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 .
Claim Status
Claims 1 and 8-11 are pending. Claims 2-7 were canceled; claims 1 and 8-9 were amended; and no new claims were added in the reply filed 1/27/2026. Claims 10-11 remain withdrawn. Claims 1 and 8-9 are presently considered.
Election/Restriction
Applicant’s election of Group I (claims 1-9) and the species of DHA-ACP52C at Figure 16 in the reply filed on 9/29/2025 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)).
The originally elected species is understood to be
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Accordingly, the originally elected species is understood to SEQ ID NO: 8 (GGNYPQRPCRGDKGPDC) conjugated to the unsaturated fatty acid of DHA (all-cis-docosa-4,7,10,13,16,19-hexa-enoic acid) via a glycine, wherein SEQ ID NO: 8 is understood to comprise the cell-penetrating peptide (CPP) of SEQ ID NO: 3 (CRGDKGPDC); the CP2c-targeting peptide of both SEQ ID NO: 2 (NYPQRP) and SEQ ID NO: 1 (YPQR); having a modified C-terminus comprising an amide group; and having a G2 linker at the N-terminus.
Following extensive search and examination, the originally elected species was previously deemed anticipated and/or obvious in view of the prior art as applied in the Action mailed 10/28/2025. In the Reply filed 1/27/2026, the claims were substantially amended and/or canceled. However, claims 1 and 8-9, as filed 1/27/2026, are understood to continue reading upon the originally elected species.
Accordingly, the originally elected species has been considered a second time. Following extensive search and examination, the originally elected species has again been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 10-11 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claims 10-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/29/2025.
Claims 1 and 8-9 are presently considered.
Priority
The priority claim to KR10-2020-0013901 (filed 02/05/2020) and PCT/KR2021/000847 (filed 1/21/2021) are acknowledged.
Examiner notes that no certified translation of the Foreign Application KR10-2020-0013901 (filed 02/05/2020) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
No IDS was filed with the 1/27/2026 reply.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111.
Amended claim 1 is representative of the pending claim scope and is directed a genus of compounds “comprising” the structures set forth therein, which is understood to continue reading upon the originally elected species. Additional claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)).
A health functional food composition is interpreted in view of the disclosure (see, e.g., Spec. filed 8/03/2022 at 11 at line 15 to p. 13 at line 3).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 3-4 and 7 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn as moot in view of the cancellation of claims 3-4 and 7.
The rejection of claims 1-5 and 8-9 under 35 U.S.C. 103 as being unpatentable over US2018/0086788A1 (Mar. 29, 2018) in view of Menacho-Melgar et al1 is withdrawn in view of the cancellation of claims 2-5 and amendments to claims 1 and 8-9 as filed 1/27/2026. Revised rejections relying upon the teachings of one or more of these references has been set forth below, as necessitated by Applicant’s amendments.
The rejection of Claims 1-9 under 35 U.S.C. 103 as being unpatentable over US2018/0086788A1 in view of Menacho as applied to claims 1-5 and 8-9 above, and further in view of Swiecicki et al.2 is withdrawn in view of the cancellation of claims 2-7 and amendments to claims 1 and 8-9 as filed 1/27/2026. Revised rejections relying upon the teachings of one or more of these references has been set forth below, as necessitated by Applicant’s amendments.
The rejection of claims 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0086788A1 in view of Menacho and Swiecicki et al. as applied to claims 1-9 above, and further in view of Lee3 is withdrawn in view of the cancellation of claims 2-7 and amendments to claims 1 and 8-9 as filed 1/27/2026. Revised rejections relying upon the teachings of one or more of these references has been set forth below, as necessitated by Applicant’s amendments.
The rejection of claims 1-9 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 11-12 of U.S. Patent No. 10,611,797 B2 (corresponding to US2018/0086788A1 applied in preceding rejections) in view of Menacho and Swiecicki et al. is withdrawn in view of the cancellation of claims 2-7 and amendments to claims 1 and 8-9 as filed 1/27/2026.
New or Revised Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 103
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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
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.
Claims 1 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Lee4 in view of US2018/0086788A1.
Claim interpretation: The applicable claim interpretation has been set forth in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Lee pertains to derivatives of peptides capable of inhibiting CP2 complex formation, usable in the treatment of cancer (see, e.g., Lee at abstract at III-IV, 2 at 1st full ¶). Regarding instant amended claim 1 and the originally elected species of “DHA-ACP52C”, Lee teaches that peptides that inhibit CP2c complex formation may be conjugated to iRGD cell penetrating peptides having the sequence of CRGDKGPDC (see, e.g., Lee at abstract at III-IV, 2 at 1st full ¶, Fig. 2(a)-(b) on 24; compare id. with instant SEQ ID NO: 3, showing 100% identity), and that such peptides may also be advantageously conjugated to docosahexaenoic acid (DHA) to increase lipophilicity, improve drug delivery, and improve tumor targeting, and to reduce toxicity (see, e.g., Lee at 3 at 1st full ¶, Fig. 2(a)-(b) on 24). Lee exemplifies such compounds by directing artisans to a partially-disclosed DHA-conjugated ACP52 peptide derivative referred to as “DHA-ACP52C”, which has the following structure
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(see, e.g., Lee at Fig. 2(a)-(b) on 24), wherein the non-disclosed 6-amino acids (“X-X-X-X-X-X”) correspond to “ACP52” and are conjugated to the “iRGD” sequence of CRGDKGPDC-NH2, and linked via a GG linker via a carboxyl group to the unsaturated fatty acid of DHA (see id). Regarding instant claims 1, 8-9, and the utility of DHA-ACP52C, Lee informs artisans that the structure of “ACP52C” is a peptide-based compound capable of treating cancer by suppressing the activity of CP2c an anticancer agent (see, e.g., Lee at abstract at III-IV), and Lee reports that the DHA-conjugated peptide improved treatment of cancer cells in culture (see, e.g., Lee at 14-15 at bridging ¶, Fig. 2(a)-(b) on 24).
Lee differs from amended claims 1 and 8-9 as follows: Although Lee discloses a DHA-conjugated ACP52 peptide that appears identical to the originally elected species, Lee does not actually disclose the 6-amino acid sequence of “XXXXXX” within the structure is or otherwise may be instant SEQ ID NO: 2 (NYPQRP).
Although silent regarding the identity of “XXXXXX” within the structure of DHA-conjugated ACP52C5, Lee provides explicit guidance permitting an artisan to reasonably identify the peptide or a functionally equivalent peptide. Specifically, Lee identifies that the “XXXXXX” sequence refers to “A derivative of peptide #5 with 6 amino acids (ACP52)” (see Lee at 2 at 1st full ¶), which was conjugated to the cell penetration peptide of “iRGD” (CRGDKGPDC) (see id), wherein the conjugate was identified as useful for treating cancer by suppressing the activity of CP2c (see, e.g., Lee at abstract at III-IV), and wherein the peptide is identified by reference to a “previous study of our lab” (see Lee at 2 at 1st full ¶). This is pertinent because “our lab” would be understood to refer to the Lab of the Thesis Supervisor identified in Lee, which was Chul Geun Kim. Accordingly, an artisan would reasonably appreciate that “X-X-X-X-X-X” referred to a 6-mer “derivative of peptide #5 with 6 amino acids” that had been conjugated to CRGDKGPDC and was disclosed as capable of binding to transcription factor CP2c, and usable to treat cancer, wherein the peptide would also be associated with Chul Geun Kim (see, e.g., Lee at 2 at 1st full ¶, abstract at III-IV). An artisan with this information would review the prior art and be directed to US2018/0086788A1.
Regarding instantly amended claims 1, 8-9, and instant SEQ ID NO: 2(NYPQRP), US’788 names as an inventor Chul Geun Kim, and discloses and claims a 6-mer polypeptide having the sequence “NYPQRP”, which was disclosed as capable of binding to transcription factor CP2c and capable of treating cancer (see, e.g., US’788 at title, abs, ¶¶[0006]-[0009], claims 1-4 and 11-12, SEQ ID NO: 2), which was conjugated to the cell penetration peptide of “iRGD” (CRGDKGPDC) (see, e.g., US’788 at claims 1 and 3). Furthermore, as described by Lee, the sequence of NYPQRP is identified as a derivative of “peptide#05” (see, e.g., US’788 at Fig. 1, noting that NYPQRP corresponds to the C-terminus of “peptide#05”; compare id. with Lee at 2 at 1st full ¶). Accordingly, given the identifying description of Lee, an artisan would readily conclude that the “X-X-X-X-X-X” 6-mer polypeptide of “DHA-ACP52C” disclosed by Lee (see, e.g., Lee at Fig. 2(a)-(b) on 24) was NYPQRP as disclosed by US’788, or otherwise that NYPQRP was functionally equivalent of the undisclosed 6-mer of Lee6. Regarding instant claims 8-9, US’788 explicitly directs and informs artisans that compounds comprising NYPQRP may be utilized in pharmaceutical compositions and within “health functional food compositions” (see, e.g., US’788 at claims 1, 3-4, and 11-12).
Accordingly, the relevant question is whether or not it would have been obvious to simply substitute the undisclosed “XXXXXX” peptide of Lee in the prior art species of DHA-ACP52C with “NYPQRP” as taught by US’788 with a reasonable expectation that the resulting conjugate would continue to act as an anticancer agent capable of inhibiting or suppressing CP2c activity. Stated alternatively, the question is whether or not an artisan would reasonably substitute the US’788 polypeptide of
NYPQRPCRGDKGPDC-NH2
in place of
XXXXXXCRGDKGPDC-NH2
within the structure of DHA-ACP52 as disclosed by Lee (see, e.g., Lee at Fig. 2(a)-(b) on 24) to predictably obtain
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In view of the fact that both Lee and US’788 teach and disclose anticancer agents that suppress the activity of CP2c (compare Lee at abstract at III-IV with US’788 at title, abs, claims 1-3 and 11-12, ¶¶[0001], [0005]-[0006], [0018], [0041], [0043]-[0044], [0050]-[0053]), and appear to be the same (see discussion above), an artisan would readily appreciate that simply substituting in the peptide of US’788 in place of “XXXXXX” of Lee would predictably and desirably result in a compound capable of treating cancer as taught and suggested by US’788 and Lee, wherein the resulting DHA-peptide-conjugate would have the benefits and applications taught by both US’788 and Lee (see, e.g., Lee at abstract at III-IV, 2 at 1st full ¶; US’788 at claims 1-4 and 10-11).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the simple substitution of one CP2c activity suppressing peptide (i.e., NYPQRP, SEQ ID NO: 1 of US’788) in place of an undisclosed CP2c activity suppressing peptide in the DHA-ACP52 compound of Lee (i.e., XXXXXX), wherein such simple substitution would yield predictable results, namely a compound having the structure of
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,
wherein such structure would predictably and expectedly exhibit the anticancer activities described by US’788 and attributed to CP2c suppressing peptides by Lee, and additionally exhibit the benefits of the DHA lipid as disclosed by Lee (e.g., improved half-life) as taught and suggested by Lee (see, e.g., MPEP § 2143(I)(B), (G)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to simply substitute a know CP2c suppressing polypeptide, known in the prior art, for another undisclosed CP2c suppressing polypeptide having the same length and reported functionality, within a known structure to predictably obtain the exact result taught, suggested, and predicted by the prior art, namely a peptide having the structure of [DHA]-C(O)-GGNYPQRPCRGDKGPDC-NH2, wherein such modified polypeptide exhibits the exact improvements taught and expected in view of the prior art, and the same utility attributed to it by the prior art.
Accordingly, claims 1 and 8-9 are rejected.
Response to Arguments
Applicant’s arguments with respect to amended claims 1 and 8-9 have been fully considered but are substantially rendered moot in view of the new or revised rejections set forth above. The new or revised rejections rely on references of record for teachings of record, and remaining applicable arguments are addressed below.
All rejections pertaining to canceled claims or rejections in view of the teachings of Menacho or Swiecicki are moot.
Applicant raises applicable arguments at pages 7-12 (see, e.g., Reply filed 1/27/2026 at 7 at final three ¶¶ to page 12 at final ¶), which are addressed below.
Applicant addresses references individually: It is the Examiner’s understanding that Applicant addresses the teachings of the references individually rather than in combination (see, e.g., Reply filed 1/27/2026 at 7-8 at bridging ¶). In response to applicant's arguments against the references individually, 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). The differences identified by Applicant are taught in view of the combination, not the individual references.
Applicant alleges that the prior art does not teach an unspecified limitation or component: It is the Examiner’s understanding that Applicant is alleging that the prior art does not teach “[t]his specific combination of features . . . individually or in combination” (see, e.g., Reply filed 1/27/2026 at 7 at ¶ starting with “This specific”), but fails to identify a single aspect of the amended claim scope that is not fully addressed by US’788 and Lee. Accordingly, such arguments are not persuasive because they amount to an argument of counsel unsupported by objective evidence.
Applicant alleges improper hindsight reasoning: It is the Examiner’s understanding that Applicant is alleging that the Examiner relied upon improper hindsight reasoning (see, e.g., Reply filed 1/27/2026 at 8 at 1st full ¶). In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not taught or disclosed by the prior art.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging that there would not be a reasonable expectation of success due to lack of predictability in the peptide modification arts (see, e.g., Reply filed 1/27/2026 at 8 at 1st full ¶ to 2nd full ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “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 would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Applicant alleges lack of motivation to arrive at the instantly claimed invention: It is the Examiner’s understanding that Applicant is alleging that “there is no teaching or motivation in the asserted references to combine these specific elements” (see, e.g., Reply filed 1/27/2026 at 8 at 1st full ¶). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, 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). In this case, the Examiner’s rationale for arriving at the claimed invention is explicitly set forth in the rejection above and of record, namely the rationales set forth at MPEP § 2143(I)(B) and (G). Applicant fails to acknowledge or specifically address these rationales, or explain why simply substituting the 6-mer CP2c activity suppressing peptide of US’788 (i.e., NYPQRP) into the undisclosed 6-mer peptide portion of the DHA-ACP52 construct of Lee would not predictably and expectedly yield a structure within the scope of instant claim 1, which would be expected and predicted to have the anti-cancer functionalities and benefits described by the prior art. Accordingly, a clear rationale supporting a determination of obviousness was placed on record and was not addressed by the Applicant. Accordingly, such arguments are not persuasive.
Applicant attempts to rely upon a partial quote unsupported by objective supporting evidence: It is the Examiner’s understanding that Applicant directs the Examiner to Figure 11 and alleges that “Both conjugates showed efficacy that was ‘significantly less than that of . . .ACP52C’” (see, e.g., Reply filed 1/27/2026 at 9 at 1st full ¶). No citation is provided, but upon review the quote is understood to come from the Specification and is based upon Figure 11 (see, e.g., Spec. filed 8/03/2022 at 21 at lines 22-25). Upon review of Figure 11, it is noted that Figure 11(B) shows indistinguishable grey dots for each compound and therefore does not provide reasonable means of distinguishing which lines correspond to any particular sample. Upon review of Figure 11(D), it is noted that p-values indicative of statistical significance are shown relative to the “mock” and “sorafenib” samples, but no identification of statistical significance between ACP52CK, ACP52CG, and ACP52C is actually shown. Accordingly, the quoted portion (see, e.g., Reply filed 1/27/2026 at 9 at 1st full ¶; quoting Spec. filed 8/03/2022 at 21 at lines 22-25) appears to not refer to a comparison of these compounds, or otherwise the phrase “significantly less than” is used in a non-scientific or non-statistical sense. Furthermore, such data appears to be substantially identical to the data of Lee (compare instant Fig. 11 with Lee at Fig. 8 on 37, Figures 9(A)-(F) on 39-41, Fig. 10(A)-(F) at pages 43-45), and is therefore the expected and predicted results in view of the prior art. However, even assuming arguendo and in the light most favorable to the Applicant that ACP52C performed statistically better than two other tested compounds, the invention would remain obvious because the prior art of Lee in view of US’788 provides explicit guidance directing artisans to specifically utilize a compound satisfying the identifying description of Lee, wherein an artisan would readily conclude that the “X-X-X-X-X-X” 6-mer polypeptide of “DHA-ACP52C” disclosed by Lee (see, e.g., Lee at Fig. 2(a)-(b) on 24) was either NYPQRP as disclosed by US’788, or otherwise an artisan would conclude that NYPQRP was functionally equivalent to the undisclosed 6-mer of Lee7. In view of such direct guidance to the exact structure claimed, the evidence of record weighs in favor of a determination of obviousness. In sum, this argument has been fully considered, but not found persuasive.
It is the Examiner’s understanding that Applicant is alleging unexpected and superior results sufficient to rebut prima facie obviousness: It is the Examiner’s understanding that Applicant repeatedly alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed 1/27/2026 at 9 at § “2” to page 12 at 3rd full ¶). However, to establish such unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). As an initial matter, the proffered data fails to provide a comparison with the closest existing prior art of record as required by MPEP § 716.02(e)(I)-(II), which are lipidated peptides of Lee. Second, the proffered data is not commensurate in scope with the instant claims, which more broadly encompasses compounds “comprising” such components at claim 1, but permitted to include additional structures. Third, per MPEP § 716.02(c)(II), "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof", and here the proffered data appears to be identical to the data disclosed by Lee (compare Reply filed 1/27/2026 at 9 at § “2” to page 12 at 3rd full ¶ with Lee at Fig. 8 on 37, Figures 9(A)-(F) on 39-41, Fig. 10(A)-(F) at pages 43-45), and the prior art of Lee explicitly teaches and identifies that the DHA-ACP52C structure would advantageously and predictably have improved efficacy in vivo and an extended half-life relative to unconjugated ACP52C (see, e.g., Lee at abstract at III-IV). Accordingly, the proffered data appears to show exactly what would be expected and predicted to occur in view of the prior art, wherein the undisclosed sequence of Lee would be readily understood to either (i) be NYPQRP as disclosed by US’788, or (ii) be readily understood by an artisan to be functionally equivalent to NYPQRP as disclosed by US’788. Therefore, allegations of unexpected results premised upon achieving the exact results suggested and disclosed by Lee weighs in favor of a determination of obviousness rather than non-obviousness (see, e.g., MPEP § 716.02(c)(II)). Accordingly, no evidence commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02 sufficient to rebut prima facie obviousness has been placed on record to date.
In sum, all applicable arguments have been fully considered but not found persuasive at this time. Accordingly, the amended claims are rejected in view of the new/revised rejection set forth above. All new/revised rejections were necessitated by Applicant’s amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lim8 explains that a well-known limitation on the utility of therapeutic proteins is their short serum half-life (see, e.g., Lim at 219 at col I at 1st ¶). Lim explains that an art-recognized solution for this problem includes modifying a therapeutic protein to include a ligand for human serum albumin (see, e.g., Lim at 219 at col I-II at bridging ¶). Accordingly, conjugating fatty acids to polypeptides was an art-recognized means to improve protein half-life in vivo (see, e.g., Lim at title, abs), presumably by binding to albumin in vivo (see, e.g., Lim at title, abs, 219-220 at bridging ¶, 224 at col I at 2nd full ¶).
Menacho-Melgar et al9 establishes that an artisan would appreciate that fatty acids are understood to be lipids (see, e.g., Menacho at 6 at col I at 2nd full ¶, discussing “fatty acid chain length”, 6 at col II at 1st full ¶ and final ¶, 9 at col II at 3rd full ¶). Menacho reviews lipidation of peptide therapeutics (see, e.g., Menacho at title, abs), and identifies that lipidation desirably and predictably provide multiple benefits, including improving half-life, reducing immunogenicity, improving intracellular uptake, and delivery across epithelia (see, e.g., Menacho at abs, 2 at col II at 1st full ¶, 3 at § 1.1 at col I at 1st ¶, 4 at § 1.2 at col I at 1st to 3rd ¶¶, 4 at § 1.3 at col II at final ¶, 7 at § 1.5 at col I-II at bridging ¶). Menacho identifies that unsaturated lipids bonds do not impact albumin bindings (see, e.g., Menacho at 3 at col II at final ¶), and that “unsaturated lipids as opposed to saturated ones can increase relative rates of direct translocation because they can interfere with membrane packing to a higher extent” (see, e.g., Menacho at 4 at col II at 1st full ¶). Accordingly, Menacho identifies that unsaturated lipids had art-recognized advantages relative to saturated lipids. Menacho identifies that linkers may be utilized to conjugate lipids to therapeutic polypeptides, including peptide based linkers (see, e.g., Menacho at 6 at col I at § 1.4 to col II at 2nd full ¶).
Swiecicki et al.10 pertains to a proof-of-principle regarding lipopeptides wherein an oligopeptide was conjugated to unsaturated fatty acids (see, e.g., Swiecicki at title, abs). Swiecicki establishes that an all cis unsaturated chain (C22:6) facilitated direct translocation of the oligopeptides when conjugated to the N-terminus via a carboxyl group of the unsaturated fatty acid (see, e.g., Swiecicki at abs, 14656 at col II at 1st to 2nd ¶¶, 14657 at Scheme 1 and Fig. 1; compare id. with instant claims 6-7). The all cis unsaturated chain (C22:6) is identified as docosahexanoic acid (see, e.g., Swiecicki at abs, 14656 at col II at 1st to 2nd ¶¶, 14657 at Scheme 1, reproduced in part below):
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543
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Accordingly, lipidation was a known process taught in the prior art by Menacho, and such methods of lipidation utilizing N-terminally linked all-cis docosahexanoic acid was also known in the prior art.
U.S. Patent No. 10,611,797 B2 claims the CP2c-targeting peptide of NYPQRP (i.e., instant SEQ ID NO: 2) conjugated to instant SEQ ID NO: 3 (i.e., CRGDKGPDC), to form “NYPQRPCRGDKGPDC”, wherein it is understood in view of US’797 at claim 2 that the structures of claim 1 may be amidated at the C-terminus, which is usable in pharmaceutical and functional health food compositions for the treatment of cancer (compare US’797 at claims 1-3 and 11-12 with instant claims 1-5 and 8-9).
US 20220160888 (corresponding to US Application 17/600,760) pertains to similar compounds conjugated via a different linkage to a different lipid moiety (see, e.g., US’888 at claims). A notice of allowance was mailed in the corresponding Application on 12/17/2025, and the Issue Fee was paid on 2/27/2026.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Menacho-Melgar et al., A review of lipidation in the development of advanced protein and peptide therapeutics. J Control Release. 2019 Feb 10;295:1-12. doi: 10.1016/j.jconrel.2018.12.032. Epub 2018 Dec 21. PMID: 30579981; PMCID: PMC7520907; hereafter “Menacho”; cited in previous action.
2 Swiecicki et al., Unsaturated acyl chains dramatically enhanced cellular uptake by direct translocation of a minimalist oligo-arginine lipopeptide. Chem Commun (Camb). 2015 Oct 7;51(78):14656-9. doi: 10.1039/c5cc06116d. PMID: 26291669; hereafter “Swiecicki”; cited in previous action.
3 Jin Youn Lee, “Effects of DHA-conjugation on the anticancer function of CP2c-targeting peptide”, Thesis for the Master of Science, Graduate School of Hanyang University, August 2019, pp. 1-47; cited in IDS filed 8/03/2022 as cite No. 6; hereafter “Lee”.
4 Jin Youn Lee, “Effects of DHA-conjugation on the anticancer function of CP2c-targeting peptide”, Thesis for the Master of Science, Graduate School of Hanyang University, August 2019, pp. 1-47; cited in IDS filed 8/03/2022 as cite No. 6; hereafter “Lee”.
5 See, e.g., Lee at abstract at III-IV, 2 at 1st full ¶, Fig. 2(a)-(b) on 24.
6 See, e.g., MPEP § 2141, explaining that “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396.
7 See, e.g., MPEP § 2141, explaining that “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396.
8 Lim et al., Site-specific fatty acid-conjugation to prolong protein half-life in vivo. J Control Release. 2013 Sep 10;170(2):219-25. doi: 10.1016/j.jconrel.2013.05.023. Epub 2013 Jun 2. PMID: 23735573; PMCID: PMC4437666; cited in Restriction/Election Requirement.
9 Menacho-Melgar et al., A review of lipidation in the development of advanced protein and peptide therapeutics. J Control Release. 2019 Feb 10;295:1-12. doi: 10.1016/j.jconrel.2018.12.032. Epub 2018 Dec 21. PMID: 30579981; PMCID: PMC7520907; hereafter “Menacho”; cited in previous action.
10 Swiecicki et al., Unsaturated acyl chains dramatically enhanced cellular uptake by direct translocation of a minimalist oligo-arginine lipopeptide. Chem Commun (Camb). 2015 Oct 7;51(78):14656-9. doi: 10.1039/c5cc06116d. PMID: 26291669; hereafter “Swiecicki”; cited in previous action.