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 . Claims included in the prosecution are claims 1-3, 11-14, 17-19 and 28-31.
Applicants' arguments, filed 07/02/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 1-3, 11-14, 17-19, 28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Brady-Kalnay (US 2015/0352192, Dec. 10, 2015), as evidenced by Molyneaux et al. (Small molecule antagonists of PTPmu identified by artificial intelligence-based computational screening block glioma cell migration and growth, Jul 26, 2023) (hereinafter Molyneaux).
Brady-Kalnay discloses a method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an agent that specifically binds to or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule (CAM) or its receptor that is expressed by a cancer cell or another cell in the cancer cell microenvironment (abstract). The agent can include a polypeptide (¶ [0008]). The term “polypeptide” and “peptide” are used interchangeably (¶ [0029]). The Ig superfamily CAM can be a receptor protein tyrosine phosphatase (RPTP) that is proteolytically cleaved to form the extracellular fragment. For example, the RPTP molecule can be PTPµ (¶ [0006]). The extracellular fragment can include an amino acid sequence of SEQ ID NO: 2, and the agent can specifically bind to an extracellular fragment having an amino acid sequence of SEQ ID NO: 2. The agent can further include a polypeptide having an amino acid sequence of SEQ ID NO: 5 (¶ [0008]). Additional residues may be added at either terminus of a polypeptide for the purpose of providing a “linker” by which the polypeptides can be conveniently linked and/or affixed to other polypeptides, proteins, detectable moieties, labels, solid matrices, or carriers (¶ [0064]). Amino acid residue linkers (i.e., peptide spacer) are usually at least one residue and can be 40 or more residues, more often 1 to 10 residues. Typical amino acid residues used for linking include glycine (¶ [0065]). In some embodiments, the linker can be a flexible peptide linker. A flexible peptide linker can be about 20 or fewer amino acids in length. For example, a peptide linker can contain about 12 or fewer amino acid residues, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. In some cases, a peptide linker comprises both glycine and serine (¶ [0066]). The agent can include a detectable moiety. The agent can be detected in vivo by recognizing the detectable moiety. The detectable moiety can be detected by, for example, at least one of gamma imaging, positron emission tomography (PET) imaging, computer tomography (CT) imaging, magnetic resonance imaging, near infrared imaging, or fluorescent imaging (¶ [0010]). The detectable moiety can include a radiolabel (¶ [0100]). The agent, which specifically binds to or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule (CAM) or its receptor that is expressed by a cancer cell or another cell in the cancer cell microenvironment, can be administered in combination with a chemotherapeutic agent or radiotherapeutic agent (¶ [0116]). In some embodiments, the agent can be conjugated onto a nanoparticle (¶ [0109]). The agent can be conjugated to the surface of the nanoparticle via, for example a PEG spacer (¶ [0110]).
The prior art discloses a therapeutically effective amount of an agent that specifically binds to or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule (CAM) or its receptor that is expressed by a cancer cell or another cell in the cancer cell microenvironment (abstract)., wherein the agent is a peptide (¶ [0008]), and the agent is linked to a detectable moiety (¶ [0064]) by amino acid residue linkers (i.e., peptide spacer) (¶ [0065]) containing about 12 or fewer amino acid residues, wherein the amino acid residues may be both glycine and serine (¶ [0066]). Together these would provide a composition as claimed instantly.
The prior art is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP 2143(I)(A).
In regards to instant claim 1 reciting wherein the spacer at least maintains or preserves binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and improves activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent compared to an agent without the spacer, since Brady-Kalnay discloses substantially the same spacer as claimed by disclosing a flexible peptide linker with about 12 or fewer amino acid residues, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12, wherein the amino acids may be glycine and serine, the amino acid residue linker (i.e., spacer) of Brady-Kalnay necessarily at least maintains or preserves binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and improves activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent like the claimed spacer compared to an agent without the spacer.
In regards to instant claims 11, 28 and 30, the claimed amino acid sequence for the peptide spacer would have been obvious from Brady-Kalnay disclosing in paragraph [0066] a flexible peptide linker containing about 12 or fewer amino acid residues wherein the amino acid residues may be a combination of glycine and serine.
In regards to instant claim 12 reciting further including at least one coupling agent that links the spacer to the targeting peptide and/or the at least one of the detectable moiety, therapeutic agent, of theranostic agent, Brady-Kalnay also discloses wherein a therapeutic agent can be conjugated to a nanoparticle via a PEG spacer. Since Brady-Kalnay discloses the use of different linkers/spacers individually, the use of the individual species in combination would have been obvious since it is prima facie obvious to combine two compositions, each of which is taught by Brady-Kalnay to be useful for the same purpose, in order to form a third composition to be used for the very same purpose; the idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06.
In regards to instant claim 13 reciting PTP type IIb, as discussed above, Brady-Kalnay discloses discloses PTPµ. As evidenced by Molyneaux, PTPµ is a member of the receptor protein tyrosine phosphatase IIb family (abstract). As such Brady-Kalnay discloses PTP type IIb, thus meeting the instant claim.
Response to Arguments
Applicant argues that Brady-Kalnay does not teach that the spacer comprises the amino acid sequence of at least one of (GS)a, (GGS)b, (GGGS)c, or (GGGGS)d and wherein a, b, c, and d are each independently 2, 3, 4, 5, or 6 as in claim 1.
The Examiner does not find Applicant’s to be persuasive. As discussed in the rejection, Brady-Kalnay discloses that in some embodiments, the linker can be a flexible peptide linker. A flexible peptide linker can be about 20 or fewer amino acids in length. For example, a peptide linker can contain about 12 or fewer amino acid residues, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. In some cases, a peptide linker comprises both glycine and serine (¶ [0066]). This teaching teaches the claim limitation. Applicant has not explained how this teaching does not meet the claim limitation. As such, Applicant’s argument is unpersuasive.
Applicant argues that Brady-Kalnay does not teach that the recited spacers could at least maintain or preserve binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and improve activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent compared to an agent without the spacer.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, since Brady-Kalnay discloses substantially the same spacer as claimed by disclosing a flexible peptide linker with about 12 or fewer amino acid residues, e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12, wherein the amino acids may be glycine and serine, the amino acid residue linker (i.e., spacer) of Brady-Kalnay necessarily at least maintains or preserves binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and improves activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent like the claimed spacer compared to an agent without the spacer. Applicant has not addressed this argument. Therefore, the rejection is maintained and Applicant’s argument is unpersuasive.
Applicant argues that the claimed invention exhibits unexpected results. Peptide 2 having the polyglycine spacer had improved average radiant efficiency compared to Peptide 1 without a space in vivo. Peptides 3-4 having glycine/serine spacers had even more improved average radiant efficiency.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has shown wherein having a spacer is more advantageous than not having a spacer. However, this does not appear to be unexpected since as discussed in the rejection, Brady-Kalany discloses in paragraph [0066] using a flexible peptide linker with about 12 or fewer amino acids, specifically 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. The instant specification discloses in paragraph [00095] wherein the peptide spacer may be flexible and have 3-12 amino acids. Thus, the flexible peptide linker is a peptide spacer. As such, since using a peptide spacer is known in the art, Applicant's finding of using a peptide spacer is advantageous does not appear to be unexpected. Applicant has not shown wherein using specific spacer of the claims is advantageous to show that the claimed invention is unexpected. As such, Applicant’s argument is unpersuasive.
Applicant argues that Applicant argues that there is no indication that a flexible peptide would be expected to result in increased binding affinity of a targeting peptide and/or activity of a linked detectable moiety.
The Examiner does not find Applicant’s argument to be persuasive. The instant specification discloses in paragraph [00093] wherein the spacer includes at least three natural or non-natural amino acids and have a structure effective to at least maintain or preserve binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent. Typical amino acid residues used for use in the spacer are glycine, serine, tyrosine, cysteine, lysine, glutamic and aspartic acid, or the like. The flexible peptide linker (i.e., spacer) of Brady-Kalany contains 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 amino acids, wherein the amino acids comprise two or more of glycine, serine, alanine, and threonine. Therefore, since having at least three amino acids, wherein the amino acids may be glycine and/or serine maintains or preserves binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent, and Brady-Kalany discloses substantially the same spacer, one of ordinary skill in the art would reasonably expect the flexible peptide linker (i.e., spacer) of Brady-Kalany to maintain and preserve binding affinity of the linked targeting peptide to the proteolytically cleaved extracellular fragment and activity of the at least one of the linked detectable moiety, therapeutic agent, or a theranostic agent like the claimed spacer. Once a reference teaching appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. See MPEP 2112(V). Applicant has not shown wherein achieving the claimed property is specific to the claimed spacer with a specific amino acid sequence. As such, Applicant’s argument is unpersuasive.
Allowable Subject Matter
Claims 29 and 31 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The closest prior art appears to be Brady-Kalnay. Brady-Kalnay does not disclose wherein the peptide linker may comprise the amino acids: phenylalanine, tryptophane, and/or proline and there does not appear to be motivation to modify the peptide linker of Brady-Kalnay to incorporate these amino acids with a reasonable expectation of success.
Conclusion
Claims 1-3, 11-14, 17-19, 28 and 30 are rejected.
Claims 29 and 31 are objected to.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRACY LIU whose telephone number is (571)270-5115. The examiner can normally be reached Mon-Fri 9 am - 5 pm.
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/TRACY LIU/Primary Examiner, Art Unit 1614
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