DETAILED ACTION
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 .
Applicant’s election without traverse of Group I, claims 1, 2, 10, 15, 19, 23, 27, 35, 40, 41, 47, 52, 57, 58, 63, 70, 81, 85 in the reply filed on 11/25/2025 is acknowledged. Note, kit claim 106 should have grouped to invention III (see previous restriction office action). Examiner inadvertently grouped kit claim 106 in Group I. Thus, group I should not include claim 106.
Applicants also elected species of SEQ ID No. 2179 for prosecution.
Claims 1, 2, 10, 15, 19, 23, 27, 35, 40, 41, 47, 52, 57, 58, 63, 70, 81, 85, 95-96 and 106 are pending, and claims 95-96 and 106 are withdrawn from further consideration.
Currently, claims 1, 2, 10, 15, 19, 23, 27, 35, 40, 41, 47, 52, 57, 58, 63, 70, 81, and 85 are under examination.
Specification
The disclosure is objected to because of the following informalities: Experiments #4 the brief description of GVAPGIGPGG and experiment #5 i) a sequence of GVAPGIGPGG (SEQ ID NO: ) (ii) a sequence of VAAAAKSAAK (SEQ ID NO: ) (iii) a sequence of GPGGVAAA (SEQ ID NO: ). The above disclosed portions of sequences that do not appear to be identified with a SEQ ID number. Applicant is reminded that if the disclosed nucleotide encompasses more than 10 nucleotides, or the disclosed polypeptide encompasses more than 4 amino acid residues, then applicant must comply with the Sequence Rules as set forth in 37 CFR 1.821-1.825. Appropriate correction is required.
Claim Objections
Claims 2 and 52 are objected to because of the following informalities:
Claim 2, part b, line 3, the word “amno” is misspelled.
Claim 52, part (a), line 7, the word “protion” is misspelled.
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.
Claims 1, 2, 10, 15, 19, 23, 27, 35, 41, 47, 52, 57, 58, 63, 70, 81, and 85 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.
As to claims 1, 2, 41,47, 52, 57-58, 63, MPEP 2173.05(s)“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or Table is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).” It is suggested using SEQ ID Nos for the claim language.
As to claim 2, step b, the polypeptide portion “comprises at least four, at least five, at least six….ten consecutive amino acid residues.” is not clear. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “at least four”, and the claim also recites “at least five...., at least ten consecutive amino acid residues….”, which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Similarly step (e ), (f) and (g) shares the same problem.
As to claim 10, step a, the term “nominal” for threshold is not defined in the specification. Therefore it is not clear what amount of peptide meets the limit of “nominal” threshold. See MPEP 2173.05(d).
As to claim 15, step a, “said mammalian protease is preferentially expressed..”. The term “preferentially” is similar to “preferable or preferably” which lacks meets and bounds, i.e. is it or not expressed as claimed. See MPEP 2173.05(d)
As to claim 23, step c , line 2 and last 12th line, the phrase "for example, and not limited to" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
As to claim 23, step c, line 13, “such as” lacks meets and bounds. See MPEP 2173.05(d).
As to claim 27, it is not clear whether the therapeutic agent contain all components of a, b, and c? Or components a, b and c are Markush selection. Please clarify. Similarly claim 85 shares the same problem.
As to claim 41, step (d)(ii), last two lines, the phrase “contains at least five, at least six….ten consecutive amino acid residues” shares the same problem as above in terms of the definite range and limitation. MPEP 2173.05(d).
As to claim 52, step (b), the phrase the polypeptide substrate…has at most three amino acid substitutions, at most two amino acid substitutions, or at most one amino acid substitution..” shares the same issue as above in terms of definite range and limitation. Similarly claim 63, step (a)(i), (b) and (d) also share the same problem.
As to claim 58, step (a)-(c ), “at least seven, at least eight, at least nine…ten” also shares the same problem with respect to definite limitation and range as above.
claim 58, step f, the term “nominal” threshold, it is not clear what amount of peptide meets the limit of “nominal” threshold.
As to claim 70, step b, line 1, “preferentially expressed” lacks meets and bounds.
As to claim 81, step (a ), the phrase "for example, and not limited to" as well as “such as” render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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, 2, 10, 15, 19, 23, 27, and 35 are rejected under 35 U.S.C. 101 the claimed invention is directed to law of nature without significantly more. The invention directs to a method for assessing a likelihood of a subject being responsive to a therapeutic agent that is activatable by a mammalian protease expressed in the subject having a disease or disorder. The claimed method comprises determining in a biological sample from the subject a presence or amount of a proteolytic peptide product produced by the mammalian protease as shown in Column V, IV or VI of Table A, wherein the subject would be likely to respond to said therapeutic agent if the peptide is present or amounts exceeds a threshold. The law of nature refers to (1) measuring a proteolytic peptide as from Table A column IV, V or VI produced by action of a protease in a subject, and (2) correlating the presence or exceeding a threshold value of the peptide to a likelihood of the subject being responsive to a therapeutic that is activable by the same protease expressed in said subject. Therefore, the claims encompass the judicial exception of a natural correlation.
This judicial exception is not integrated into a practical application because no extra step of specific treatment is incorporated in the claim. See MPEP 2106.04(d)(2)
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because all the sample obtaining, processing and measuring specific natural molecules are common, routine, and well-known in the field, such as LC-MS, MALDI-TOF, ELISA (See Examples 3-5). These steps are recited at a high level of generality, and are necessary data gathering steps that feed into the determining step. One cannot do the determining step without getting the data. This weighs against it being significantly more.
Claim 40 is allowed. The following is an examiner’s statement of reasons for allowance: Prior teaches using proteolytic biomarker peptides for diagnosis of protease-associated diseases, such as cancer and connective tissue disease (arthritis) (WO2013182237; IDS reference). The novelty of the current method is the use of a proteolytic peptide biomarker cleaved by a protease in a subject as an indicator that a subject is likely to respond to an activable therapeutic agent (prodrug) comprising a peptide substrate cleavable by the same protease in the subject and thus more active ingredient can be released from the therapeutic agent when administering the therapeutic agent to the subject. The peptide biomarker comprises a portion identical to at least four consecutive amino acid residues of said activable therapeutic peptide substrate sequence that is either N-terminal or C-terminal of a scissile bond cleavable by said protease. The closest prior art is the reference of Choi (Theranostic 2012 2:156; IDS reference) where Choi reviews peptide-linked prodrug and its function via specific enzymatic cleavage in releasing the active ingredient (see page 157, left column, last paragraph to first paragraph right column; also see Table 2 list of substrates vs. specific cleavage enzymes). However no disclosure from Choi teaches or suggests of instant method for assessing a likelihood of a subject being responsive to a peptide-linked therapeutic that is activable by a protease and the protease-cleaved peptide can be an indicator of likelihood of responsiveness to said therapeutic.
Comments: as to claims 1, and 57, the elected proteolytic peptide SEQ ID No 2179 and SEQ ID No. 1989-1999 are free of prior art but subject to 35 USC 101 and 35 USC 112(b) rejection. Hancock (US 20090035797) also teaches measuring SEQ ID No. 2179 (RPPGFSPF) in normal healthy subjects (See SEQ ID No. 2 in Table 3). However Hancock dos not teach using SEQ ID No. 2179 for assessing the likelihood of a subject being responsive to a therapeutic agent activable by a protease capable of producing the proteolytic SED ID 2179. It is noted that the total number SEQ ID Nos in column VI, V and VI in Table A exceeds 900. Therefore in response to this Office Action, please elect 10 more SEQ ID Nos in total from column VI, V and VI in Table A for prosecution. Should the SEQ ID Nos be found free of prior art, more SEQ ID Nos would be continued searched.
Conclusion
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CHANGHWA J. CHEU
Primary Examiner
Art Unit 1678
/CHANGHWA J CHEU/Primary Examiner, Art Unit 1678
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