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 .
DETAILED ACTION
Claims 1, 3-5, 7-10 and 13 are pending in the application. Claims 1, 3-5, 7-10 and 13 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. PCT/US2018/026340 and Application Serial No. 17/016,189, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Regarding instant claims 5, 7-10 and 13, these claims each require a binding for human serum albumin in the range of about 0.25 to 50 micromolar and a specific affinity for a tumor associated molecular target in the range of about 0.1 to 0.75 nanomolar. These ranges first appear in (in the instant patent family) in Application Serial No. 16/134,789. These ranges, however, are only disclosed in conjunction with a particular ratio between them. For instance, the ‘789 application discloses the following on page 2:
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The various disclosures found in the ‘789 application contain the same limitation requiring the difference by a factor with a certain range, at least broadly 100 to about 10,000. Neither the ‘789 application nor any intervening applications disclose or suggest that this particular ratio can be omitted for embodiments otherwise disclosing specific albumin and tumor associated molecular target affinities.
For these reasons, the earliest effective filing date of claims 5, 7-10 and 13 is October 23rd, 2023 (the earliest the instant claims were presented in the application).
Regarding instant claims 1, 3 and 4, the same rationale applies relative to the disclosure of Application Serial No. 17/016,189 since there is no required value for relative affinity where the broadest disclosure appears in paragraph [0004] of the ‘189 application and requires a particular relative affinity for the multi-targeted compound as otherwise claimed. While Application Serial No. 17/016,189 incorporates PCT/US2018/026340 by reference, this application only broadly states the following in paragraph [0003]:
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The PCT application does not specifically disclose the instant limitation of “an active site that is distal to and sterically unimpeded by the albumin-binding domain and the therapeutic agent” and further does not describe (as opposed to only cytotoxin-containing and/or imaging agent-containing) a cytostatic therapeutic agent. A cytostatic therapeutic agent stops a tumor from growing but is not necessarily toxic and does not necessarily kill a tumor cell.
For these reasons, the earliest effective filing date of claims 1, 3 and 4 is October 23rd, 2023 (the earliest the instant claims were presented in the application).
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statement(s) filed on February 23rd, 2023, March 22nd, 2023, July 3rd, 2023, October 23rd, 2023, December 28th, 2023, June 6th, 2024, January 9th, 2025 and March 18th, 2025.
Claim Rejections - 35 USC § 112(a)
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.
(1 of 2) Claims 1, 3 and 4 are 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 new matter rejection.
Instant claim 1 was amended via preliminary amendment to delete a limitation regarding relative affinities between the first and second targeting domains. The instant application discloses the following broadest embodiment including the three domains defined by instant claim 1 on pages 1 and 2:
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The various disclosures found in the instant application contain the same limitation requiring the difference by a factor with a certain range, at least broadly 100 to about 10,000. The instant application as filed fails to disclose or suggest that this particular ratio can be omitted for embodiments otherwise disclosing specific albumin and tumor associated molecular target affinities.
While the instant application incorporates PCT/US2018/026340 by reference, this application only broadly states the following in paragraph [0003]:
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The PCT application does not specifically disclose the instant limitation of “an active site that is distal to and sterically unimpeded by the albumin-binding domain and the therapeutic agent” and further does not describe (as opposed to only cytotoxin-containing and/or imaging agent-containing) a cytostatic therapeutic agent. A cytostatic therapeutic agent stops a tumor from growing but is not necessarily toxic and does not necessarily kill a tumor cell. Even if the PCT application were considered valid support under 35 USC 112(a), 37 CFR 1.57(d) states:
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f).
In this situation, the broadest disclosure appears in a PCT application, not in a U.S. patent or U.S. patent application.
Accordingly, the instant claim 1 represents a genus that is broadened relative to both the actual original disclosure and the disclosures found in any parent applications with no guidance or direction.
Dependent claims 3 and 4 are rejected for the same reason as parent claim 1.
(2 of 2) Claims 5, 7-10 and 13 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 new matter rejection.
Instant claim 5 was amended via preliminary amendment to delete a limitation regarding relative affinities between the first and second targeting domains. These ranges, however, are only disclosed in the application as filed in conjunction with a particular ratio between them. For instance, the instant application discloses the following on page 2:
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The various disclosures found in the instant application contain the same limitation requiring the difference by a factor with a certain range, at least broadly 100 to about 10,000. The instant application as filed fails to disclose or suggest that this particular ratio can be omitted for embodiments otherwise disclosing specific albumin and tumor associated molecular target affinities.
Dependent claims 7-10 and 13 are rejected for the same reason as parent claim 5.
Claim Rejections - 35 USC § 112(b)
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 3 and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is rejected as indefinite since it depends from claim 2, which has been cancelled. For the purposes of examination, the Examiner has assumed that claim 3 was intended to depend from claim 1.
Claim 7 is rejected as indefinite since it depends from claim 6, which has been cancelled. For the purposes of examination, the Examiner has assumed that claim 7 was intended to depend from claim 5.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(1 of 2) Claim(s) 1, 3-5 and 7-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tien et al. Theranostics 2018, 8, 735-745, published January 1st, 2018.
Tian et al. teach the following on page 736:
To improve the pharmacokinetics of SSTR2 analogs and reduce PRRT toxicity, we conjugated a truncated Evans Blue (EB) molecule onto octreotate (EB-TATE). The EB moiety provided reversible binding of EB-TATE to albumin in vivo to extend the half-life in the blood. When the EB-TATE was slowly released into the tumor microenvironment, tumor uptake and internalization into SSTR positive cells resulted in delivery of radioactive particles and tumor cell killing. EB-TATE displayed significantly more favorable pharmacokinetics than TATE by achieving higher tumor to non-tumor contrast for both diagnostic positron emission tomography (PET) imaging with 86Y and radiotherapy using 90Y.
Tian et al. teach the following structure on page 740:
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The prior art refers to the structure above as EG-TATE and additionally teaches that the macrocycle (embraced by instant claim 10) in the bottom right corner was used to complex a radionuclide to yield 90Y-EB-TATE (page 40, right column). Tian et al. further teach that the bottom-left portion binds albumin as follows on page 736: “To improve the pharmacokinetics of SSTR2 analogs and reduce PRRT toxicity, we conjugated a truncated Evans Blue (EB) molecule onto octreotate (EB-TATE). The EB moiety provided reversible binding of EB-TATE to albumin in vivo to extend the half-life in the blood.” Tian et al. teach that the top portion targets SSTR2 as follows on page 736: “The most frequently used somatostatin analogs in PRRT clinical practice are octreotide and octreotate (TATE); the latter one has higher affinity and selectivity towards SSTR2.” Accordingly, the prior art teaches the three required domains of claims 1 and 5. Tian et al. teach on page 739 (left column):
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The albumin affinity of 4.8 µM is embraced by the range of claim 5. Regarding binding to SSTR2, Tian et al. teach Figure 2B where % of maximum binding occurs at about -8 corresponding to a concentration of about 10 nm, which falls within the range of claim 5 (and relative to instant claims 3 and 7, with an exemplary range of moderate to high affinity disclosed on page 3 of the instant specification). The prior art contains a chelating agent or a polyaza polycarboxylic macrocycle as recited in instant claim 9.
Regarding instant claims 4, 8 and 10 that embrace beta-emitting radionuclides, the prior art teaches conjugation to 90Y where Tian et al. teach on page 736: “90Y is a pure beta-emitter with a half-life of 64.1 hours, maximum energy of 2.28 MeV, and penetration range of 11 mm.”
(2 of 2) Claim(s) 1, 3-5, 7-10 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rousseau et al. Nuclear Medicine and Biology 2018, 66, 10-17, which was published August 9th, 2018.
Rousseau et al. teach the following structures on page 13:
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The legend for Figure 1 teaches the top left portions bind albumin (and corresponds to a substituted 4-(4-iodophenyl)butanoic acid (or 4-iodophenylalkanoic acid) recited instant claim 13). The conjugates above further contain octreotate and where the prior art demonstrates binding to SSTR2 on pages 13 and 14 as follows:
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Both affinities for SSTR2 are embraced by the range of instant claim 5 (and relative to instant claims 3 and 7, within an exemplary range of moderate to high affinity disclosed on page 3 of the instant specification). Regarding instant claims 4, 8 and 10, the prior art teaches complexation with 177Lu (title), which is a beta-emitting radionuclide as disclosed in paragraph [0088] of the instant specification. The prior art contains a chelating agent or a polyaza polycarboxylic macrocycle as recited in instant claim 9. Accordingly, the prior art teaches the three components of instant claims 1 and 5 along with structures that further correspond to instant claims 3, 4, 7-10 and 13. The prior art does not teach a specific affinity for human serum albumin; however, the prior art teaches the presence of a structure explicitly recited in instant claim 13. MPEP 2112.01(II) states: “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW P COUGHLIN whose telephone number is (571)270-1311. The examiner can normally be reached Monday - Friday, 10 am - 6 pm EST.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626