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 Claims
Examined Herein: 1-16
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PCT/KR2021/010704 on 8/12/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/14/2023 and 12/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 2/14/2023 are accepted.
Withdrawn Rejections
The rejection of claims 1-16 under 35 U.S.C. 102(a)(1) over Kim is hereby withdrawn in view of Applicant’s claim of priority to application PCT/KR2021/010704, thereby disqualifying Kim as prior art.
The rejection of claims 1-4 on the ground of nonstatutory double patenting (NSDP) over claim 1 of U.S. Patent No. 11,618,916 B2 in view of Jiang and Kim, is hereby withdrawn in view of Applicant’s claim of priority to application PCT/KR2021/010704, thereby disqualifying Kim as prior art and the basis for which the rejection relied upon.
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 1-6 and 8-16 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.
Claim 12 recites the limitation "the subject." There is insufficient antecedent basis for this limitation in the claim. Dependent claims fall therewith.
Claim 14, which is dependent upon claim 12, recites the limitation “and the EGF.” However, it is unclear which EGF the claim refers to the EGF present the complex or the EGF present in the prodrug complex. Appropriate clarification or correction is required.
Claim 9 recites the limitation "the fluorescence intensity is detected." There is insufficient antecedent basis for this limitation in the claim. Claim 8, from which claim 9 depends, does not describe a detection step. It is unclear whether “detected” refers to the measured fluorescence intensity recited in the claim 8. Appropriate clarification or correction is required.
Claim 11 recites the limitation "the fluorescence intensity is detected." There is insufficient antecedent basis for this limitation in the claim. Claim 10, from which claim 11 depends, does not describe a detection step. Appropriate clarification or correction is required.
With respect to claim 1, 8, and 10, the term “predicting medicinal efficacy” renders the claim indefinite. The term is not ordinarily understood by one reasonably skilled in the art, nor is the term
defined by the claim or the specification. Accordingly, one of ordinary skill in the art would not be reasonably apprised of the scope of the claims. Dependent claims fall therewith.
Claim 8 recites the limitation “A method… comprising a step of treating… a sample… with the composition for diagnosing colon cancer or predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity.” As written, this limitation may be reasonably interpreted in a few ways: (1) a method comprising a step of treating a sample with the composition according to claim 1 and measuring fluorescence intensity; (2) a method comprising a step of treating a sample with the composition for diagnosing colon cancer, or alternatively, predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity; and (3) a method comprising a step of treating a sample with the composition for diagnosing colon cancer and measuring fluorescence intensity, or alternatively, predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity. With respect to the interpretation “a method comprising a step of predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity,” there is insufficient antecedent basis for this limitation in the claim, as claim 1 is drawn to a composition. With respect to interpretations (2) and (3), it is unclear what the target of the fluorescence intensity measurement is and how the measurement relates to predicting medicinal efficacy. Accordingly, the metes and bounds of the claim cannot be reasonably determined, rendering the claim indefinite. Appropriate correction is required. Dependent claims fall therewith.
Claim 10 recites the limitation “A method… comprising a step of treating… a sample isolated from a cancer patient who is taking the anticancer drug with the composition for diagnosing colon cancer or predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity.” As written, this limitation may be reasonably interpreted in a few ways: (1) a method comprising a step of treating a sample isolated from a cancer patient (who is taking the anticancer drug), with the composition according to claim 1 and measuring fluorescence intensity; (2) a method comprising a step of treating a sample isolated from a cancer patient (who is taking both the anticancer drug and the composition according to claim 1), and measuring fluorescence intensity; (3) a method comprising a step of treating a sample isolated from a cancer patient (who is taking the anticancer drug with the composition for diagnosing colon cancer), or alternatively, predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity; (4) a method comprising a step of treating a sample isolated from a cancer patient (who is taking both the anticancer drug and the composition for diagnosing colon cancer), or alternatively, predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity. With respect to the interpretation “a method comprising a step of predicting medicinal efficacy according to claim 1 and measuring fluorescence intensity,” there is insufficient antecedent basis for this limitation in the claim, as claim 1 is drawn to a composition. With respect to interpretations (3) and (4), it is unclear what the target of the fluorescence intensity measurement is and how the measurement relates to predicting medicinal efficacy. Accordingly, the metes and bounds of the claim cannot be reasonably determined, rendering the claim indefinite. Appropriate correction is required. Dependent claims fall therewith.
Claim Rejections - 35 USC § 103
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.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Rajopadhye (US 2017/0119908 A1, Published 5/4/2017), in view of Nguyen (US 2020/0239522 A1, Published 7/30/2020) and Mayers (US 2006/0018908 A1, Published 1/26/2006).
With respect to claim 1, Rajopadhye discloses the following imaging agent of Formula III:
Fluorophore – [Gly-Phe-Leu-Gly-Gly-Lys] – Quencher – Biological Modifier
comprising a fluorophore and a quencher conjugated on both sides of the peptide, which is cleaved by a lysosomal enzyme present in a tumor cell, and a biological modifier bound to the C-terminal of the peptide. [Rajopadhye, 0132-0144, 0265; See embodiment of Formula III, wherein F = Fluorophore or quencher; L = a bond; ECO = enzymatically cleavable oligopeptide; M = a biological modifier, g is 2, p is 1, and n is 0]
Rajopadhye discloses the biological modifier may be a growth factor or a molecule that targets/inhibits EGFR. [Rajopadhye, 0235, 0238]
The limitation “for diagnosing colon cancer or predicting medicinal efficacy” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 2, Rajopadhye discloses the fluorophore is bound to the N-terminal of the peptide, and the quencher is bound to the epsilon-amino group of a lysine residue of the peptide. [Rajopadhye, 0143, 0144]
With respect to claim 3, Rajopadhye discloses the fluorophore is Cy5, Cy5.5, or Cy7. [Rajopadhye, 0162]
With respect to claim 4, Rajopadhye discloses the quencher is BHQ1, BHQ2, BHQ3, and DABCYL. [Rajopadhye, 0202]
With respect to claim 5, the limitation “wherein the colon cancer [for diagnosing colon cancer] is epidermal growth factor receptor (EGFR)-positive colon cancer” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 6, the limitation “wherein the complex penetrates into a colon cancer cell and emits fluorescence as it is cleaved by an enzyme existing in the lysosome of the colon cancer cell and quenching by the fluorophore and the quencher is resolved” recites a non-limiting description that does not limit the claim to a particular structure and is of no significance to claim construction. MPEP 2111.04.
With respect to claim 7, Rajopadhye discloses the following imaging agent of Formula III:
Fluorophore – [Gly-Phe-Leu-Gly-Gly-Lys] – Quencher – Biological Modifier
comprising a fluorophore and a quencher conjugated on both sides of the peptide, which is cleaved by a lysosomal enzyme present in a tumor cell, and a biological modifier bound to the C-terminal of the peptide. [Rajopadhye, 0132-0144, 0265; See embodiment of Formula III, wherein F = Fluorophore or quencher; L = Linker or bond; ECO = enzymatically cleavable oligopeptide; M = a biological modifier, g is 2, p is 1, and n is 0]
Rajopadhye discloses the biological modifier may be a growth factor or a molecule that targets/inhibits EGFR. [Rajopadhye, 0235, 0238]
The limitation “for identifying prognosis for therapeutic effect in a patient with EGFR positive
colon cancer” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 8, Rajopadhye discloses a method comprising a step of treating a sample isolated from a colon cancer patient with the composition and measuring fluorescence intensity. [Rajopadhye, 0074, 0075, 0077, 0300-0304, 0306, 0307]
The limitation “for providing information for predicting response to an epidermal growth
factor receptor (EGFR)-targeting drug” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 9, the limitation “wherein the subject is determined as responding to
the EGFR drug if the fluorescence intensity is detected” recites a non-distinguishing feature. The claim scope is not limited by claim language that does not require steps to be performed or limit a claim to a particular structure. MPEP 2111.04(I).
With respect to claim 10, Rajopadhye discloses a method comprising a step of treating a sample isolated from a colon cancer patient taking an anticancer drug with the composition and measuring fluorescence intensity. [Rajopadhye, 0074, 0075, 0077, 0300-0304, 0306, 0307]
With respect to claim 11, the limitation “wherein it is determined that the anticancer drug has
no therapeutic effect for the colon cancer patient if the fluorescence intensity is detected” recites a non-distinguishing feature. The claim scope is not limited by claim language that does not require steps to be performed or limit a claim to a particular structure. MPEP 2111.04(I).
With respect to claim 12, Rajopadhye discloses a pharmaceutical composition comprising the following imaging agents of Formula III and I, respectively:
Fluorophore – [Gly-Phe-Leu-Gly-Gly-Lys] – Quencher – Biological Modifier
comprising a fluorophore and a quencher conjugated on both sides of the peptide, which is cleaved by a lysosomal enzyme present in a tumor cell, and a biological modifier bound to the C-terminal of the peptide. [Rajopadhye, 0132-0144, 0265, 0277; See embodiment of Formula III, wherein F = Fluorophore or quencher; L = Linker or bond; ECO = enzymatically cleavable oligopeptide; M = a biological modifier, g is 2, p is 1, and n is 0]
Biological Modifier – [Gly-Phe-Leu-Gly-Gly-Lys] – Doxorubicin
comprising a biological modifier and an anticancer drug (doxorubicin) conjugated on both sides of the peptide, which is cleaved by a lysosomal enzyme present in a tumor cell. [Rajopadhye, 0104-0116, 0238, 0265, 0277; See embodiment of Formula I, wherein ECO = enzymatically cleavable oligopeptide; M = a biological modifier, n is 0, each occurrence of m is 1, and each occurrence of f is 0]
Rajopadhye discloses the biological modifier may be a growth factor or a molecule that targets/inhibits EGFR. [Rajopadhye, 0235, 0238]
The limitation “for preventing or treating colon cancer” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 13, the limitation “wherein the colon cancer [for preventing or treating colon cancer] is EGFR-positive colon cancer” recites an intended use and is of no significance to claim construction. MPEP 2111.02.
With respect to claim 14, Rajopadhye discloses the imaging agents may be covalently bonded by a crosslinking agent. [Rajopadhye, 0216]
With respect to claim 15, Rajopadhye discloses the crosslinking agent is N,N′-dicyclohexylcarbodiimide (DCC), SPDP, or sulfo-SMCC. [Rajopadhye, 0217, 0220]
With respect to claim 16, Rajopadhye discloses the anticancer drug is doxorubicin. [Rajopadhye, 0238]
Moreover, Rajopadhye discloses a linker moiety can be used to covalently link one or more fluorophores, quenchers, biological modifiers and non-fluorescent reporters to the enzymatically cleavable oligopeptide, [Rajopadhye, 0216]
Rajopadhye does not disclose the peptide represented by [Gly-Phe-Leu-Gly-Gly-Lys-Gly-Gly] (SEQ ID NO: 1) or that EGF is bound to the C-terminal of the peptide.
However, with respect to claim 1-16, Nguyen discloses several fluorescently-labeled targeting peptides that further comprise a drug, fluorescent moiety, and/or photosensitizing agent bound to the C-terminus of the peptide. Nguyen discloses, in one embodiment, the drug is a growth factor or an EGFR targeting agent. [Nguyen, 0008, 0044-0047, 0229, 0275, 0284] Moreover, Nguyen discloses a peptide linker, GG, may be added to the C-terminus of a targeting peptide to join the peptide and fluorescent moiety or drug. [Nguyen, 0315] Furthermore, Nguyen discloses hydrophilic amino acids, like glycine, increase the solubility of the peptide when added to the C-terminus. [Nguyen, 0318]
Moreover, with respect to claim 1-16, Mayers discloses EGF is a growth factor that targets the epidermal growth factor receptor (EGFR). [Mayers, 0093]
Modifying the compositions and methods disclosed by Rajopadhye by adding Gly-Gly to the C-terminus of the peptide and selecting EGF as the biological modifier, results in the compositions and methods of claim 1-16, wherein:
the peptide is represented by [Gly-Phe-Leu-Gly-Gly-Lys-Gly-Gly] (SEQ ID NO: 1) and EGF is bound to the C-terminal.
It would be obvious one of ordinary skill in the art to modify the compositions and methods disclosed by Rajopadhye by adding Gly-Gly to the C-terminus of the peptide and have a reasonable expectation of success. Rajopadhye discloses a targeting peptide, wherein a quencher and a biological modifier is bound to the C-terminal thereof. Rajopadhye discloses the biological modifier may be a growth factor or EGFR targeting agent. Moreover, Rajopadhye discloses a peptide linker may be used to covalently link the quencher and/or biological modifier to the peptide. Nguyen discloses a targeting peptide, wherein a fluorescent moiety and/or drug, such as a growth factor or EGFR targeting agent, is bound to the C-terminal thereof via a Gly-Gly peptide linker. Thus, Nguyen establishes that Gly-Gly is a suitable peptide linker that may be added to the C-terminus of a targeting peptide in order to join the peptide and a fluorescent moiety and/or drug. Accordingly, the combined teachings of Rajopadhye and Nguyen suggest that Gly-Gly may be added to the C-terminus of the targeting peptide disclosed by Rajopadhye in order to join the peptide and quencher-biological modifier. Therefore, it is reasonable to expect the compositions and methods disclosed by Rajopadhye may be modified by adding Gly-Gly to the C-terminus of the peptide. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Nguyen discloses hydrophilic amino acids, like glycine, increase the solubility of the peptide when added to the C-terminus. [Nguyen, 0318] Therefore, one would have been motivated by the expectation that adding Gly-Gly to the C-terminus of the peptide disclosed by Rajopadhye would increase the solubility of the peptide.
It would be obvious one of ordinary skill in the art to modify the compositions and methods disclosed by Rajopadhye by selecting EGF as the biological modifier and have a reasonable expectation of success. Rajopadhye discloses a peptide, wherein a biological modifier is bound to the C-terminal. Rajopadhye discloses the biological modifier may be a growth factor or EGFR targeting agent. Mayers discloses EGF is a growth factor that targets the epidermal growth factor receptor (EGFR). Thus, Mayers establishes that EGF is a growth factor and an EGFR targeting agent. Accordingly, the combined teachings of Rajopadhye and Mayers suggest that EGF may function as the biological modifier of the peptide conjugate disclosed by Rajopadhye. Therefore, it is reasonable to select EGF as the biological modifier. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. MPEP 2144.07. In the present case, it is prima facie obvious to select EGF based on its suitability as a growth factor and an EGFR targeting agent, for use as a biological modifier.
Response to Arguments
Applicant’s arguments, filed 5/21/2026, with respect to the rejection of claims 1-16 under 35 USC 102(a)(1) and 1-4 under NSDP have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the references cited above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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