansyl chloride, or other variants. The second component is a DNA sequence onto which a copy of the peptide barcode will be transferred once the BTR reacts to a peptide. The DNA sequence, at a minimum, possesses a sequence that denotes the cycle number during sequencing. Primer sequences for DNA amplification may be added as well. Primer sequences to initialize the copying of the parent peptide barcode may also be included.
(paras. 0156, 0279, 0362 & 0448; emphases added). As is clear from the descriptions above, the BTR may be many different things; but its is never clearly and minimally defined. For example, it is not clear from this description if it must be a nucleic acid, much less any particular type (e.g. DNA); or whether it can be a peptide, or other material. Moreover, one description states the BTR reacts to the terminus of a peptide; another states it can react to an internal amino acid of the peptide; yet another states it couples or binds to the terminal amino acid of the peptide or protein; and another states it possesses two functionalities of sequentially removing amino acids from the termini of peptides, and DNA sequence onto which a copy of the peptide barcode will be transferred once the BTR reacts to a peptide. In other words, Applicants cannot seem to make up their mind as to the minimal structural requirements of the BTR. This “BTR” is never used in the prior art; Applicants have invented the phrase; yet, they fail to clearly define it. Thus, it is unclear what is the BTR, much less its minimal structure.
Although the claims state the BTR includes “an additional barcode molecule,” yet even this is never clearly defined. For example, the specification never states whether this is a nucleic acid, protein, carbohydrate or some other molecule; much less which specific type. The specification simply never addresses what is “an additional barcode molecule.” At best, the specification describes a “barcode” as “generally refers to an identifying feature that may be used to distinguish similar items” (para. 0115; emphasis added). In other words, it could be some vague “identifying feature” (whatever this means); or not (“generally”). Applicants have simply failed to clearly define this critical feature such that the Examiner can apply prior art without conjecture as to it’s meaning, and metes and bounds.
Prior Art
The following prior art teaches peptide sequencing using peptides with N- and C-terminal barcode oligos that are used to hybridize to each other and generate extension products that are later cleaved from the peptide and sequenced: US20190145982.
Allowable Subject Matter
Based on a review of the examples in the specification, the following subject matter is allowable:
312. A method for processing a peptide, comprising:
(a) providing the peptide comprising an N-terminal amino acid, wherein the peptide is coupled to a barcode molecule on the C-terminal amino acid;
(b) contacting a Barcode Transfer Reagent (BTR) comprising an additional barcode molecule and a primer with the N-terminal amino acid
(c) hybridizing the additional barcode molecule of the BTR to the barcode molecule that is coupled to the peptide, and extending the BTR; and
(d) cleaving the N-terminal amino acid
(e) contacting the cleaved N-terminal amino acid with a binding agent.
The closest prior art (e.g. US20190145982) teaches N- and C-terminal barcodes that are used to hybridize to each other and extend in order to create barcoded oligos to sequence peptides. The difference here is that none of this prior art teaches an amino acid left on the N-terminus for binding agent attachment (e.g. for enrichment). Instead, the prior art teaches enrichment via baits (US20190145982, Fig. 17); thus, they do not provide a reason or motivation to leave the N-terminus aa.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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/AARON A PRIEST/Primary Examiner, Art Unit 1681
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