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
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-2, 13, 16, 22, 24, 28-32 and species: CCR2 inhibitor, additional cancer therapy, chemotherapy, FOLFIRINOX, additional cancer therapy administered substantially simultaneous, FOLFIRINOX, previous treatment administered before the chemokine receptor inhibitor in the reply filed 03/02/2026 is acknowledged.
Claims 6, 10, 20, 27, 36 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 03/02/2026.
Claims 1-2, 4-5, 13, 16, 19, 22-24, 28-32 are now under consideration in the instant Office Action.
Claim Rejections - 35 USC § 112
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 1-2, 5, 13, 16, 19, 22-24, 28, 30, and 32 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.
See MPEP §2163(I)(A) which states: "The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
Claim 1 calls for a 41BB agonist, a LAG3 antagonist, and any chemokine receptor inhibitor with a functional requirement for treating pancreatic ductal adenocarcinoma in a subject. There is no specific structural requirement for the 41BB agonist, a LAG3 antagonist, and any chemokine receptor inhibitor beyond the required function. The instant claims call for protein structures based on their functional activities, such as serving as an agonist, antagonist, or receptor inhibitor without providing any structural detail as to what genus of molecules they belong to. The required function of the proteins in treating PDAC can be achieved in any form, no specific structure is required, as long as they can bind to their claimed receptor and treating PDAC. The scope of the claim is so broad and reads on so many possible genera that it is clear that the specification fails to describe all of the possible means of achieving the response linked to its function. The claims do not require any particular structure for the proteins and inhibitors or that they possess any particular conserved structure or other disclosed distinguishing features. Therefore, the genera are merely defined by function and the instant specification fails to describe the full genera of the possible methods that are encompassed by these claims.
There is no structural requirement for the claimed 41BB agonist, a LAG3 antagonist, and CCR2 chemokine receptor inhibitor beyond function. The claimed activity of the proteins and inhibitors can be achieved in any form as long as they provide the specifically claimed function. Further, compounded by the limitation of treating PDAC, it is unclear what structures would meet the requirements to achieve this function and also be considered in the disclosure by Applicant. It is noted that the dependent claims 4, 29, and 31 do recite particular species for the 41BB agonist, LAG3 antagonist, and CCR2 chemokine receptor inhibitors; however, the remainder of the claims fail to provide sufficient structural details for the proteins nor do they recite the specific combination of species within the larger genera that are to be used in the combination therapy.
There are a few specific examples of 41BB agonists, a LAG3 antagonists, and chemokine receptor inhibitors in the instant specification and dependent claims, but there is no support provided that the Applicant have envisioned all of the possible variants encompasses by these functional requirements of the instant claims. Further, the instant claims do not require that the claimed proteins and inhibitors possess any particular conserved structure or other disclosed distinguishing feature. The scope of the terms of the “agonist”, “antagonist”, and “chemokine receptor inhibitor” is so broad and reads on so many possible genera and the instant specification fails to describe any of the possible proteins that are encompassed by this term. The “agonist”, “antagonist”, and “chemokine receptor inhibitor” terminologies encompasses any agent that has the required function but the instant specification fails to teach all the possible agents encompassed by the possible agents in the instant claim. The claims do not require that the “agonists”, “antagonists”, and “chemokine receptor inhibitors” possess any particular conserved structure or other disclosed distinguishing feature. The terminologies encompasses many things including antibodies, proteins, peptides, hormones, small drugs or other drugs as long as they achieve the required function. Thus the claims are drawn to multiple genera of molecules that are defined only by they function as a chemotherapeutic agent. Therefore, the genus is merely defined by function and the instant specification fails to describe the full genus of molecules that are encompassed by this claim.
To provide adequate written description and evidence of possession of claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of prospective activity or function. There is not even identification of any particular portion of the structure that must be conserved for said activity except its function. The specification does not provide a complete structure of all possible forms of the claimed proteins and inhibitors, and fails to provide a representative number of species for any genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genera of 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed structure of the encompassed agents, fragments and variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claims 1-2, 5, 13, 16, 19, 22-24, 28, 30, and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating PDAC using LOB12.3 and C9B7W and RS504393, does not reasonably provide enablement for treating PDAC with any species in the genera of 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include but are not limited to:
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The breadth of the claims;
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The nature of the invention;
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The state of the prior art;
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The level of one of ordinary skill;
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The level of predictability in the art;
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The amount of direction provided by the inventor;
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The existence of working examples; and
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The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors most relevant to this rejection are 1) amount of direction provided by the inventor, 2) the quantity of experimentation needed to make or use the invention based on the content of the disclosure, and 3) the existence of working examples. In the instant case, the amount of direction provided by the inventor, the quantity of experimentation needed to make or use the invention disclosed in the specification, and the existence of working examples, as filed, would not be sufficient to enable the skilled artisan to make and/or use the claimed invention at the time the application was filed without undue experimentation.
The amount of direction provided by the inventor - Due to the high level of unpredictability in the area of treating PDAC, the skilled artisan would need significant guidance in preparing a combination therapy containing 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors that fits the broad claim limitations provided by the Applicant. The instant application recites a wide genus of agonists, antagonists, and inhibitors ranging from small molecules to large antibodies. This language includes an immense number of molecules that include any structure able to perform the claimed activity. There is little guidance provided by the Applicant on how to make and use the broad range of 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors that are able to bind to the claimed protein encompassed by the claim, let alone treat PDAC as outlined by the claims. Considering this, one of ordinary skill in the art has no way of knowing which molecules will be able to result in the desired activity as claimed, let alone in combination with the other therapies recited in the claims. Given the current state of the art, the Applicant is not enabled to make and use the claimed combination therapy comprising 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors that do not have a defined structure for each species.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure – As discussed above, the instant claims have been found to require a high specificity of identity in order to bind to the claimed target and result in the desired activity. Given the high degree of specificity required to achieve the desired results of the invention, it would require undue experimentation to practice this invention while needing to ascertain which of the individual species of 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors, which do not explicitly recite a structure in the instant claims, would result in treating PDAC, let alone discover which combinations of therapies from the large number of unknown species would be able to work in tandem to achieve the desired outcome.
The existence of working examples – As stated above, instant claims 4, 29, and 31 and the instant specification reasonably provide enablement for the combination therapy comprising the anti-41BB agonist LOB12.3, the anti-LAG3 antagonist C9B7W, and the chemokine receptor inhibitor RS504393 that may be used to treat PDAC; however, there is no showing in the specification of any means by which one skilled in the art could prepare any combination of any species in the broad genera of 41BB agonists, LAG3 antagonists, and chemokine receptor inhibitors that would be able to treat PDAC effectively as claimed.
In conclusion upon careful consideration of the Wands factors that are used to determine whether undue experimentation is required to practice an invention, the amount of direction provided by the inventor, and the working examples provided, as filed, is not deemed sufficient to enable the skilled artisan to make and/or use the invention commensurate in scope with the instant claims at the time the application was filed without undue experimentation.
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.
Claims 1-2, 4-5, 13, 16, 19, 22-24, and 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Elstar Therapeutics Inc. (WO 2020/069372, in IDS filed 07/27/2023, hereinafter "Elstar"), in view of Zheng et al. (WO 2014/144,666 A1, in IDS filed 07/27/2023), and Zebala et al. (US 10,660,909 B2, in IDS filed 07/27/2023).
Elstar discloses a method for treating a subject for pancreatic ductal adenocarcinoma (PDAC), see pg. 72, lines 3-9; pg. 211, lines 13-15. Elstar teaches the use of a 4-1BB agonist as an immune cell engager, a LAG3 antagonist, and a chemokine receptor inhibitor, see pg. 30, lines 16-17, and the use of an additional checkpoint inhibitor wherein "the methods further comprise administering a second therapeutic treatment, the therapeutic agent is a checkpoint inhibitor", see pg. 72, lines 13-14, 17, wherein the "check point inhibitor is... an anti-LAG3 antibody", see pg. 72, lines 18-20. Elstar also teaches that "the invention provides an isolated multispecific, e.g., a bispecific, molecule, comprising: a first binding moiety that reduces recruitment of inflammatory monocytes to tumor, optionally wherein the first binding moiety binds to and/or inhibits CCR2" (see pg. 29, lines 28-31). Elstar also teaches that an additional chemokine receptor inhibitor can be administered to treat PDAC, see pg. 2, lines 23-24. This meets the limitations of instant claims 1 and 2 wherein a combination therapy of 41BB agonists, a LAG3 antagonist, and a chemokine receptor inhibitor is administered to treat PDAC, instant claim 5 wherein an additional chemokine receptor inhibitor is administered, and instant claim 32 wherein the combination therapy can be administered simultaneously.
However, Elstar is silent on the species of 41BB agonists and LAG3 antagonists and previous treatment plans. Zheng et al. remedies this deficiency.
Zheng et al. teaches various methods of administering cancer immunotherapies, see paragraph 0003. Zheng et al. teaches a monoclonal anti-LAG3 antibody, which is known as “C9B7W” and is a humanized or fully human antibody comprising the CDRs of the instantly claimed C9B7W, see paragraph 00245. Zheng et al. teaches a monoclonal antibody that binds 4-1BB, wherein the anti-4-1BB antibody is monoclonal antibody clone LOB 12.3, see paragraph 0029. This meets the limitations of instant claim 28 and 29 wherein the 41BB agonist is an anti-41BB antibody known as LOB12.3, and instant claims 30 and 31 wherein the LAG3 antagonist is an antibody known as C9B7W.
Additionally, Zheng et al. teaches previous chemotherapeutic treatments and combination therapies with the target of treating cancer. Zheng et al. discloses the administration of “FOLFIRINOX” in combination with other traditional therapies or immunotherapies, see paragraphs 00251-00252. Zheng et al. also discloses that a therapy can be “used in conjunction with anticancer treatment. Alternatively, the therapy may precede or follow the other agent treatment by intervals ranging from minutes to weeks”, see paragraph 00254. This meets the limitations of instant claim 13 wherein an additional cancer therapy was previously administered, instant claim 16 wherein the additional cancer therapy is FOLFIRNIOX, instant claim 19 wherein the additional cancer therapy is administered prior to the combination therapy, instant claim 22-24 wherein the subject had been previously treated for PDAC and was deemed resistant, and instant claim 32 wherein the combination therapy can be administered simultaneously.
However, Elstar and Zheng et al. do not teach the identity of the CCR2 chemokine receptor inhibitor. Zebala et al. remedies this deficiency.
Zebala et al. teaches a composition which administers an antagonist of CCR2 and additional agents that may be in the form of a single composition, see column 4, lines 60-63, wherein the “method comprises administering to said patient a therapeutically effective amount of at least one compound of formula I... or pharmaceutical compositions thereof, in combination another anticancer therapy comprising: (a) a 4-1BB agonist (immunotherapy may alternatively consist of an antibody that binds to an agonist of a protein selected from the group consisting of. 4-1BB. CD137, (column 25, lines 64-67; the immunotherapy is a CD137 4-1BB agonist, such as an agonistic CD137 …. (b) a LAG3 antagonist (the immunotherapy is a LAG-3 antagonist, such as an antagonistic LAG-3 antibody, column 36, lines 39-40) (c) a CCR2 inhibitor (agents for combination therapies include agents that inhibit or deplete macrophages or monocytes, column 35, lines 46-47; … suitable CCR2 antagonists include, for example, CCX140-B, CCX872, CCX915, MLN1202, JNJ-17166864, JNJ-27141491, MK-0812, PF-04136309, PF-04634817, BMS-741672, 1NCB8696, INCB3284, INCB3344, NIBR-1282, NIBR-177, GSK-1344386B, CCR2-RA-R, RS504393, column 35, lines. 66-67 and column 36, lines 1-3”. This meets the limitations of instant claim 4 wherein the chemokine receptor inhibitor is RS504393.
It would have been obvious to one of ordinary skill in the art at the time of the invention to use method for treating PDAC taught by Elstar, which comprises using a 41BB agonist, LAG3 antagonist, and CCR2 chemokine receptor inhibitors, with the teachings of Zheng et al. which disclose the identities of the 41BB agonists and LAG3 agonists, as well as considerations of previous treatment plans using FOLFIRINOX that the PDAC was resistant to. One of ordinary skill in the art would be motivated to utilize the teachings of Zebala, which disclose the same combination of 41BB agonist, LAG3 antagonist, and species of CCR2 chemokine receptor inhibitor in a combinatory therapy to treat cancer. Given that each of the references discloses a method to treat cancer using combination therapies that are well known in the art to slow or inhibitor tumor growth, one would be motivated to combine the teachings with the expectation of treating PDAC in a subject as it would target previous deficiencies and intercede on critical pathways in the development of the cancer.
Therefore, claims 1-2, 4-5, 13, 16, 19, 22-24, and 28-32 are rejected as obvious over Elstar, Zheng et al., and Zebala et al.
Conclusion
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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