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 .
Election/Restrictions
Applicant’s election without traverse of group 1 and FAP-3000 in the reply filed on July 20, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claims 109 – 111 were mistakenly included in group I and as they are directed to methods, only are present in non-elected groups II and III and not in group I.
The elected species was found to be free of the prior art and the search was expanded to the compounds discussed in the obviousness rejections below.
Drawings
The drawings are objected to because of various issues with clarity. For example, in Figured 3A – 3D, there is text in gray scale areas that is difficult to read. Structures in Figure 20A and 27 (p 44 of the drawings) are blurry and difficult to read. A typographical error appears to be present in Figure 23A. This is not an exclusive list of all issues and all figures should be reviewed for additional issues not specifically called out. 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.
Specification
The disclosure is objected to because of the following informalities: the quality of some chemical structures in the specification is low such the features of the structures, particularly subscripts or superscripts, cannot readily be read. All chemical formulas should be reviewed for legibility.
Appropriate correction is required.
Claim Objections
Claim 21 is objected to because of the following informalities: DOTA is not accompanied by the complete chemical name the first time it is used in the claims, which is actually present a separate item in the Markush group as DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 28 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 28 requires portion A of the compound of claim 1 to have a binding affinity to FAPα from about 1 nM to about 25 nM. The claim language does not require the compound as a whole, but the one portion of the compound, to have such an affinity.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus.
Example 2 in the specification as filed sets forth how binding affinities were determined with the inhibition constants being determined and reference made to Figures 6A and 6B, which appears to be a typographical error as bar graphs with dissociation constants are in Figures 4A and 4B. Only two compounds – both with 111In bound were tested and the labeled elected species FAP-3000 had a Kd of 1.2 nM, falling within the claimed while that os FAP-3001 had a Kd of 0.92 nM, which may or may not be within the scope of the claimed range given the use of the word “about”. It is noted that there is a definition of “about” set forth at ¶ [0700] of the PGPub of the instant application but the nature of the definition makes it unclear if 0.92 nM would be considered to be about 1 nM. The data in Figure 2A – 2G covers more compounds but determines the inhibition constant, not the binding constant as required by this claim.
Both of the compounds tested have the same ring system defined in claim 1 as A, although certain dependent claims include additional parts of the FAP-3000 and FAP-3001 molecules in A that are different but this affects their binding affinities (see below for additional discussion). This suggests that portions of the molecule outside of A influence the binding constant as the terminal portions of these compounds are the same. There does not appear to be a known structure function relationship between this portion of the molecule and binding affinity to FAPα that would aid one of ordinary skill in the art in determining what values for A of the claimed compounds would result in the required binding affinity required by this claim.
At most two compounds were disclosed that are not necessarily different in A that affects the binding affinity. The disclosure as originally filed does not disclose a representative number of species within the claimed genus to demonstrate possession of the full scope of compounds of claim 1 with an A portion having a binding affinity to FAPα from about 1 nM to about 25 nM to completely satisfy the written description.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 1, 2, 7, 10, 12, 14, 16, 17, 18, 21, 28 – 31, 47, 66 and 108 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.
Several of the variable definitions set forth in claim 1 result in scope of the compounds of formula (X) and therefore what constitutes a proper dependent claim being unclear.
J, which is a divalent moiety, is defined as C(RJ)0-3 where one option is that “two or more of RJ are taken together to form oxo”. Oxo would be a double bonded oxygen atom that together with the C would be a carbonyl moiety. But this group cannot result from two separate substituents being taken together as set forth in this definition. Such phrasing is often used when two substituents can be separate or joined together to form a ring, but that is not the scenario of claim 1. Therefore the scope of J cannot be determined.
R1 and R2 are terminal groups on one of the pyrrolidine rings and amongst the possible groups for these variables is “-C(O)aryl-“ which would be understood by one of ordinary skill in the art to required bonds on either end, with the “-C(O)alkyl” only requiring one point of attachment. What is required to be present on the non-carbonyl side of the aryl ring for this option for R1 and R2 cannot be determined.
The dependent claims fall therewith.
Please clarify.
Claims 1 and 10 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.
Regarding claims 1 and 10, “e.g.”, which means "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Please clarify.
Claims 2, 31 and 47 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. Each claim contains a limitation regarding (PEG)n and the lower limit for n is 0, which results in this option not being anything. Is there some other meaning of n being used that has not been specified that renders n = 0 to be an actual compound? Please clarify.
Claim 7 is 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.
The structure in this claim is blurry and it makes discerning detail such as which variable comprises a apostrophe difficult.
The definitions of P and the ascribed function for this variable do not appear to be chemically possible. P is described as the “point of attachment to L or B’”. In formula (X) of Am-L-B’ in claim 1, from which claim 7 depends, there is no indication that L is optional so it is not clear how the A moiety defined in this claim could attach to B’. Claim 7 then goes on to provide a Markush group of options for P, none of which are specifically called out as divalent as would be required for the P group to be attached to ring of formula (X-Y) as set forth in claim 7 and either L or B’. Groups such as -H, -OH, -NH2 and -CONH2 are just several examples of specific values for P recited that cannot serve as the attachment point as also required by the claims.
Please clarify.
Claim Rejections - 35 USC § 112 – Failure to Further Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 14 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Each of these claims depends from claim 1 and further defines A, which in claim 1 is formula (X-B). However, the structures set forth in each of these contains additional elements (a triazole ring in claim 14 and triazole ring and benzene ring in claim 16) that do not fall within the scope of A as defined in claim 1 and the apparent possible values for J, that indicate attachment to linker L. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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, 2, 10, 12, 18, 21, 28 – 31, 47 and 108 are rejected under 35 U.S.C. 103 as being obvious over Yang et al. (WO 2019/083990) in view of Jiaang et al. (US 8,071,787).
Yang et al. discloses imaging and radiotherapeutic agents targeting fibroblast activating protein-α (FAPα) (whole document, e.g., abstract). The compounds have a general formula as shown on p 2, ln 10 of B-L-A, wherein A is a targeting moiety for FAPα, L is a bifunctional linker adapted to form chemical bonds with A and B and B is any optical or radiolabeled functional group suitable for optical imaging, PET imaging, SPECT imaging or radiotherapy (p 2, ln 10 – 16). A structure of the FAPα targeting moiety is the structure shown on p 2, line 18 of formula (X’). Examples of suitable linkers L begin on p 15, ln 18 and include those that could be releasable as they contain amide bonds that are cleavable (e.g., the first compound in line 7 on p 16) and therefore releasable or those that are not cleavable (e.g., the first compound in line 6 on p 16) and therefore would not be releasable. The second structure on p 16, ln 8 comprises ethylene oxide groups, with u being an integer from 1- 8, reading on the linker comprising PEG that overlaps with the range of the instant claims. As to B, suitable groups are disclosed beginning at p 17, ln 4 and can be radiolabeled with suitable radionuclides disclosed on p 17, ln 5 onward). Chelating agents that include DOTA are specifically exemplified for B at p 17, ln 15 onward. Pharmaceutical compositions of the compounds are also disclosed beginning on p 23, ln 2.
A FAP binding portion as required by the instant claims is not disclosed.
Jiaang et al. discloses pyrrolidine compounds of the formula set forth in the abstract for inhibiting the activity of FAP. Amongst the specific FAP binding compounds disclosed by Jiaang et al. is compound 3 at the top of column 3 that corresponds to formula (X-B) and the A portion of the elected species as a FAP binding moiety.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use compounds disclosed by Jiaang et al. such as compound 3 as the FAP binding portion of the conjugates disclosed by Yang et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because various structures are known in the art for binding to FAP such as the compounds disclosed by Jiaang et al. The use of such moieties in the conjugates of Yang et al. will allow for imaging and/or radiotherapy using the compounds that target FAP. Given the difference in structure for the different FAP binding moieties, the different conjugates would exhibit slightly different behaviour such as binding affinity to FAP and there is no evidence of record of unexpected results arising from the presently claimed FAP binding portion of the molecule.
As to claim 28, the binding affinity of the conjugates or compounds in Jiaang et al. is not disclosed but aligns with the A portion of FAP-3000 whose binding affinity lies within the claimed range. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. and Jiaang et al. as applied to claims 1, 2, 10, 12, 18, 21, 28 – 31, 47, and 108 above, and further in view of Pickens et el. (Bioconjugate chemistry, 2018).
Yang et al. and Jiaang et al. are discussed above.
The presence of a triazole ring is not disclosed.
Pickens et al. discloses the azide-alkyne cycloaddition (AAC) reaction that results in the formation of a 1,2,3-traizole ring (e.g., abstract). As shown in Figure 1, click chemistry reactions provide a toolbox for efficient coupling methods to synthesize of a variety of conjugates (p 686, col 1, ¶ 1 and Figure 1). The 1,2,3-triazole ring is an attractive biasteric replacement for amides (sentence bridging p 686 and 687). The AAC reaction in particular is poised to enable a large set of functionalized molecules as a combinatorial approach to high-throughput bioconjugate generation, screening, and honing of lead compounds (abstract).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAC click chemistry to prepare the conjugates of Yang et al. with the FAP binding moiety of Jiaang et al. that will result in a triazole ring being present in the final conjugate. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the AAC click chemistry reaction is taught by Pickens et al. as useful for the preparation of a variety of conjugates and is an efficient coupling reaction.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 7, 10, 12, 14, 16, 17, 28 – 31, 47 and 108 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 41 – 65, 68, 69, 71 – 79 of copending Application No. 17/761,508 (reference application) optionally further in view of Pickens et el. (Bioconjugate chemistry, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’508 and the instant application encompass overlapping compounds. The compounds of claim 1
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of US’508 are defined in manners that overlap with the instant claims. Methods of using such compounds are also present. The claims of the instant application are not patentably distinguished over those of US’508.
The presence of a triazole ring is not claimed.
Pickens et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAC click chemistry to prepare the conjugates of US’508 will result in a triazole ring being present in the final conjugate. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the AAC click chemistry reaction is taught by Pickens et al. as useful for the preparation of a variety of conjugates and is an efficient coupling reaction.
As to claim 28, the binding affinity of the conjugates or compounds in Jiaang et al. is not disclosed but aligns with the A portion of FAP-3000 whose binding affinity lies within the claimed range. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 7, 10, 12, 14, 17, 18, 21, 28 – 31, 47 and 108 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 27 of copending Application No. 18/336,708 (reference application) optionally further in view of Pickens et el. (Bioconjugate chemistry, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are not patentably distinct from each other because the claims of US’708 and the instant application encompass overlapping compounds. The claims are drawn to conjugates, compositions of such conjugates and methods of using the conjugates for imaging with the general structure (a radical of a small molecule ligand that specifically binds with fibroblast activation protein (FAP))-Linker-(radical of a magnetic resonance imaging (MRI) agent) (claim 1). The FAP binding portion aligns with that portion of the instant claims as shown in claims 2 - 5. Claims 6 and 7 provide options for the linker. Claims 8 - 25 relate to the MRI agent and possible values that overlap with the instant claims such as DOTA (e.g., claim 11). The claims of the instant application are not patentably distinguished over those of US’708.
The presence of a triazole ring is not claimed.
Pickens et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAC click chemistry to prepare the conjugates of US’708 that will result in a triazole ring being present in the final conjugate. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the AAC click chemistry reaction is taught by Pickens et al. as useful for the preparation of a variety of conjugates and is an efficient coupling reaction.
As to claim 28, the binding affinity of the conjugates or compounds in Jiaang et al. is not disclosed but aligns with the A portion of FAP-3000 whose binding affinity lies within the claimed range. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 7, 10, 12, 14 17, 18, 21, 28 – 31, 47 and 108 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 46 of copending Application No. 19/606,845 (reference application) optionally further in view of Pickens et el. (Bioconjugate chemistry, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because they are not patentably distinct from each other because the claims of US’845 and the instant application encompass overlapping compounds. The compounds of US’845 have a ligand F that binds to FAPα, a pharmacoextender that binds to a protein in the blood and a chelator, all joined together via the linker L (claim 1). The chelating agent can be DOTA (e.g., claim 5). The structure for the ligand F in claims 13 and 22 – 46 matches the compounds of the instant claims. Claims 14 – 18 provide options for the linker. Therefore the claims of the instant application are not patentably distinguished over those of US’845.
The presence of a triazole ring is not claimed.
Pickens et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAC click chemistry to prepare the conjugates of US’845 that will result in a triazole ring being present in the final conjugate. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the AAC click chemistry reaction is taught by Pickens et al. as useful for the preparation of a variety of conjugates and is an efficient coupling reaction.
As to claim 28, the binding affinity of the conjugates or compounds in Jiaang et al. is not disclosed but aligns with the A portion of FAP-3000 whose binding affinity lies within the claimed range. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 10, 12, 14, 18, 21, 28 – 31, 47 and 108 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 15 of U.S. Patent No. 12,721,898 in view of Jiaang et al. (US 8,071,787) optionally further in view of Yang et al. (WO 2019/083990) or Pickens et el. (Bioconjugate chemistry, 2018). The claims of US’898 are drawn to compounds that bind to FAPα with a targeting moiety of formula (X) as defined in claim 1, linked to a linker L and Ia as defined in claim 1. The various L values in claims can include PEG segments.
The structure of the FAPα binding portion of the molecules claimed is not the same as those of the instant claims.
Jiaang et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to replace the Fa portion of the compound claimed with the molecules of Jiaang et al. that also bind to FAPα, rendering obvious the compounds of the instant claims. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because each of these moieties is known to bind to the same target but given the difference in structure, would exhibit slightly different behaviour such as binding affinity to FAPα and there is no evidence of record of unexpected results arising from the presently claimed FAPα binding portion of the molecule.
Chelators such as DOTA for the imaging agent portion of US’898 are not claimed.
Yang et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate optical or radiolabeled functional groups as taught by Yang et al. into the compounds of US’898 and Jiaang et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because various moieties including chelating agents can be coupled to FAP binding conjugates and will result in different imaging modalities or uses of the final compound. One of ordinary skill in the art can select from moieties known to be conjugated to FAP binding moieties depending on the desired use of the final compound.
The presence of a triazole ring is not claimed.
Pickens et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use the AAC click chemistry to prepare the conjugates of US’898 that will result in a triazole ring being present in the final conjugate. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the AAC click chemistry reaction is taught by Pickens et al. as useful for the preparation of a variety of conjugates and is an efficient coupling reaction.
As to claim 28, the binding affinity of the conjugates or compounds in Jiaang et al. is not disclosed but aligns with the A portion of FAP-3000 whose binding affinity lies within the claimed range. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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