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 .
Response to Amendment
Applicant’s amendment filed on 4/30/2026 is acknowledged.
Claims 1-4 and 10-17 are pending and under consideration for their full scope. Claims 5-9 are cancelled.
The following rejections are necessitated by the amendment filed on 04/30/2026.
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 1-4, 10, and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al (PTO-892 filed on 12/31/2025, Reference V; "Fan") in view of Hossein-Nejad-Ariani et al (PTO-892 filed on 12/31/2025, Reference W; "Hossein").
Fan teaches that doxorubicin a common chemotherapy drug has limited use due to dose-limiting toxicities and side effects such as cardiotoxicity and that a peptide-drug conjugate comprising doxorubicin offers a new approach to delivery doxorubicin while limiting side effects and maximizing drug delivery (Fan; page 1; “Introduction”). Fan teaches the synthesis of a peptide-drug conjugate that comprises EGFR-antagonist GE11 conjugated to doxorubicin via a disulfide bond (GE11-DOX) (Fan; pages 1-2; “Introduction”; Section 2.3 and 3.1; Figure 2A) (GE11 is 84.2% sequence identical to instant SEQ ID NO:5 with amino acid substitutions at positions 9 (G to E) and 10 (N to R); see ABSS sequence alignment of the reference GE11 sequence as shown in Figure 2A with the instant SEQ ID NO:5). Fan additionally teaches GE11-DOX, as a pharmaceutical composition, exhibited specific targeting ability to EGFR overexpressing tumor cells when delivered to SMMC-7721, MCF-7, and EGFR overexpressing MCF-7 cells and could be used to increase the therapeutic index of the broad-spectrum anticancer drug doxorubicin by improving its selectivity to cancer cells (Fan; Abstract; “Discussion”; “Conclusion”; Figures 5 and 7).
However, Fan does not teach the peptide-drug conjugate wherein the peptide comprises SEQ ID NO:5 of instant claim 1; wherein the peptide-drug conjugate comprises the peptide of SEQ ID NO:5 conjugated to doxorubicin of instant claim 12; a pharmaceutical compositions comprising the peptide-drug conjugate of claim 1 of instant claim 13; a method of treating cancer comprising administering to a cancer patient in need thereof the peptide-drug conjugate of claim 1 of instant claim 14; and wherein the cancer is triple negative breast cancer of instant claims 16-17.
Hossein does teach that there is a need to expand treatment options for patients with cancer, specifically TNBC, where it has been difficult to target chemotherapy (i.e., doxorubicin) to TNBC due to the lack of well-defined molecular targets (Hossein; page 1, paragraph 1). To overcome this disadvantage, Hossein teaches the design and screen of 30 EGFR targeting peptides for enhanced specificity and proteolytic stability for clinical application to patients with TNBC with GE11 (reference peptide 1) and 29 analogues of GE11 (Hossein; page 1 paragraphs 2-3; Table 1). Hossein teaches the peptides with highest binding to the TNBC cell line were peptides 22, 23, 26, and 27 and did not show substantial increase in affinity to non-cancerous cells (Hossein; page 3, paragraph 3) (see attached ABSS sequence alignment of peptide 22 to instant SEQ ID NO:5) (Peptide 22 is 93.4% identical to instant SEQ ID NO:5 with amino acid substitution at position 10 (N to R)). Hossein does additionally teach the sequences that share high sequence homology to native EGF bind to the same site on EGFR and that EGF shows that E and R may be preferred residues at positions 9 and 10 (Hossein; page 3, paragraph 5; Figure 4a-d) (It is noted peptide 22 with the amino acid substitution of R in position 10 makes peptide 22 100% sequence identical to instant SEQ ID NO:5; See attached ABSS sequence alignment). Hossein additionally teaches the peptides can serve as superior ligands for the targeted delivery of doxorubicin to treat patients with TNBC and improve doxorubicin’s selectivity and cytotoxicity (Hossein; pages 6-7, paragraphs 1-2).
It would have been prima facie obvious before the effective filing date of the instant application, to have modified the GE11-DOX peptide drug conjugate of Fan with peptide 22 with amino acid substitution R at position 10 of Hossein with reasonable expectation of success. One of ordinary skill in the art would have been motivated to substitute GE11 of Fan with peptide 22 with amino acid substitution R at position 10 of Hossein since Fan teaches there is a need to improve the targeted delivery method of doxorubicin to TNBC cells and limit potential side effects and GE11-DOX peptide drug conjugate serves as a superior alternative to doxorubicin alone. Hossein teaches when compared to GE11 alone, peptide 22 exhibited higher binding to EGFR and higher cellular uptake in TNBC cell lines compared to GE11, and that the amino acid substitution of R in position 10 is a preferred residue since it shares higher sequence homology to native EGF and binds EGFR in the same location (Hossein; page 6, paragraph 1). Therefore, it would have been prima facie obvious to a person of ordinary skill in the art to have modified GE11 peptide of the GE11-DOX peptide drug conjugate of Fan with peptide 22 with amino acid substitution R at position 10 of Hossein to yield predictable results of improving peptide binding to EGFR and increasing cellular uptake of doxorubicin to limit off-target side effects and improve the therapeutic efficacy of doxorubicin in patients with TNBC.
It would have been prima facie obvious before the effective filing date of the instant application to have modified the peptide 22 with amino acid substitution R at position 10 – doxorubicin peptide drug conjugate of Fan and Hossein with a pharmaceutical composition of Fan with reasonable expectation of success. One of ordinary skill in the art would have been motivated to combine the peptide-drug conjugate of Fan and Hossein with the pharmaceutical composition of Fan in order to effectively deliver the peptide-drug conjugate to a patient with TNBC.
From the combined teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
Claims 1 -2 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Fan and Hossein as applied to claims 1-4, 10, and 12-17 above, and further in view of Alas et al (PTO-892 filed on 12/31/2025, Reference U; "Alas").
Fan and Hossein have been discussed above. Fan and Hossein do not teach the peptide drug conjugate of claim 10 wherein the linker comprises a thioester, an amide, a carbamate, an ester, or a carbonate of instant claim 11.
However, Alas does teach a peptide drug conjugate with thioester, an amide, a carbamate, an ester, or a carbonate (Alas; Abstract; Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill, in the art as of the effective filing date, to have modified the peptide 22 with amino acid substitution R at position 10 – doxorubicin peptide drug conjugate of Fan and Hossein with the linkers of Alas with reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification as the linker constitutes a feature of the peptide-drug conjugate that can be substituted with another type of linker to perform the same function as the original one. This substitution represents a known and predictable design choice yielding predictable results.
From the combined teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments directed towards the 35 U.S.C. § 103 rejections on pages 7-9 of Applicant’s remarks filed 4/30/2026 have been fully considered but they are not persuasive.
Regarding claims 7-9, 12 and 14-17, the Applicant argues, “In order to make a proper prima facie case of obviousness, the Patent Office must demonstrate: (1) that all elements of a rejected claim are taught or suggested in the prior art; (2) that there is an apparent reason to combine the prior art elements in the manner claimed; and, (3) that the result is predictable. In making this determination, the Patent Office must examine the prior art, design demands, marketplace demands, and the background knowledge of a person of ordinary skill in the art … Regarding SEQ ID NO:5, Hossein does not disclose let alone teach or suggest "[a] peptide-drug conjugate, wherein the peptide comprises SEQ ID NO:5'' as presently claimed. As noted by the Examiner, Hossein states that "[i]t is anticipated that these peptide binds to the same site on EGFR as the native ligand EGF, and comparison of the amino acid sequence of these peptides and EGF shows that E and R may be preferred residues at positions 9 and 10." However, Hossein does not disclose let alone teach or suggest the claimed SEQ ID NO: 5. The identification of the claimed SEQ ID NO: 5 was not predictable a priori, as there are no established rules that allow reliable prediction of peptide sequences with selective binding to triple-negative breast cancer (TNBC) cells. While peptide ligands, once identified, can be used for cargo delivery (e.g., drugs or imaging agents), the specific sequences and their selective binding properties can only be determined through empirical screening and are not obvious from prior art. The claimed peptide-drug conjugate incorporating SEQ ID NO:5 demonstrates a therapeutically meaningful advantage in that it exhibits selective cytotoxicity toward TNBC cells while showing no detectable toxicity toward normal breast cells. This level of tumor-selective activity and reduced off-target toxicity is significant for breast cancer therapy, particularly TNBC, where targeted treatment options are limited. The observed selectivity indicates preferential targeting and functional delivery of the cytotoxic payload to cancer cells, which goes beyond general peptide-drug conjugate concepts described in the prior art, where such level of cell-type selectivity is not necessarily achieved or demonstrated. As such, Hossein also cannot teach or suggest all the limitations of claim 1 and therefore cannot render claim 1 prima facie obvious. In light of the above, neither Fan nor Hossein alone or in combination teach or suggest all the limitations of claim 1 and therefore cannot render claim 1 prima facie obvious. Claims 12 and 14-17 depend from claim 1, directly or indirectly, and include all its limitations, and therefore are also not prima facie obvious over Fan in view of Hossein for the same reasons claim 1 is not prima facie obvious. Thus, Applicant respectfully requests that the rejection against claims 12 and 14-17 be withdrawn. Claims 7-9 are cancelled herein and therefore the rejection against them is now moot.”
Since claims 7-9 are cancelled, the rejection against them is moot.
The Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). It is the Examiner’s position that Hossein does teach, suggest, and provide motivation "[a] peptide-drug conjugate, wherein the peptide comprises SEQ ID NO:5'' as presently claimed (see Figure 4b; page 3, section: In vitro Cell Uptake of Soluble (Free) Peptides; See attached ABSS sequence alignment). In this case, Hossein does teach that E and R are preferred residues at positions 9 and 10 for peptide 22 since the uptake of peptides 26 and 27 was slightly less compared to peptide 22 (substitution of amino acid K for Q9 or N10 compared to peptide 22) and are conserved residues on native EGF (Hossein; see Figure 4b). Peptide 22 with E and R are positions 9 and 10 is 100% sequence identical to instant SEQ ID NO:5 making instant SEQ ID NO:5 predictable a priori.
Additionally, it is the Examiner’s position that Hossein does not merely teach general peptide-drug conjugate concepts as Hossein teaches the intentional alteration of specific amino acids in GE11 to examine which amino acid substitutions resulted significant changes in peptide-EGFR binding and cellular uptake and identify high binding peptides to TNBC cells (Hossein; see pages 2-3, Peptide Array Synthesis, Peptide Library, and Peptide Library Screening Sections). Hossein even notes that “these results suggest that substitution of Q9 with a negatively charged glutamic acid (E) leads to highest cancer cell binding” and that comparison of the amino acid sequence of these peptides and EGF shows that E and R may be preferred residues at positions 9 and 10 (vide infra)” (Hossein; page 3, paragraphs 3 and 5). These peptides (i.e. peptides 22, 23, 26, and 27) exhibited the highest binding to TNBC cell lines from the library screen, did not show any substantial increase in affinity to non-cancerous cells, and exhibited high TNBC cellular uptake (Hossein; page 3, paragraphs 3-6). Therefore, it would be expected for instant SEQ ID NO:5 to also exhibit the same or similar tumor-selective activity and reduced off-target toxicity to the reference peptides 22, 23, 26, and 27 since instant SEQ ID NO:5 is 93.4% sequence identical to reference peptide 22 and contains a preferred Q10R substitution (see attached ABSS sequence alignment). Therefore, applicant’s arguments are not persuasive and the rejection of claims 12 and 14-17 as obvious over Fan in view of Hossein is maintained.
Regarding claim 11, Applicant argues, “The Examiner further cites Alas for its "teach[ing] [of] a peptide drug conjugate with thioester, an amide, a carbamate, and ester, or a carbonate (Alas; Abstract; Figure 1)." However, Alas fails to disclose let alone teach or suggest "[a] peptide-drug conjugate, wherein the peptide comprises SEQ ID NO:5'' as presently claimed. As such, Alas also cannot teach or suggest all the limitations of claim 1 and therefore cannot render claim 1 prima facie obvious. In light of the above, neither Fan, Hossein, nor Alas alone or in combination teach or suggest all the limitations of claim 1 and therefore cannot render claim 1 prima facie obvious. Claim 11 indirectly depends from claim 1, and includes all its limitations, and therefore is also not prima facie obvious over Fan and Hossein as applied to claims 7-9, 12, and 14-17 above, and further in view of Alas for the same reasons claim 1 is not prima facie obvious. Thus, Applicant respectfully requests that the rejection against claim 11 be withdrawn.”
It is the Examiner’s position that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). All of the limitations of the claims are disclosed either in Fan (i.e. peptide-drug conjugate (GE11-DOX conjugated via a disulfide bond used to treat cancer), Hossein (the peptide comprising instant SEQ ID NO:5), or Alas (conjugation methods), and the combination of the references renders the claimed invention obvious. Therefore, applicant’s arguments are not persuasive and the rejection of claim 11 as obvious over Fan and Hossein in view of Alas is maintained.
Conclusion
No claim is 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 LEAH ELIZABETH STEIN whose telephone number is (571)272-0093. The examiner can normally be reached M-F 8-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEAH ELIZABETH STEIN/Examiner, Art Unit 1641
/NORA M ROONEY/Primary Examiner, Art Unit 1641
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