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 Election/Restriction filed on February 03, 2026 is acknowledged.
Claims 50-69 are pending in this application.
Restriction
Applicant’s election of the following species:
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in the reply filed on February 3, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Applicant indicates claims 50-54, 58-60 and 62-69 read on the elected species. A search was conducted on the elected species, and prior art was found. Claim 57 belongs to the species in Group D. Claim 58 does not read on the elected species. Thus, claims 55-56, 58 and 61 are withdrawn from further consideration as being drawn to nonelected species. Claims 50-54, 57, 59-60 and 62-69 are examined on the merits in this office action.
Non-Compliant Amendment
Claim amendment filed on February 3, 2026 is non-compliant. In the claim amendment filed on August 19, 2024, where the Restriction requirement was based off of, claim 50 had been amended as follows:
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. Additionally, new claim 68 had been added and recited:
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.
However, in the claim amendment filed on February 3, 2026, claim 50 recites:
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; and claim 68 recites:
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. For example, claim 50 is missing the sequence identifier and claim 68 is a completely different claim. Applicant is required to correct this in response to this office action.
Objections
The drawings are objected to because of the following minor informalities: Figures 1A and 1B are missing the Y-axes labels. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Claim 50 is objected to for the following minor informality: claim 50 contains the acronym “AMT”, and an acronym in the first instance of claims should be expanded upon/spelled out with the acronym indicated in parentheses, i.e., activated macrophage targeting (AMT). The abbreviations can be used thereafter.
Claim 50 recites, “…wherein the peptide selectively binds to activated macrophages via the AMT amino acid sequences…wherein the composition selectively binds to the activated macrophages.” The recitation is redundant. The peptide is in the composition, and the peptide selectively binds to activated macrophages, thus the composition comprising the peptide would bind to the activated macrophages. Applicant is required to correct this issue.
Claim 67 recites, “…wherein the peptide and the co-composition are not covalently coupled or directly non-covalently associated with each other.” The recitation of “not covalently coupled or directly non-covalently associated with each other” appears to be redundant. Applicant is recommended to amend the claim to recite, “…the peptide and the co-composition are not covalently coupled and/or associated.”
Rejections
35 U.S.C. 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 50-54, 57, 59-60 and 62-69 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.
Claim 50 recites, “A method comprising contacting…wherein the amino acids of X1, X2, and X3 can be any amino acid, and…” The metes and bounds of the claim is unclear since the term “can be” is not an absolute term. The term “can be” implies that X1, X2 and X3 can be any amino acid, including amino acid mimetics. Therefore, it is unclear what amino acids are encompassed within the term “can be”. Because claims 51-54, 57, 59-60 and 62-69 depend from indefinite claim 50 without clarifying the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
Claim 52 recites, “The method of claim 51, wherein the method further comprises, prior to the contacting, administering the composition to the subject.” It is unclear how the contacting would occur in claim 50 if the composition is not first administered to a subject.
35 U.S.C. 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 50-54, 57, 59-60, 62-64 and 68 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ruoslahti grant W81XWH-12-1-0173 (September 2014, pp. 1-8, filed with IDS).
Instant claims are drawn to a method comprising contacting activated macrophages with a composition comprising (i) an isolated peptide comprising an AMT amino acid sequence, wherein the AMT amino acid sequence has the formula X1-R-X2-L-R-S-X3, and the elected species of the AMT peptide sequence is CRVLRSGSC (SEQ ID NO: 1).
Ruoslahti reference teaches instant SEQ ID NO: 1 (CRVLRSGSC (called CRV peptide), p. 9, middle section), and instant SEQ ID NOs: 2, 10, 12, 13, 14 and 17 (see Table 3, peptides 1-2, 4-6 and 9). Ruoslahti reference teaches that CX7C peptide is cyclic (see Figure 1 legend). Ruoslahti reference teaches that the peptide CRV is labeled with green fluorophore (see Figure legends 7-9), meeting the limitation of instant claim 63. Ruoslahti reference teaches delivering compounds to stromal elements and tumor stem cells for therapeutic, imaging and research purposes, and co-administration of a phage library (see for example, p. 1, bottom of introduction paragraph), meeting the limitation of instant claims 50-54, 64 and 68. Ruoslahti reference teaches that peptide motif recognizes tumor macrophages, and that CRV peptide accumulates in tumor macrophages and tumor lymphatics (see p. 14, bullet points 5 and 6) and “CRV recognizes the macrophages and inflammatory sites within tumors” (see bottom of p. 9). Ruoslahti reference teaches that CRV can preferentially homes to the tumors, extravasates outside blood vessels, and co-localizes with markers for macrophages and lymphatic vessels in tumors (Figures 7-11) (see top of p. 10), meeting the limitation of instant claim 62. Ruoslahti reference teaches that CRV does not target a non-malignant site of chronic inflammation (see bottom of p. 12), meeting the limitation of instant claims 50-54. Ruoslahti reference teaches injecting the peptide into atherosclerotic mice with abundant plaque in the aorta (see p. 12, bottom), meeting the limitation of instant claims (see p. 12, bottom), meeting the limitation of instant claims 51-52 and 59. In regards to claims 53-54, 57 and 62, the claims recite an inherent property of the composition/peptide and an end results. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same...[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977)).”
Furthermore, with respect to “wherein the composition has a therapeutic effect (claim 53); wherein the therapeutic effect is one or more (claim 54); wherein the therapeutic effect comprises increase in apoptosis (claim 57); wherein the composition selectively homes to activated macrophages and/or tumor associated macrophages (claim 62); wherein the peptide selectively homes to activated macrophages in vivo, optionally wherein the peptide selectively homes to tumor associated macrophages in vivo (claim 68)” according to MPEP 2111.04: "Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
(C) “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Id. <”. In the instant case, it is not deemed that the “wherein” clause limits the claim to particular structural features.
Since the active method steps, i.e., contacting the isolated peptide of instant SEQ ID NO: 1 with an activated macrophage is the same, the Ruoslahti reference anticipates instant claims 50-54, 57, 59-60, 62-64 and 68.
U.S.C. 103
18. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
19. 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.
20. 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.
21. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
22. Claims 50-54, 57, 59-60, 62-65 and 68 is/are rejected under 35 U.S.C. 103 as being obvious over Ruoslahti grant W81XWH-12-1-0173 (September 2014, pp. 1-8, filed with IDS) in view of Smith et al (US Patent No. 4966848) or Peers et al (US Patent No. 5837218) or Smith et al (US Patent No. 5223421).
The applied reference has a common Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
23. The teachings of Ruoslahti reference is described above.
The difference between the reference and the instant claims is that the reference does not teach modifications of the peptides.
24. However, Smith et al (US Patent ‘848) teach that “An acetyl moiety was discovered as the amino-terminal blocking group of viral coat protein in 1958 and of hormonal peptide in 1959. Since then, a large number of proteins in various organisms have been shown to possess acetylated amino-terminal residues. For example, mouse L-cells and Ehrich ascites cells have about 80% of their intracellular soluble proteins Na-acetylated [and in] lower eukaryotic organisms, about 50%. These data demonstrate that N-acetyl is a very important blocking group. It has been suggested that the biological function of this blocking group may be to protect against premature protein catabolism and protein proteolytic degradation.” (see column 1, lines 18-37).
25. Peers et al (US Patent ‘218) teach that, “N- and C-terminal modification of peptides is common practice in the art of preparation of peptides having greater stability, particularly for in vivo use. Such modifications include the action of protecting groups such as the protecting groups used conventionally in the art of organic synthesis. Suitable N-terminal protecting groups include, for example, lower alkanoyl groups of the formula R-C(O)- in which R is a linear or branched lower alkyl…A preferred group for protecting the N-terminal end of the present compounds is the acetyl group, CH3C(O)” (see column 3, lines 15-25). The reference further teaches that “suitable C-terminal protecting groups include groups which form ketones or amides at the carbon atom of the C-terminal carboxyl, or groups which form esters at the oxygen atom of the carboxyl. Ketone and ester-forming groups include alkyl groups, particularly branched or unbranched lower alkyl” (see column 3, lines 28-33).
26. Smith et al (US Patent ‘421) teach that, “Na-acetylation is the most common chemical modification of the a-amino acid group at the amino termini of eukaryotic proteins” (see column 3, lines 62-64). Additionally, “the rate of protein turnover mediated by the ubiquitin-dependent degradation system depends on the presence of a free a-amino group at the amino terminus of model proteins and [indicates that] Na-acetylation may play a crucial role in impeding protein turnover. Thus, Na-acetylation plays important roles in regulating diverse protein functions” (see column 4, lines 21-40).
27. Therefore, it would have been obvious to one of ordinary skill in the art to have Na-acetylated and C-termini ester modified peptides for the benefit of protecting the peptide from proteolytic degradation and premature protein catabolism. One would have been motivated to acetylate the N-terminus and make an ester modification of the C-terminus, in order to mimic ‘the most common chemical modification’ of eukaryotic proteins, protect the peptide from proteolytic degradation and premature catabolism, as protecting the N- and C-terminus is 'common practice in the art' (see Peers, supra) and acetyl group is 'a very important blocking group' (Smith, supra). One would have had a reasonable expectation of success in forming these N- and C-terminal modified peptides, because it is 'common practice in the art' (Peers, supra) to modify the N-terminus with the most common chemical modification' of eukaryotic proteins (Smith, supra), and is a technique practiced widely in the art (Peers and Smith, supra).
28. Claims 50-54, 57, 59-60 and 62-69 is/are rejected under 35 U.S.C. 103 as being obvious over Ruoslahti grant W81XWH-12-1-0173 (September 2014, pp. 1-8, filed with IDS) in view of Smith et al (US Patent No. 4966848) or Peers et al (US Patent No. 5837218) or Smith et al (US Patent No. 5223421), as applied to claims above, further in view of Ruoslahti et al (US Patent No. 8367621, filed with IDS).
29. The teachings of Ruoslahti in view of Smith or Peers or Smith is described above. The difference between the references and instant claims is that the references do not teach a co-composition or a cargo, wherein the co-composition or a cargo is a pro-apoptotic agent.
30. However, Ruoslahti et al et al teach peptides useful for targeting tissue undergoing angiogenesis (see for example, abstract). Ruoslahti et al et al teach adding additional therapeutic agents, such as cytotoxic agent and pro-apoptotic polypeptides along with peptides useful for targeting tissue undergoing angiogenesis (see throughout the patent, e.g., column 21, lines 44-67 to column 22, lines 1-22).
31. Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Ruoslahti, Smith or Peers or Smith, and Ruoslahti et al to target activated cells or macrophages, since both Ruoslahti references teach peptides that target cells/macrophages. One of ordinary skill in the art would be motivated to combine with a reasonable expectation of success, since adding components known for the same purpose would at least have an additive effect. The MPEP states, “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skill in the art would have a reasonable expectation of success, since combining two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose, would have at least an additive effect.
CONCLUSION
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE HA whose telephone number is (571)272-5982. The examiner can normally be reached Monday-Thursday 5:00 am- 6:30 pm EST.
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/JULIE HA/Primary Examiner, Art Unit 1654
2/25/2026