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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/9/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 1-7 and 14 is acknowledged.
Claim 8-13 and 15-17 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as
being drawn to a nonelected, there being no allowable generic or linking claim. Election was made
without traverse in the reply filed on 7/12/2024.
Status of Claims
Withdrawn: 8-13 and 15-17
Examined Herein: 1-7 and 14
Priority
Priority to EP19157216.3 filed on 2/14/2019, EP19177667.3 filed on 5/31/2019, and
PCT/EP2020/053891 filed on 2/14/2020 is acknowledged. Receipt is acknowledged of certified copies of
papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/16/2021 and 9/1/2021 is in
compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is
being considered by the examiner.
Drawings
The drawings filed on 8/16/2021 are accepted.
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 1-7 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Vlahov (US 2019/0275181 A1, Filed 10/10/20218), in view of Wester (US 2009/0324497 A1, Published 12/31/2009).
With respect to claim 1 and 14, Vlahov discloses a PSMA binding ligand comprising a PSMA binding motif and a chelator residue represented by the following formula;
B-L-P
wherein,
B is PSMA binding ligand,
L is a divalent linker, and
P is a metal chelating group. [Vlahov, 0023]
Vlahov discloses a specific embodiment of this compound, QC08002;
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[Vlahov, Page 68]
wherein, QC0800 is a PSMA binding ligand comprising a PSMA binding motif Q (DUPA) and a chelator residue A (NOTA), wherein the PSMA binding motif and chelator residue are linked via a linker.
Vlahov further discloses L may be a linker that incorporates an oligosaccharide. [Vlahov, 0165] Vlahov also discloses the linker connects two or more functional parts of a molecule to form a conjugate, may connect the two or more functional parts at any open valence, and it is not necessary that any two or more functional parts of a molecule forming the conjugate are attached at any apparent end of the linker. [Vlahov, 0148]
Modifying the compound, QC0800, disclosed by Vlahov by replacing the linker with a linker that incorporates an oligosaccharide, results in a PSMA binding ligand comprising an oligosaccharide building block, wherein the PSMA binding ligand further comprises a PSMA binding motif Q (DUPA) and a chelator residue A (NOTA), wherein the PSMA binding motif and the chelator residue are linked via at least one linker LAQ, comprising said oligosaccharide building block, wherein the oligosaccharide building block, by definition, comprises from 3 to 10 monosaccharide units, and wherein the PMSA binding motif Q and the chelator residue A may be attached to different monosaccharide units of the oligosaccharide building block (recall, Vlahov discloses that the linker may connect the two functional parts of the conjugate (the PSMA binding motif and chelator residue) at any open valence).
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[Structure drawn by the Examiner using CAS Draw. This structure serves only as a general illustration of the result of modifying the compound, QC0800, disclosed by Vlahov by replacing the linker with a linker that incorporates an oligosaccharide]
In which case, with respect to claim 2, Vlahov discloses the modified PSMA binding ligand has the structure (I):
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wherein,
A is a chelator residue, NOTA,
LAQ, is a linker that incorporates an oligosaccharide, and
Q is a PSMA binding motif, DUPA.
With respect to claim 3, Vlahov discloses the modified PSMA binding ligand has the structure (Ia):
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71
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wherein,
A is a chelator residue, NOTA,
Q is a PSMA binding motif, DUPA, and
q is an integer of 0 and p is an integer of 0.
With respect to claim 4, Vlhaov discloses the oligosaccharide building block is an oligosaccharide. [Vlahov, 0165] An oligosaccharide comprises 3 to 10 units. Thus, the claimed range overlaps with and falls inside the range disclosed by Vlhaov.
With respect to claim 5, Vlhaov discloses the PSMA binding ligand comprises a PSMA binding motif, DUPA, and chelator residue, wherein the chelator residue is derived from NOTA. [Vlahov, Page 68]
With respect to claim 6, Vlahov discloses the chelator residue is NOTA and has the following structure;
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[Vlahov, Page 68]
With respect to claim 7, Vlahov discloses the PSMA binding ligand is DUPA. [Vlahov, Page 68]
However, Vlahov further discloses the PSMA binding ligand may be Glu-Urea-Lys, represented by the following structure;
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[Vlahov, 0223]
wherein,
R1 is H, and
R2, R3, and R4 are independently -CO2H.
Further modifying the compound, QC0800, disclosed by Vlahov by replacing the PSMA binding motif, DUPA, with Glu-Urea-Lys, results in a PSMA binding ligand comprising an oligosaccharide building block, wherein the PSMA binding ligand further comprises a PSMA binding motif Q (Glu-Urea-Lys) and a chelator residue A (NOTA), wherein the PSMA binding motif and the chelator residue are linked via at least one linker LAQ, comprising said oligosaccharide building block, wherein the oligosaccharide building block, by definition, comprises from 3 to 10 monosaccharide units, and wherein the PMSA binding motif Q and the chelator residue A may be attached to different monosaccharide units of the oligosaccharide building block (recall, Vlahov discloses that the linker may connect the two functional parts of the conjugate (the PSMA binding motif and chelator residue) at any open valence).
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[Structure drawn by the Examiner using CAS Draw. This structure serves only as a general illustration of the result of modifying the compound, QC0800, disclosed by Vlahov by replacing the linker with a linker that incorporates an oligosaccharide and the PSMA binding motif, DUPA, with Glu-Urea-Lys]
Still, Vlahov does not disclose the oligosaccharide comprises a bond being cleavable by alpha-amylase.
However, with respect to claim 1, Wester discloses a binding molecule comprising;
a ligand comprising a natural or unnatural amino acid or a peptidomimetic structure;
a carbohydrate;
a chelating group that complexes a radioisotope selected from Tc and Re. [Wester, Claim 1, 0004-0006, 0009-0012]
In one embodiment, the binding molecule is represented by the following structure:
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[Wester, Figure 1A]
wherein,
C is the chelator,
S is the carbohydrate (sugar), and
X is the C terminus of the ligand comprising a natural or unnatural amino acid or a peptidomimetic structure. [Wester, 0009-0012]
Wester further discloses the carbohydrate may be maltotriose. [Wester, 0007] Maltotriose is an oligosaccharide, which comprises a bond being cleavable by alpha-amylase.
So, Wester discloses a binding molecule comprising an oligosaccharide building block, maltotriose, which comprises a bond being cleavable by alpha-amylase, wherein said binding molecule further comprises a binding motif, a ligand comprising a natural or unnatural amino acid or a peptidomimetic structure, and a chelator residue, wherein the binding motif and the chelator residue are linked via a linker LAQ comprising said oligosaccharide building block, wherein the maltotriose comprises 3 monosaccharide units.
Modifying the compound disclosed by Vlahov so that the oligosaccharide incorporated in the linker is maltotriose, results in the PSMA binding molecule of claim 1 and pharmaceutical composition of claim 14.
It would be obvious to one of ordinary skill in the art to modify the compound, QC0800, disclosed by Vlahov by replacing the linker with a linker that incorporates an oligosaccharide and have a reasonable expectation of success. Vlahov discloses a compound, QC0800, comprising a PSMA binding ligand (DUPA) conjugated to a chelator (NOTA) via a divalent linker. Vlahov further discloses the divalent linker may be a linker that incorporates an oligosaccharide. Thus, in view of this express teaching by Vlhaov, it is reasonable to expect the compound disclosed by Vlahov may be modified by replacing the linker with a linker that incorporates an oligosaccharide. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. In the instant case, Vlahov discloses in one embodiment the linker includes a plurality of hydroxyl functional groups, such as linkers that incorporate oligosaccharides. [Vlhaov, 0165] So, the selection of a known material, a linker that incorporates an oligosaccharide, based on its suitability as a linker for use as a linker (or chain of atoms) that connects the PSMA binding motif to the chelator residue is prima facie obvious.
It would be obvious to one of ordinary skill in the art to modify the compound, QC0800, disclosed by Vlahov by replacing the PSMA binding motif, DUPA, with Glu-Urea-Lys and have a reasonable expectation of success. Vlahov discloses a compound, QC0800, comprising a PSMA binding ligand (DUPA) conjugated to a chelator (NOTA) via a divalent linker. Vlahov further discloses the PSMA binding ligand may be Glu-Urea-Lys. Thus, in view of this express teaching by Vlhaov, it is reasonable to expect the compound disclosed by Vlahov may be modified by replacing DUPA with Glu-Urea-Lys. One would have been motivated to do so because substituting equivalents known for the same purpose is prima facie obvious, when the equivalency is recognized in the prior art. In the instant case, Vlahov discloses DUPA and Glu-Urea-Lys both function as PSMA ligands. [Vlahov, 0219, 0223] So, substituting a PSMA ligand, DUPA, for another known PSMA ligand, Glu-Urea-Lys, is prima facie obvious, since the equivalency of DUPA and Glu-Urea-Lys as a PSMA ligand is recognized and disclosed by Vlahov.
It would be obvious to one of ordinary skill in the art to modify the compound, QC0800, disclosed by Vlahov so that the oligosaccharide incorporated in the linker is maltotriose and have a reasonable expectation of success because Vlahov discloses a compound, QC0800, comprising a PSMA binding ligand (DUPA) conjugated to a chelator (NOTA) via a divalent linker, wherein the divalent linker is a linker that incorporates an oligosaccharide. Similarly, Wester discloses a compound, comprising a peptide binding ligand conjugated to a chelator via a trisaccharide, maltotriose. So, Vlhaov discloses a compound comprising a peptide binding ligand conjugated to a chelator via a linker that incorporates an oligosaccharide and Wester discloses such a compound may be linked via maltotriose. Thus, the combined teachings of Vlhaov and Wester suggest that maltotriose may function as the oligosaccharide incorporated in the linker that conjugates the peptide binding ligand conjugated to the chelator in the compound disclosed by Vlhaov. Therefore, it is reasonable to expect the compound disclosed by Vlahov may be modified so that the oligosaccharide incorporated in the linker is maltotriose. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. In the instant case, Vlahov discloses, in one embodiment, the linker includes a plurality of hydroxyl functional groups, such as linkers that incorporate oligosaccharides. [Vlhaov, 0165] Wester discloses maltotriose is a trisaccharide and may be used to link a ligand or peptidomimetic to a chelator. [Wester, 0007 and Figure 1 A] A trisaccharide is a type of oligosaccharide. So, the selection of a known material, maltotriose, based on its suitability as an oligosaccharide linker for use as a linker (or chain of atoms) that connects a peptidomimetic binding motif to a chelator is prima facie obvious.
Response to Arguments
Applicant's arguments filed 11/25/2025 have been fully considered but they are not persuasive.
Applicant asserts “Vlahov neither discloses specific saccharides, such as saccharides with 3-10 monosaccharide units as claimed, nor does Vlahov disclose saccharides that are cleavable by alpha-amylases… thus, neither the problem addressed by the present invention-that salivary and lacrimal glands are severely and partially irreversibly damaged-nor a solution to this problem-providing a specific compound with a cleavable linker comprising 3 to 10 monosaccharide units-is disclosed in Vlahov.” [Remarks 11/25/2025, Page 9, Heading 1]
Applicant’s arguments are not persuasive because (1) Applicant is attempting to show non-obviousness by attacking references individually, though the rejection is based on combinations of references, (2) Applicant is arguing limitations which are not claimed, and (3) a rationale to modify a reference that is different from applicant’s is permissible.
Applicant’s assertion is limited to what Vlahov fails to teach and fails to address the combined teaching of Vlahov and Wester. However, one cannot show non-obviousness 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). Applicant’s assertion fails to show that the instant rejection is nonobvious because the test for obviousness is what the combined teachings of the references would have suggested to a POSITA. Accordingly, the Office maintains that Wester cures the aforementioned deficiencies of Vlahov for the reasons set forth in the OA of 9/5/2025.
The features (i.e., salivary and lacrimal glands are severely and partially irreversibly damaged) that Vlahov allegedly fails to address are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, it is not necessary for Vlahov or Wester to address this limitation. MPEP 2145(VI)
The reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggests achieving the same advantage or result discovered by Applicant. MPEP 2144(IV) Vhlaov’s alleged failure to address the problem and solution of the present invention does not render the rejection non-obvious because one of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.
Applicant asserts “The claimed invention provides a novel solution through alpha-amylase cleavage.” [Remarks 11/25/2025, Page 10, Heading 2]
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant asserts “The claimed invention demonstrates unexpected and advantageous results” and “Advantageously, it has been shown in the studies underlying the present invention that administration of the PSMA binding ligands and/or complexes of the present invention to a patient results in a reduced uptake of said PSMA binding ligands and/or complexes by the salivary and lacrimal glands, i.e. the patient's salivary and lacrimal glands, as compared to the uptake of e.g. the meanwhile commonly used psma-617.” [Remarks 11/25/2025, Page 10-11, Heading 2 & 3]
Applicants' arguments are not persuasive at least because the alleged unexpected results (1) fail to compare the claimed subject matter with the closest prior art and (2) are not actually unexpected.
Applicant alleges that the unexpected feature of the instant invention is larger amounts of PSMA binding ligand/complexes and higher doses of radioactivity can be administered to a patient as compared to the PSMA binding ligands/complexes described in the art. As a result, the therapeutic window is broader than with the PSMA binding ligands presently in use. However, Applicant's assertion that the claimed subject matter is advantageous over PSMA-617 and “the PSMA binding ligands and complexes described in the art” is based on “studies underlying the present invention,” rather than the claimed subject matter itself. While, Applicant compares their claimed invention against PSMA-617, the results described in the specification do not demonstrate a reduction of uptake in salivary or lacrimal glands. Thus, it appears Applicant is inferring the claimed invention possesses the allegedly unexpected feature based on effects found in underlying studies.
Moreover, Applicant asserts the claimed subject matter is advantageous over PSMA-617 and “the PSMA binding ligands and complexes described in the art.” However, Applicant has not explicitly identified what specific “PSMA binding ligands and complexes described in the art” they are referring to. Additionally, PSMA-617 is not described in the prior art relied upon by the Examiner or relied on to establish the instant prima facie case of obviousness. While, Applicants may compare a claimed invention with prior art that is more closely related to the invention than the prior art relied upon by the examiner, PSMA-617 is not more closely related to the invention than Vlahov or Wester. Thus, Applicant’s failure to compare the claimed subject matter with the closest prior art renders the allegations of unexpected and advantageous results ineffective to rebut the prima facie case of obviousness.
Furthermore, Applicant explains that the present invention removes the chelator residue A from cells of the salivary gland due to alpha-amylase activity in the saliva. As a result, the uptake of the chelator of the PSMA binding ligand in the salivary gland is reduced. As a consequence, the radio-exposition of salivary gland cells is reduced and side effects are diminished. Applicant further cites a study published in 2017, before the effective filing date of the invention, that states adverse side effects on the salivary glands are considered dosage-limiting. Thus, Applicant’s invention diminishes the side effects of radio-exposition of salivary gland cells but Kratochwil already discloses adverse side effects on the salivary glands are considered as dosage-limiting. Therefore, it is not unexpected that reducing these side effects would permit larger amounts of the claimed PSMA binding ligands and higher doses of radioactivity to be administered. The “unexpected feature” appears to be a predictable consequence of reducing the dose-limiting side effects described by Kratochwil.
Applicant asserts “Neither this problem that salivary and lacrimal glands are severely and partially irreversibly damaged-nor a solution to this problem providing a specific compound with a cleavable linker comprising 3 to 10 monosaccharide units is disclosed in Vlahov. Vlahov does not contain any teaching to provide such a compound being cleavable and, in particular, a compound which is cleaved so that PSMA binding motif and chelator are separated from each other. Wester does not remedy this deficiency.” [Remarks 11/25/2025, Page 11, Heading 4]
Applicant's arguments are not persuasive at least because (1) Applicant is arguing limitations which are not claimed, (2) a rationale to modify a reference that is different from applicant’s is permissible, and (3) Applicant has not explained why they believe Wester does not remedy the deficiencies of Vlahov.
The features (i.e., the problem that salivary and lacrimal glands are severely and partially irreversibly damaged nor a solution to this problem) that Vlahov allegedly fails to address are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, it is not necessary for Vlahov or Wester to address these features. MPEP 2145(VI)
The reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggests achieving the same advantage or result discovered by Applicant. MPEP 2144(IV) Vhlaov’s alleged failure to address the problem and solution of the present invention does not render the rejection non-obvious because one of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.
Applicant states that Wester does not remedy the deficiencies of Vlahov but this statement alone is not sufficient to rebut a prima facie case of obviousness. The Office maintains that Wester’s disclosure of maltotriose, an amylase-cleavable oligosaccharide operable as a linker in a peptide binding complex cures the deficiencies of Vlahov.
Applicant asserts “Wester is directed to fundamentally different compounds than Vlahov-namely, somatostatin receptor binding compounds. Due to the different chemical structures and applications of the compounds, it is apparent to one of ordinary skill in the art that any potential teachings disclosed in Wester do not readily apply to the compounds disclosed in Vlahov. One skilled in the art would thus not combine both teachings.” [Remarks 11/25/2025, Page 12, Heading 5]
Applicant’s assertion is not persuasive because in determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Applicant is attempting to delineate the compounds disclosed by Vlahov and Wester because they allegedly have different chemical structures and applications. However, references need not have identical chemical structures or applications to be considered by one of ordinary skill in the art. To that end, the Examiner disagrees that the difference in chemical structures between the compounds disclosed by Vlahov and Wester would render their teachings inapplicable to each other. Vlahov and Wester both disclose a peptide binding construct that employs an oligosaccharide linker to bind a chelator to a peptide binding. For this reason, the Office maintains that Wester is applicable to the compounds disclosed in Vlahov. Applicant has not identified what differences between the chemical structures and applications of the compounds disclosed in Vlahov and Wester would render Wester inapplicable to Vlahov.
Applicant asserts the following:
“The use of linkers in somatostatin receptor binding compounds does not provide guidance for selecting linkers in PSMA binding compounds, particularly where the specific property sought-alpha-amylase cleavability to reduce salivary gland toxicity-is neither disclosed nor suggested in Wester.” [Remarks 11/25/2025, Page 12, Heading 5]
“Here, neither Vlahov nor Wester suggests the use of alpha-amylase cleavable linkers, much less for the purpose of reducing salivary gland damage. One skilled in the art would have had no reason to pursue this approach absent knowledge of Applicant's invention.” [Remarks 11/25/2025, Page 12, Heading 5]
“Further, Wester does not address the problem recited in the application-that ligands may damage the salivary and lacrimal glands-nor does Wester provide a solution to this problem.” [Remarks 11/25/2025, Page 12, Heading 5]
Here, neither Vlahov nor Wester provides any suggestion that alpha-amylase cleavable linkers would be beneficial, much less any expectation that such linkers would successfully reduce salivary gland toxicity while maintaining PSMA binding and therapeutic efficacy.” [Remarks 11/25/2025, Page 13, Heading 6]
Applicant’s assertions are not persuasive because the instant rejection does not rely on Wester to establish what linkers are suitable as a linker for the PSMA binding compound disclosed by Vlahov. Vlahov already discloses that an oligosaccharide linker is suitable for the PSMA binding compound. Wester merely demonstrates that maltotriose is a specific and known oligosaccharide operable as a linker in a peptide binding construct. The instant rejection concerns the selection of a specific oligosaccharide that is operable as a linker for the general oligosaccharide linker already identified as suitable in the PSMA binding compound disclosed by Valhov. This selection does not concern or contemplate the “use of alpha-amylase cleavable linkers.” Accordingly, it is unclear why Applicant is of the opinion that the identity of the peptide binding ligand would undermine the selection of maltotriose as an oligosaccharide operable as linker in a peptide binding construct.
Moreover, one of ordinary skill in the art would not need to seek alpha-amylase cleavability, the use of alpha-amylase cleavable linkers, or any other problem, solution, property or approach described by the Applicant, when selecting a specific oligosaccharide that is operable as a linker as contemplated by Vlahov. These features are contemplated by the instant invention and it is not necessary that the prior art suggests achieving the same advantage or result discovered by Applicant. MPEP 2144(IV)
One of ordinary skill in the art would arrive at the selection of maltotriose for the reasons already described. It so happens that maltotriose is cleavable by alpha-amylase, but a POSITA would not need to consider this property to arrive at the selection. Recognizing an advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. MPEP 2145(II)
Applicant asserts "When prior art contains apparently conflicting references, the [USPTO] must weigh each reference for its power to suggest solutions to an artisan of ordinary skill." In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991). Here, the references point in different directions and provide no convergent teaching toward the claimed invention.” [Remarks 11/25/2025, Page 13, Heading 6]
It appears Applicant is referring to MPEP 2143.01(II) – “Where the teachings of two or more prior art references conflict, the examiner must weigh the power of each reference to suggest solutions to one of ordinary skill in the art, considering the degree to which one reference might accurately discredit another.”
The Office is not of the opinion that Vlahov and Wester conflict. Therefore, this framework is not applicable to the instant rejection.
Applicant asserts the following:
“One skilled in the art, faced with Vlahov's extensive catalog of linker options and Wester's disclosure in an unrelated field, would have no reason to select the specific combination of an oligosaccharide linker (1) comprising 3 to 10 monosaccharide units, (2) being cleavable by alphaamylase, and (3) being selected for the purpose of reducing salivary gland damage. This combination requires multiple selections with no guidance from the prior art and no reasonable expectation that the result would solve the dose-limiting salivary gland toxicity problem.” [Remarks 11/25/2025, Page 13, Heading 6]
“This is not a case of "obvious to try" where there exists "a finite number of identified, predictable solutions, with a reasonable expectation of success." KSR, 550 U.S. at 421. Rather, one of ordinary skill in the art faced an unpredictable field with hundreds of linker options, no teaching regarding cleavability, and no reason to expect that an alpha-amylase cleavable linker would solve the salivary gland toxicity problem.” [Remarks 11/25/2025, Page 13-14, Heading 6]
Vlahov and Wester are not in unrelated fields for the reasons described above and in the OA of 9/5/2025.
The instant claims only set forth the “combination” of (1) and (2). Applicant attempts to paint the selection of maltotriose, a species of the oligosaccharide linker genus already contemplated by Vlahov, as requiring multiple independent selections. However, the selection of maltotriose constitutes a single species selection, that necessarily encompasses element (1) and (2) because maltotriose is, by definition, an oligosaccharide comprising 3 monosaccharide units that is cleavable by alpha-amylase. Thus, this alleged “combination” recited by Applicant is merely a natural result of selecting maltotriose.
The instant rejection does not rely on the “obvious to try” principle. The instant rejection relies on the rationale that it is prima facie obvious to select maltotriose as the oligosaccharide linker in the peptide binding construct disclosed by Vlahov based on its suitability as an oligosaccharide linker because Wester discloses maltotriose is a known oligosaccharide linker in a peptide binding construct. Therefore, the “obvious to try” framework is not applicable to the instant rejection.
Conclusion
Applicant's arguments are not persuasive; therefore, the instant rejection is maintained.
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 KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618