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 .
Claim Status
Applicant’s amendment filed March 10, 2025 has been received and entered.
Claims 1, 4-6, 8-11, 16, 21-22, 24, and 26 have been amended.
Claims 2-3, 7, 12-15, 18-20, 23, 25, and 27-36 have been canceled.
Claims 1, 4-6, 8-11, 16-17, 21-22, 24, and 26 are pending and under consideration.
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. This application is a 371 of PCT/CN2022/101000 filed June 24, 2022, which is a continuation of PCT/CN2022/092803 filed May 13,2022, which is a continuation of PCT/CN2021/102324 filed June 25, 2021.
However, Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) 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 PCT/CN2021/102324 filed June 25, 2021, fails 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.
Claims 5-6 are drawn to the amino acid sequences (SEQ ID NOs) of the anti-CCR8 antibody heavy chain variable region comprising SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, 87, 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 and the light chain variable region comprising SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, 89, 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111.
Prior application PCT/CN2021/102324 only discloses SEQ ID NOs: 1-89. The first occurrence of all the sequences recited in claims 5-6 is PCT/CN2022/092803 filed May 13,2022. Therefore, claims 5-6 of the instant application are not entitled to the benefit of the prior application date of June 25, 2021.
Should Applicant disagree with the examiner’s factual determination as to the disclosure of the various sequences, Applicant may point out the particular places within application PCT/CN2021/102324 which discloses those sequences.
Accordingly, the PCT/CN2022/092803 filing date of May 13, 2022 will be used for the purpose of applying art for claims 5-6. The PCT/CN2021/102324 filing date of June 25, 2021 will be used for the purpose of applying art for claims 1, 4, 8-11, 16-17, 21-22, 24, and 26.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 20, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 10-11, 16-17, 21, and 26 are objected to because of the following informalities:
Claim 1 - should read “A monoclonal antibody…”.
Claims 10-11 - should read “a CCR8 specific antibody…”.
Claim 16 - should read “An isolated nucleic acid molecule encoding the monoclonal antibody or antigen-binding fragment of claim 1”.
Claim 21 (i) - should read “the monoclonal antibody or an antigen-binding fragment thereof of claim 1…”.
Claim 26(i) - should read “wherein the cancer is breast cancer, gastric cancer, ovarian cancer, , liver cancer, colon cancer, or pancreatic cancer,[[;]] the neuropathic pain is induced by diabetes or spinal cord injury, and the IgG4-related disease is IgG4-related sclerosing cholangitis”. Note, pancreatic cancer is listed twice.
Appropriate correction is required.
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.
Claims 21 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 21 recites an antibody conjugate which comprises (i) the monoclonal antibody or antigen-binding fragment of claim 1, or a combination thereof. It is unclear what “the combination thereof” is referring. Is the antibody conjugate comprised of both the antibody and antibody fragments thereof? For the purpose of examination the claim is being interpreted as an antibody conjugate comprising the antibody or an antibody fragment thereof, and not a combination of both.
Claim 21(ii) recites the limitation “a coupling moiety coupled to the antibody moiety”. There is insufficient antecedent basis for an antibody moiety in the claim.
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.
WRITTEN DESCRIPTION #1
Claim 6 is rejected under 35 U.S.C. 112(a), 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, at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See MPEP § 2163.
Claim 6 is drawn to the anti-CCR8 antibody of claim 1 comprising a heavy chain variable region with a sequence that is at least 85% identical to SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, 87, 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 or a light chain variable region with a sequence that is at least 85% identical to SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, 89, 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111.
The claim encompasses a large genus of structurally distinct polypeptides allowing for up to 15% variability in the recited 26 heavy chain variable region amino acid sequences and/or the 28 light chain variable region amino acid sequences. However, neither the claims nor the specification disclose how the sequences may vary (i.e., insertion, deletion, substitution) or where in the sequence such variation may occur. Therefore, it can be considered that the inventions defined by claim 6 encompass countless possible substitutions. Combinations of single or double substitutions further multiply the possibilities.
The recited heavy chain variable sequences range from 112 to 124 amino acids in length, with the majority being 123 amino acids, while the recited light chain variable domain amino acid sequences are all 112 amino acids. When considering only substitutions, a polypeptide that is 85% identical to a sequence of 123 amino acids would allow for up to 19 amino acid substitutions, while a sequence comprising 112 amino acids would allow for up to 17 amino acid substitutions.
However, the instant specification only demonstrates the results for 16 anti-CCR8 clones. Further, none of the 16 disclosed anti-CCR8 antibodies comprise a heavy chain variable region with an amino acid sequence of SEQ ID NO: 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 or a light chain variable region with an amino acid sequence of SEQ ID NO: 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111.
It is well understood in the art that protein folding and formulation are complex and fairly unpredictable processes, in such that substituting even one amino acid within the sequence can change the structure and function of said protein. For example, Teng et al. teach that amino acid substitutions located at the binding interface or active site cleft could block the entrance to the active site , change the recognition, alter the specificity, or affect the binding affinity of the antibody [Introduction]. Furthermore, Teng teaches amino acid substitutions at the interaction interface may result in binding affinity changes, and thus affect the structure of the protein complex [Section 3.1].
The instant specification discloses that the 16 antibodies bind to human CCR8, however, their EC50 values range from 0.195 nM to 20.56 nM [0175, Table 3]. Thus, one cannot readily extrapolate the properties of an antibody comprising a heavy chain variable region represented by SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, or 87 or a light chain variable region represented by SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, or 89 to the antibodies with up to 15% variability encompassed by claim 6, as the properties of an antibody comprising the recited heavy and light chain variable regions are not predictive of the full genus of proteins that can be generated.
The instant application has not provided a sufficient description showing possession of the necessary functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus of polypeptides encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. § 112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 48 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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 Vas-Cath, p. 1117). The specification does not "clearly allow persons of ordinary skill in
the art to recognize that [he or she] invented what is claimed." (See Vas-Cath, p. 1116). Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., Inc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Meeting the written description threshold requires showing that the applicant was in
“possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support
need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein
v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning —
i.e., what the written description and knowledge in the art would lead one to speculate as to
modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also
ensures that when a patent claims a genus by function, the specification recites sufficient materials to
accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3.
Given the claimed broadly class of polypeptides, in the absence of sufficient disclosure of relevant
identifying characteristics, the patentee must establish “a reasonable structure-function correlation”
either within the specification or by reference to the knowledge of one skilled in the art with functional
claims. There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed polypeptides to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d 1559, 43, USPQ2d 1398.
WRITTEN DESCRIPTION #2
Claim 9 is rejected under 35 U.S.C. 112(a), 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, at the time the application was filed, had possession of the claimed invention.
Claim 9 recites the antibody or antigen fragment can be a human antibody, however the instant application only discloses humanized anti-CCR8 antibodies.
The instant specification defines “human antibody" as an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and/or antibodies comprising at least one human heavy and/or light chain polypeptide. Whereas a "humanized antibody" is defined as a non-human antibody that is modified to increase the sequence homology to that of a human antibody, such that the antigen-binding properties of the antibody are retained, but its antigenicity in the human body is reduced [0110-0111]. The specification further discloses that monoclonal antibodies can be produced by a hybridoma which includes a B cell obtained from a transgenic nonhuman animal, having a genome comprising a human heavy chain transgene and a light chain transgene [0107].
Mallbris et al. (Clin Aesthetic, 2016; 9(7):1-3) discloses that the distinction between human and humanized antibodies is that fully human mAbs can be developed in transgenic mice that have been genetically engineered with the human immunoglobulin locus while humanized mAbs are initially generated in wild type mice with a native genome bearing the mouse immunoglobulin locus. Portions of the initial antibody produced conferring specificity and affinity (mouse derived) are then grafted onto a human antibody sequence utilizing molecular engineering technology to generate a humanized mAb. This can result in mAbs that have high human amino acid sequence homology, with differences limited to complementarity determining regions (CDRs) within the variable region of the antibody. The specification discloses the structure of humanized anti-CCR8 antibodies that were generated by grafting the CDRs of the lead antibodies into selected human IgG frameworks. However, the instant application has not provided a sufficient description showing possession of human anti-CCR8 monoclonal antibodies as claimed. The Court has interpreted 35 U.S.C. § 112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe, Inc., 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 48 USPQ2d 1398 (Fed Cir. 1997)).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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 Vas-Cath, p. 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath, p. 1116).
Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning —i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3.
As such, a person having ordinary skill in the art would not be able to envision a human anti-CCR8 antibody having a human framework and human CDR regions when the instant claims recite a humanized antibody having mouse CDRs and human framework regions.
ENABLEMENT #1
Claim 6 is rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant has claimed an anti-CCR8 antibody or fragment thereof comprising a heavy chain variable region with a sequence that is at least 85% identical to SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, 87, 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 or a light chain variable region with a sequence that is at least 85% identical to SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, 89, 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111.
The specification disclosure is insufficient to enable one skilled in the art to practice the
invention as claimed without an undue amount of experimentation. Undue experimentation must be
considered in light of factors including: the breadth of the claims, the nature of the invention, the state
of the prior art, the level of one of ordinary skill in the art, the level of predictability in the art, the
amount of direction provided by the inventor, the existence of working examples, and the quantity of
experimentation needed to make or use the invention, see In re Wands, 858 F.2d at 737, 8 USPQ2d at
1404 (Fed. Cir. 1988).
In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) states, “The amount of guidance or
direction needed to enable the invention is inversely related to the amount of knowledge in the state of
the art as well the predictability in the art.” “The “amount of guidance or direction” refers to that
information in the application, as originally filed, that teaches exactly how to make or use the invention.
The more that is known in the prior art about the nature of the invention, how to make, and how to use
the invention, and the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the invention and the
art is unpredictable, the specification would need more detail as to how to make and use the invention
in order to be enabling” (MPEP § 2164.03). The MPEP further states that physiological activity can be
considered inherently unpredictable. With these teachings in mind, an enabling disclosure,
commensurate in scope with the breadth of the claimed invention, is required.
Claim 6 is directed to an antibody heavy chain variable region that is at least 85% identical to SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, 87, 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 or an antibody light chain variable region that is at least 85% identical to SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, 89, 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111. However, the disclosure only recites 16 antibody clones comprising heavy chain variable region amino acid sequences SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, or 87 and light chain variable region amino acid sequences 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, or 89. Thus, it would be difficult for one of ordinary skill in the art to envisage a polypeptide that is 85% identical to the heavy or light chain variable regions of the anti-CCR8 antibodies that were generated that would also have the same properties as the amino acid sequences recited in the instant claims.
For example, MedlinePlus (https://medlineplus.gov/, 2020) teaches that gene variants can alter the function of essential proteins depending on where they occur, with deletion and insertion causing alterations to the secondary structure due to frame shift. Iengar et al. (Nucleic Acids Res, 2012; 40(14):6401–6413) further teaches that frameshift mutations can cause loss of significant function of proteins [Abstract].
The disclosure does not specify how the sequences may vary (i.e., insertion, deletion, substitution) or where in the sequence such variation may occur. Therefore, it can be considered that the inventions defined by claim 6 encompass countless possible substitutions.
There are at least up to 17 possible substitutions that can be made in the heavy chain variable region and/or light chain variable region when considering a polypeptide at least 85% identical to the recited sequences. Combinations of single or double substitutions further multiply the possibilities. Additionally, the variation could occur anywhere in the sequence e.g., three in a row, spread over the entire sequence). However, which residues are critical for binding is highly unpredictable and the instant application has not provided any correlation between what specific structure is needed for binding human CCR8, as seen by the binding results that show the 16 antibody clones possess significantly different binding affinities, with EC50s ranging from 20.56 nM to 0.195 nM.
Thus, based on the unpredictability of the art and the breadth of the claims, the instant
specification must provide a sufficient and enabling disclosure commensurate in scope with the instant
claims. It would require enormous amount of trial and error in order to obtain a monoclonal antibody that binds human CCR8 than the specific heavy and light chain variable domain amino acid sequences described in the detailed description of the invention. This is not in commensurate in scope with the instant claims, which encompass making up to 17 substitutions in each heavy and light chain amino acid sequence to obtain a polypeptide that can bind human CCR8. Thus, it would require undue experimentation to practice the full scope of the claimed method. Specifically, one cannot envisage a polypeptide having at least 85% to SEQ ID NO: 1, 9, 15, 21, 28, 31, 39, 46, 54, 57, 62, 66, 71, 78, 82, 87, 90, 92, 94, 96, 100, 102, 104, 106, 108, or 110 or a polypeptide having at least 85% to SEQ ID NO: 5, 11, 18, 25, 29, 35, 43, 50, 56, 61, 64, 68, 75, 81, 85, 89, 91, 93, 95, 97, 98, 99, 101, 103, 105, 107, 109, or 111 and also having the same properties as the antibody recited in the instant claims. However, the explicit examples provided in the instant specification fall within a genus that is not fully enabled, including polypeptides that are 85% to 99% identical to the recited sequences.
ENABLEMENT #2
Claims 24 and 26 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treating
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP § 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
Claim 24 is drawn to a method for treating a disease mediated by CCR8 and/or CCL1, which comprises administering an effective amount of the instantly claimed monoclonal anti-CCR8 antibody or an antigen-binding fragment thereof to a subject in need, wherein said disease is cancer, neuropathic pain or IgG4-related disease.
Claim 26 further limits the cancer to breast cancer, gastric cancer, ovarian cancer, liver cancer, colon cancer, and pancreatic cancer, further limits the neuropathic pain to pain induced by diabetes or spinal cord injury, and further limits IgG4-related diseases to sclerosing cholangitis.
Regarding neuropathic pain, Cavalli et al. (Int J Immunopathol Pharmacol, 2019; 33:2058738419838383) teaches it is characterized by abnormal hypersensitivity to stimuli (hyperalgesia) and nociceptive responses to non-noxious stimuli (allodynia). The conditions that determine the onset of neuropathic pain are heterogeneous, such as metabolic disorders, neuropathy caused by viral infections, and autoimmune diseases affecting the central nervous system (CNS).
Regarding IgG4-related diseases, Stone et al. (N Engl J Med, 2012; 366:539-551) teaches IgG4-related disease is a fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and storiform fibrosis. IgG4-related disease has been described in virtually every organ system: the biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, meninges, aorta, breast, prostate, thyroid, pericardium, and skin [Introduction].
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
Regarding neuropathic pain, Brooks et al. (Clinical Pharmacist, 2017; 9(12): DOI:10.1211/PJ.2017.20203641) teaches common peripheral neuropathies include painful diabetic neuropathy that is associated with poor quality of life. Effective first and second-line therapies include tricyclic antidepressants, duloxetine, venlafaxine, gabapentin, pregabalin and topical lidocaine [Key Points]. Patients with neuropathic pain typically do not respond to traditional analgesics (paracetamol, NSAIDs) or weak opioids because these do not focus on treating the types of symptoms associated with neuropathic pain and many patients do not achieve satisfactory pain relief even with evidence-based treatment, or do not tolerate effective doses because of adverse effects.
Regarding IgG4-related disease, Khosroshahi et al. (Arthritis & Rheumatology, 2015; 67: 1688-1699) teaches that it can affect multiple organs and lead to tumefactive, tissue-destruction lesions and organ failure. Diagnosis is complicated by the many conditions that can mimic the disease. The disease is often mistaken for a malignancy, an infection or other immune-mediated conditions, such as Sjögren’s syndrome, giant cell arteritis or granulomatosis with polyangiitis. One finding is the importance of accurate and early diagnosis to ensure optimal management of the disease that can affect many organs. Although IgG4-related disease generally has a subacute presentation, irreversible injury to some organs can occur within weeks or months if effective therapy is not initiated. Once fibrosis is established, therapeutic options are limited.
Given the lack of predictability in the treatment of neuropathic pain or treatment of IgG4-related diseases, one of skill in the art would have to engage in undue experimentation to first identify individuals to which the instant method would apply and treat patients with the specific neuropathic pain or IgG4-related disease.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples;
The instant specification sets forth in vivo examples testing the anti-tumor efficacy of the 16 anti-CCR8 antibodies in a breast cancer mouse model, with only 5 demonstrating a significant anti-tumor effect [Example 4]. One candidate antibody was further humanized and used to effectively treat mice with lung and liver cancer [Example 14].
However, the antibodies were never tested in vitro or in vivo as a treatment for neuropathic pain or IgG4-mediated disease. Therefore, the only embodiment that is enabled is treatment of CCR8/CCL1 mediated cancer . One of skill in the art would be required to engage in extensive, difficult experimentation to first develop criteria for identification of other types of cancer, neuropathic pain, and IgG4-related diseases to which the method can apply which is known to be unpredictable as indicated above. This required experimentation is undue.
In conclusion, the claimed invention does not provide enablement for treatment of neuropathic pain or IgG4-related diseases. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter:
Claim 1 is drawn to a monoclonal antibody or an antigen-binding fragment thereof which comprises a HCDR1, a HCDR2 and a HCDR3 of SEQ ID NOs: 58, 79, and 80, respectively, and comprising a light chain variable region comprising a LCDR1, a LCDR2 and a LCDR3 of SEQ ID NOs: 6, 7, and 14, respectively, wherein the antibody or an antigen-binding fragment thereof specifically binds CCR8.
There is no prior art that teaches or suggests an anti-CCR8 monoclonal antibody with the specific CDR amino acid sequences. The closest prior art, CA3124332 is directed towards a monoclonal antibody that specifically bindis human CCR8, however, does not teach or suggest the presently claimed anti-CCR8 monoclonal antibody with the specific sequences as recited in the instant claims.
Claims 1, 10-11, and 16-17 are allowable pending the correction of the minor informalities set forth above.
Claims 4-5, 8, and 22 are allowed.
Conclusion
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 MAUREEN DRISCOLL whose telephone number is (571) 270-0730. The examiner can normally be reached Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642
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