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 .
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 04/23/2026 are acknowledged.
Previous Sequence Non-compliance is withdrawn in light of incorporation of SEQ ID NOs.
Applicants arguments with regard to “derivative” in 112(b) rejection is persuasive and accordingly, the rejection is withdrawn with regard to “derivative”.
In light of deleting “such as” in claims 12 and 23, previous 112(b) rejection for these claims is withdrawn.
However, applicants arguments for “18F”, “analogue” and “such as” are found not persuasive and so, the rejections are maintained. See the reasonings in Response to Arguments below.
In light of claim amendments, previous 103 rejection over Zhao is withdrawn.
However, applicants’ arguments for the previous 103 rejection over Velikyan are found not persuasive. Accordingly, the previous rejection is maintained.
Response to Arguments
With regard to 112(b) issues:
(i) In cited paragraph [0282] and Example 4, the 18F is complexed with Al, and the resulted complex, 18F-Al acts as nuclide, not 18F alone.
(ii) In the cited paragraph [0105] describes one of the species of the peptide, and it does not define the metes and bounds of analogue. In other words, claims says ‘a peptide analogue of SEQ ID NO:1 having at least 88.8% identity to SEQ ID NO:1. What is remaining 11.2% in the sequence?
(iii) the “such as” is not deleted from all places. Claims 14 and 24-25 still have “such as” in the claim language.
With regard to 103 rejection, applicants argue that Velikyan teaches radiochemistry and stability as dominant drivers of image quality and that SUV behavior is a consequence of chelator choice, radionuclide, stability, and pharmacokinetics. Velikyan does not analyze collagen-binding peptides at the level of protein-derived biological epitopes and does not teach that mimicking extracellular matrix (ECM) organizing proteins (as opposed to generic collagen binders) would improve SUV of the PET tracer.
Claims are drawn to a product (composion), which comprises compound of formula I and nuclide. The cited Velikyan also teaches structurally similar product, but silent on coupled peptide to the Gallium labeled-Chelator-Linker.
As explained in the rejection, there is a common property between two peptides, such as binding affinity towards collagen I. Though the peptide(s) can have different properties, but at least based on the binding affinity towards collagen I, linear peptide showed superior properties over the cyclic peptide. Therefore, a skilled person in the art would be motivated to replace cyclic peptide with a linear peptide.
Alternatively, molecular probe, Gallium labeled-Chelator -Linker is common in both cases. This probe can be coupled to any desirable peptide, since probe is like a fluorescent dye or a tracer, and so, based on its properties a skilled person in the art can extrapolate or explore to other possible peptides. There is a reasonable expectation of success of doing so, because such technology is well established in the art.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1-14 and 18-25 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 pre-AIA the applicant regards as the invention.
(i) Claims 1 and 8 recites 18F, which is a fluorine isotope for nuclide M. However, fluorine does not form a complex with the recited complexing agents. Specification also failed to define binding sites for fluorine isotope on the recited complexing agents or on linker or on peptide. So, it is not clear where fluorine isotope binds in the compound of formula (I). Accordingly, claim 1 and 8, and their dependents are rendered indefinite.
(ii) Claims 1 and 3 recites terms “analogue” for the recited peptide.
The terms “analogue” rendered its scope unclear, since it is not known to the skilled reader which structure are intended to be encompassed by this term. Such as term includes peptide from another peptide by a chemical reaction (including compounds/peptides which are structurally remote from the starting material), functional derivatives (such as compounds/peptides, wherein heteroatoms are exchanged by alternative atoms), compounds with numerous different types of side groups etc. However, there is no clear definition in the application to which extent the analogue might be modified while still being regarded as analogue. This has the effect that the person skilled in the art cannot decide clearly which compounds are to be covered by said claim and which are not.
Accordingly, claims 1 and 3, and their dependents are rendered indefinite.
(iii) claims 14 and 24-25 cite “such as” in the claim language. MPEP 2173.05(d) states that “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made. The examiner should analyze whether the metes and bounds of the claim are clearly set forth. Note that the mere use of the phrase "such as" or "for example" in a claim does not by itself render the claim indefinite”. Accordingly, claims 12, 14 and 23-25 are rendered indefinite.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-14 and 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Velikyan (Nuclear Medicine and Biology, 2014, 41, 728-736; see applicants filed IDS dated 12/16/2022) in view of Federico (Angew.Chem.Int.Ed., 2015, 54, 10980-10984; see applicants filed IDS dated 12/16/2022) and Simecek (ChemMedChem, 2013, 8, 95-103).
For claim 1:
Velikyan teaches a cyclic peptide c[CPGRVMHGLHLGDDEGPC] conjugated either to 2-(4,7-bis(2-(tert-butoxy)-2- oxoethyl)-1,4,7-triazonan-1-yl)acetic acid (NOTA(tBu)2) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triaza-cyclononan-1-yl)-5-(tert-butoxy)-5-oxopentanoic acid (NODAGA(tBu)3) via polyethylene glycol link (PEG2) was synthesized and labeled with 68Ga., wherein the cyclic peptide has micromolar affinity to collagen and excessive production of extracellular matrix macromolecules such as collagen I and III results in fibrotic tissue [see abstract and Introduction].
The above synthesized compounds can be represented by the following structures:
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, wherein Ga is 68Ga, which reads claimed nuclide [see Fig.1; section 3.1 for their preparative methods], wherein NO2A (NOTA) and NODAGA reads applicants complexing agents, wherein PEG2 is linker.
The above is interpreted as a composition comprising a compound of NOTA (or NODAGA)-Linker-Peptide and nuclide Gd.
Difference is that Velikyan silent on applicants SEQ ID NO:1 (LRELHLNNN).
The above deficiency can be cured by the teachings of Federico, which teaches LRELHLNNN, which is identical applicants SEQ ID NO:1 and it has nano molar affinity for collagen I [see Table 1]. So, a skilled person it the art would be motivated to replace large cyclic peptide in the teachings of Velikyn with a short peptide of Federico, in light of its high affinity for collagen and its size.
For claim 2:
In the conjugate in the teachings of Velikyn, see above under For claim 1, the ratio is equals to one.
For claim 3:
Velikyn teaches NOTA and NODAGA, which are nothing but applicants chelator in the formula Ib and If.
For claims 4-7:
As explained in For claim 1 above, the compound of Velikyn reads at least applicants claimed Cmpd 16.
For claim 8:
Velikyn silent on DOTA. However, based on teaching of Velikyn, it is obvious to extrapolate teachings of Velikyn to DOTA, as it is commercially established chelating agent like NOTA in the imaging, absent evidence to the contrary. Regardless, Simecek teaches that both DOTA and NOTA are most frequently utilized chelators in 68Ga radiopharmaceuticals [see Fig.1]. Accordingly, these are interpreted as equivalents. Case law holds that the mere substitution of an equivalent (something equal in value or meaning, as taught by analogous prior art) is not an act of invention; where equivalency is known to the prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958).
For claim 9:
Velikyn teaches their conjugate is dissolved in water and pH is adjusted [see section 2.3 Radiolabeling and in situ stability test]. Water can be a diluent or carrier or excipient.
For claim 10-14:
Velikyn also teaches their probes are useful for imaging and quantification of fibrosis [see title and abstract].
For claims 18:
Velikyn silent on DOTA. However, based on teaching of Velikyn, it is obvious to extrapolate teachings of Velikyn to DOTA, as it is commercially established chelating agent like NOTA in the imaging, absent evidence to the contrary. Regardless, Simecek teaches that both DOTA and NOTA are most frequently utilized chelators in 68Ga radiopharmaceuticals [see Fig.1]. Accordingly, these are interpreted as equivalents. Case law holds that the mere substitution of an equivalent (something equal in value or meaning, as taught by analogous prior art) is not an act of invention; where equivalency is known to the prior art, the substitution of one equivalent for another is not patentable. See In re Ruff 118 USPQ 343 (CCPA 1958).
For claim 19:
As explained in For claim 1 above, the compound of Velikyn reads at least applicants claimed Cmpd 16. The differences are addressed in For claim 1 above.
For claims 20-24:
Velikyn also teaches their probes are useful for imaging and quantification of fibrosis [see title and abstract].
For claim 25:
Velikyn teaches a method of diagnosis and monitoring fibrosis by administering Gd-NOTA (or NODAGA)-peptide probe [see Fig.4-8]. The differences in the peptide is explained under For claim 1 above.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components in the composition and their utility as probes diagnosing and monitoring fibrosis etc., were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed subject matter with a reasonable expectation of success.
Further, the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983). In the instant case, one is simply replace a large cyclic large peptide in the teachings of Velikyn with a short peptide from the teachings of Federico, in light of its advantages.
Conclusion
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 SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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