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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 3/25/2025 wherein claims 8-11 were amended. In addition, the Examiner acknowledges receipt of the amendment filed 8/11/2024.
Note(s): Claims 1-17 are pending.
Priority
This application is a CON of 15/739,234 filed 12/22/2017 (now abandoned) and 15/739,234 is a 371 of PCT/IB2016/001089 filed 6/24/2016 and PCT/IB2016/001089 claims benefit to PRO of 62176901 filed 6/25/2015.
Note(s): The earliest effective filing date is 6/25/2015 as the pending invention is fully supported therein.
Claim Interpretation
Independent claim 1 is directed to a method of treating a patient that has a cancer that over-expresses somatostatin receptors comprising administering to said patient a combination of a Peptide Receptor Radionuclide therapy (PRRT) and an Immuno-oncology therapy, wherein the combined effect of the PRRT and the Immuno-oncology therapy, produces a therapeutic effect on said cancer.
Independent claim 2 is directed to a method of treating a patient that has a cancer that over-expresses somatostatin receptors comprising administering to said patient a combination of a Peptide Receptor Radionuclide therapy (PRRT) and an inhibitor that inhibits the PD-1/PD-L 1/CTLA-4 pathway, wherein the combined effect of the PRRT and the inhibitor of PD-1IPD-L 1 pathway produces a therapeutic effect on said cancer.
Applicant’s Election
Applicant's election without traverse of Group II (pending claims 2-17) filed 8/11/2024 and 3/25/2025 is acknowledged. Hence, the restriction requirement is still deemed proper and is therefore made FINAL.
In the responses filed 8/11/2024 and 3/25/2025 Applicant elected the species wherein the PPRT agent is 177Lu-DOTA-[O]-Tyr3-octreotate; inhibitor is MPDL3280A; cancer of interest is small cell lung cancer (SCLC); therapeutic effect of interest is the growth of a neuroendocrine tumor; and the pathway is PD-L1. In the response filed 3/25/2025, Applicant also stated that the cancer is not responsive to Sandostatin or Somatuline and the neuroendocrine tumor is a non-functional tumor. Claims 2-15 and 17 read on the elected species.
Initially, Applicant’s elected species was searched. Prior art was found to render the elected species obvious. Thus, the search was not further extended.
Note(s): The bold text indicates the components of the elected species.
Withdrawn Claims
Claims 1 and 16 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statement
The information disclosure statement filed 4/21/2022, 2/5/2024, and 5/13/2024 were considered.
Written Description Rejection
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.
Claims 2-15 and 17 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection.
(I) The pending application does not sufficiently describe the invention as it relates to PD-1/PD-L1/CTLA-4 inhibitors other than Nivolumab, MK-3475, MPDL3280A, MED14736, ipilimumab, and tremelimumab that may treat a somatostatin related cancer in combination with PRRT (see independent claim 20.
(II) The pending application does not sufficiently describe the invention as it relates to antibodies that inhibit the PD-1/PD-L1/CTLA-4 pathway other than Nivolumab, MK-3475, MPDL3280A, MED14736, ipilimumab, and tremelimumab (see claims 4 and 5).
(II) The pending application does not sufficiently describe the invention as it relates to somatostatin related cancers that are treatable with a combination of PRRT and a PD-1/PD-L1/CTLA-4 inhibitor other than those in claims 9 and 10).
(IV) The pending application does not sufficiently describe the invention as it relates to PRRT agents that may be used in combination with PD-1/PD-L1/CTLA-4 inhibitors other than 177Lu-DOT[O]-Tyr3-octreotate, 111In-DTPA-octreotide, 90Y-DOTATOC, 90Y-DOTATE, 90-Y-Lanreotide, 177-DOTACIN, 111In-DOTA-BASS, and 177Lu-DOTA-JR11.
Furthermore, as illustrated in claim 14, “The method of claim 12, wherein said cancer is not responsive to Sandostatin (Novartis) or Somatuline® (Ipsen).”, not all somatostatin related cancers are responsive to all somatostatin related PRRT agents, not all cancers are treatable with the PRRT-inhibitor of PD-1/PD-L1/CTLA-4 combination. As a result, the invention clearly illustrates that not all substances are compatible with the pending invention.
Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
Prevention Claims
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.
Claims 2-15 and 17 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection.
The instant application does not sufficiently describe the invention as it relates to preventing (inhibiting) the PD-1/PD-L1/CTLA-4 pathway such that a subject is effectively treated for cancer (see independent claim 2). In addition, the application does not sufficiently describe as it relates to the inhibition of growth of a neuroendocrine tumor, inhibition or proliferation of neuroendocrine tumor cells, and inhibition of neuroendocrine tumor metastases (see claim 8). According to the Merriam-Webster’s Dictionary, the term ‘inhibit’ is defined as ‘to hinder, restrain, or prevent and action or process’. Based on the disclosure, the application lacks evidence that by administering any and all PRRT agents in combination with any and all inhibitors of the PD-1/PD-L1/CTLA-4 pathway, the treatment of cancer results in the inhibition of cancer in a subject. It should be noted that Applicant’s definition of ‘treatment’ includes treating (reduction of cancer) as well as prevention (inhibition) of cancer. However, no evidence is provided to indicated that over one’s lifetime, a subject administered the PRRT agent in combination with a PD-1/PD-L1/CTLA-4 pathway inhibitor never develop or experience symptoms associated or related to cancer.
For the reasons set forth above, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
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 2-15 and 17 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.
Claims 2-15 and 17: Independent claim 2 is ambiguous because one cannot determine the metes and bounds of the claim. (1) according to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under, in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed to any cancer that overexpresses somatostatin receptors that may be treated by administering any peptide receptor radionuclide therapy (PRRT) agent in combination with any inhibitor of the PD-1/PD-L1/CTLA-4 pathway. As a result, pending claim 2 encompasses a massive number of distinct members such that one skilled in the art cannot determine the metes and bounds of the claim. Thus, due to an inability to envision all of the PRRT agents and inhibitors and combinations thereof defined by the Markush groups, the claim is deemed to be vague and indefinite.
(2) As indicated by claim 14, “The method of claim 12, wherein said cancer is not responsive to Sandostatin (Novartis) or Somatuline® (Ipsen).”, not all somatostatin related cancers are responsive to all somatostatin related PRRT agents. As a result, the invention illustrates that not all substances that bind somatostatin receptors and may be used for PRRT are compatible with the pending invention. As a result, one cannot readily determine, the metes and bounds of the invention to clearly state which somatostatin binding agents useful for PRRT may be used independently of and in combination with an inhibitor of the PD-1/PD-L1/CTLA-4 pathway.
Since claims 3-15 and 17 depend upon independent claim 2 for clarity, those claims are also vague and indefinite.
Claim 8: It is unclear what conditions/limitation are being placed on the term ‘inhibiting’ and ‘reduce’ and whether or not Applicant is using the terms interchangeably. In particular, The terms “inhibition” and “reducing” in lines 2-5 are relative terms which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 14: According to MPEP 2173.05(u) regarding trademarks/trade names in a claim, a trademark/trade name is used to identify a source of goods, not the name of the goods themselves. Thus, the trademark/trade name does not define or describe the goods associated with the trademark/trade name (see definitions of trademark and trade name in MPEP 608.01(v)).
In claim 14, the trademark/trade name is used as a limitation to identify or describe a particular material/product and as such renders the claim ambiguous. The claim scope is uncertain since the trademark/trade name cannot be used properly to describe any particular material or product. In fact, the value of a trademark would be lost to the extent that it became the generic name of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark/trade name in a claim to describe a material or product not only renders the claim indefinite, but also constitutes an improper use of the trademark/trade name (see MPEP 2173.05(u)).
Claim 15: The phrase “low response” in lines 1-2 is a relative term which renders the claim indefinite. The phrase “low response” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
103 Rejection
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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 2-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Esser et al (Eur. J. Nucl. Med. Mol. Imaging, 2006, Vol. 33, No. 11, pages 1346-1351) in view of Sunshine et al (Current Opinion in Pharmacology, available online June 2, 2015, Vol. 23, pages 32-38).
Independent claim 2 is directed to a method of treating a patient that has a cancer that over-expresses somatostatin receptors comprising administering to said patient a combination of a Peptide Receptor Radionuclide therapy (PRRT) and an inhibitor that inhibits the PD-1/PD-L 1/CTLA-4 pathway, wherein the combined effect of the PRRT and the inhibitor of PD-1IPD-L 1 pathway produces a therapeutic effect on said cancer.
Claim 3 is directed the PRRT agent [177]Lutetium-DOTA0-Tyr3-octreotate.
Claim 4 is directed to antibody inhibitors of the PD1/PD-L1/CTLA-4 pathway.
Claim 5 is directed to antibody inhibitors that target the PD1 pathway.
Claim 6 is directed to inhibitors selected from Nivolumab, MK-3475, MPDL3280A, MED14736, ipilimumab, and tremelimumab.
Claim 7 is direct to neuroendocrine tumors.
Claim 8 is directed to inhibiting the growth of a neuroendocrine tumor, inhibiting proliferation of neuroendocrine tumor cells, inhibiting neuroendocrine tumor metastases, inducing neuroendocrine tumor cell differentiation, reducing tumorgenicity of neuroendocrine tumor cells and methods of reducing the frequency of cancer stem cells, and/or tumor initiating cells in a neuroendocrine tumor.
Claims 9 and 10 are is directed to various neuroendocrine tumors set forth therein.
Claim 12 is directed to small cell lung cancer.
Claim 13 is directed to progressive midgut neuroendocrine tumor.
Esser et al disclose that it is well known in the art to use 177Lu-DOTA0-Tyr3-octretotate (177Lu-DOTATATE) for PRRT in the treatment of neuroendocrine tumors/cancers (see entire document, especially, abstract; page 1347, left column , lines 10-23; page 1347, right column, ‘Radiopharmaceuticals’, ‘Infusion’; page 1348, Figure 1). On page 1347, lines14 and 21, respectively, it is disclose that 177Lu-DOTATATE may be used for midgut carcinoid and small cell lung cancer evaluation.
In Table 1 (page 1349), the residence time for DOTATE is disclosed in the various patient tumors. In Figure 3 (page 1350), whole body scans are disclosed to illustrate post therapy results after 177Lu-DOTATATE administration. Esser et al concluded that 177Lu-DOTATATE is a preferred peptide for PRRT (pages 1349-1350, bridging paragraph).
Sunshine et al disclose that it is well known in the art to use PD-1/PD-L 1 pathway antibody inhibitors such as Nivolumab, pembrolizumab, MPDL3280A, MEDI4736, and BMS-936559 for treating melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin lymphoma, amongst other types of tumors (see entire document, especially, abstract; page 32, right column, first complete paragraph; pages 32-33, bridging paragraph). Figure 1 (page 35) discloses the association of PD-L1 expression in pre-treatment tumor specimens with responses to PD-1/PD-L 1 pathway antibody inhibitors.
Table 1 (page 33) is directed to biological agents that target PD1 and PD-L1. Those biological agents include AMP-224, AP-514 (MED10680), Nivolumab, pidilizumab, Pembrolizumab (MK-3475), BMS-936559 (MDX1105), MED14736, MPDL3280A, and MSB0010718C.
Table 2 (page 33) discloses cancers/tumors that may be targeted by the PD1 and PD-L1 pathway. Those cancers/tumors include melanoma, NSCLC, RCC, bladder, prostate, Hodgkin lymphoma, ovarian, breast, CRC, gastric, and SCCHN. The table discloses data for various PD-1/PD-L 1 pathway antibody inhibitors.
Claim 11 is directed to low, medium, and high grade neuroendocrine tumors.
Both Esser et al and Sunshine et al disclose neuroendocrine tumors/cancers in general (see discussion supra). Thus, it would have been obvious to the skilled artisan that all grades of tumors are encompassed therein.
Claim 14 is directed to the cancer not being responsive to Sandostatin or Somatuline.
While neither Esser et al and Sunshine et al disclose that their cancers/tumors of interest are not responsive to Sandostatin or Somatuline, it would be obvious to the skilled artisan that the tumors/cancers disclosed therein are neuroendocrine tumors/cancers that overlap with those of the pending invention. According to MPEP 2112.01, if the products of identical chemical composition cannot have mutually exclusive properties. Thus, if the composition of the pending invention is not responsive to Sandostatin or Somatuline, then the prior art composition would inherently possess the same property.
Claim 15 is directed to the cancer not being responsive to or having a low response to a PD1/PD-L1 pathway inhibitor.
While neither Esser et al and Sunshine et al disclose that their cancers/tumors of interest are not responsive or have low response to a PD1/PD-L1 pathway inhibitor, it would be obvious to the skilled artisan that the tumors/cancers disclosed therein are neuroendocrine tumors/cancers that overlap with those of the pending invention. According to MPEP 2112.01, if the products of identical chemical composition cannot have mutually exclusive properties. Thus, if the composition of the pending invention is not responsive or has a low response to a PD1/PD-L1 pathway inhibitor, then the prior art composition would inherently possess the same property.
Claim 17 is directed to a non-functional neuroendocrine tumor.
While neither Esser et al and Sunshine et al disclose that their cancers/tumors of interest are non-functional neuroendocrine tumors/cancers, it would be obvious to the skilled artisan that the tumors/cancers disclosed therein are neuroendocrine tumors/cancers that overlap with those of the pending invention. According to MPEP 2112.01, if the products of identical chemical composition cannot have mutually exclusive properties. Thus, if the composition of the pending invention is are non-functional neuroendocrine tumors/cancers, then the prior art composition would inherently possess the same property.
Furthermore, it would have been obvious to one of ordinary skill in the art prior to the effective date of the pending invention to combine the teachings of Esser et al and Sunshine et al for the following reasons. (1) Esser et al disclose that it is well known in the art to use 177Lu-DOTATATE for evaluating neuroendocrine tumors. (2) Sunshine et al disclose that it is well known in the art to use various PD-1/PD-L 1 pathway inhibitors as described supra for evaluating a variety of tumors/cancers. (3) According to MPEP 2144.06, it is prime facie obvious to combine two substances each of which is taught in the prior art to be useful for the same purpose, in order to form a third substance (composition) to be used for the very same purpose. The ideal of forming the compositions that are used for the same purpose by combining the substances flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Hence, for the reasons herein, it would have been obvious to combine Esser et al and Sunshine et al and render obvious claims 2-15 and 17 as explained supra.
Since both Esser et al and Sunshine et al are directed to treatment of overlapping cancers/tumors, the references may be considered to be within the same field of endeavor. Thus, the reference teachings are combinable.
Comments/Notes
It should be noted that the full scope of Group II was not searched.
Conclusion
Claims 2-15 and 17 are rejected and claims 1 and 16 are withdrawn.
Future Correspondences
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
February 27, 2026