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 .
1. The Amendment filed September 18, 2025 in response to the Office Action of June 9, 2025, is acknowledged and has been entered. Claims 1-21 are pending and being examined. Claims 1-20 are amended. Claim 21 is new.
Applicants have amended the claims to CHANGE THE INVENTION from a method to a product. The invention has changed from a method of treating a patient who has cancer comprising administering to the patient an antibody comprising CDR SEQ ID NOs 6-11, to the invention of an antibody comprising CDR SEQ ID NOs 6-11. New rejections are set forth below that address these changes.
New Rejections
(necessitated by amendments)
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.
2. Two rejections regarding written description are set forth below in order to separately address two different limitations in the claims.
3. New claim 21 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claim is drawn to an antibody comprising a heavy chain variable domain comprising:
CDR1 comprising the amino acid sequence of SEQ ID NO: 6,
CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 8,
wherein the heavy chain variable domain comprises at most one conservative amino acid substitution in the CDR1, the CDR2, and/or the CDR3, and
a light chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 9,
CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 11,
wherein the light chain variable domain comprises at most one conservative amino acid substitution in the CDR1, the CDR2, and/or the CDR3,
wherein the antibody is adapted for treating a cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5.
Thus, the claims identify the antibody by partial structure and function, wherein: (1) the function is to treat cancer expressing human CXCL1 SEQ ID NO: 5, by binding human chemokine CXCL1 protein comprising SEQ ID NO:5; and (2) the partial structure is an antibody comprising up to one conservative substitution at any amino acid position in one or all of the six CDR SEQ ID NOs:6-11. The claim encompasses a broad genus of substitution variant antibodies having one to six conservative mutations of any amino acids in any of the CDR sequences.
The instant specification discloses in Example 1 a single mouse monoclonal antibody clone designated as HL2401 that is capable of binding CXCL1 and completely blocking CXCL1-CXCR2 binding, and comprises CDR SEQ ID NOs:6-11 (Table 1). Example 3 of the specification demonstrates HL2401 antibody blocking CXCL1-induced HUVEC proliferation and sprouting, reducing invasive potential of T24 and PC3 cells, and having inhibitory effect on HUVEC tube formation as an anti-angiogenic agent. Example 5 of the specification shows administration of HL2401 to mice with bladder cancer (T24) and prostate cancer (PC3) xenografts resulted in the inhibition of endothelial sprouting, the inhibition of cellular invasion, and the diminution of bladder and prostate xenograft growth through the inhibition of angiogenesis and proliferation, and the induction of apoptosis (REF). Example 8 of the specification discloses a humanized version of HL2401 antibody comprising CDR SEQ ID NOs:6-11 can inhibit endothelial cell tube formation. The specification concludes: anti-CXCL1 neutralizing monoclonal antibody (HL2401) of the present disclosure can: a) inhibit cellular proliferation, b) inhibit cellular invasion, c) inhibit endothelial sprouting, and d) result in the inhibition of subcutaneous xenograft tumors expressing CXCL1 via reduction in both proliferation and angiogenesis, and the induction of apoptosis.
Thus, the instant specification describes a single monoclonal anti-CXCL1 antibody HL2401 comprising CDR SEQ ID NOs:6-11 that binds human CXCL1 comprising SEQ ID NO:5 and treats cancer expressing CXCL1 as claimed. The specification fails to disclose any exemplary sequences of a conservative substitution variant antibody that possesses the functions claimed. The specification fails to disclose which of the amino acids of the six CDR SEQ ID NOs:6-11 can be substituted with which amino acids and still predictably function as claimed.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative conservative substitution variant antibodies that function to bind CXCL1 SEQ ID NO:5 and are adapted to treat cancer, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
Although Applicants may argue that it is possible to screen for conservative substitution variant antibodies that bind CXCL1 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The CXCL1 SEQ ID NO:5 antigen provides no information about the structure of an antibody that binds to it or treats cancer.
In this case, the only factor present in the claim is a recitation of the antibody function: “adapted for treating a cancer that expresses chemokines CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5” that requires a function of binding SEQ ID NO:5, and a recited partial sequence structure comprising up to six conservative amino acid substitutions in one or all of the CDR SEQ ID NOs critical to the CXCL1 binding and treating function. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose a single exemplary conservative substitution variant antibody sequence that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. The specification fails to provide any substitution variant structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of substitution variant antibody sequences for the genus of substitution variant antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed substitution variant antibody genus required to perform the claimed method.
In the instant case, the specification discloses a single monoclonal anti-CXCL1 antibody HL2401 comprising CDR SEQ ID NOs:6-11 that functions as claimed. The claims broadly encompass any conservative substitution variant antibody comprising up to one amino acid substitution in each CDR sequence, and that is required to bind CXCL1 SEQ ID NO:5 and treat cancer. Applicants have not established any reasonable structure-function correlation with regard to the sequences in the CDRs that can be altered and still maintain CXCL1-binding function and be adapted to treat cancer expressing CXCL1. The instant claims attempt to claim a vast genus of conservative substitution variant antibodies that would achieve a desired result, i.e., bind CXCL1 SEQ ID NO:5 and treat cancer expressing CXCL1, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only a single species of monoclonal antibody comprising only CDR SEQ ID NOs:6-11 that binds to CXCL1 SEQ ID NO:5 and treats cancer. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of substitution variant antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single mouse monoclonal anti-CXCL1 antibody to the structure of any and all conservative substitution variants of the antibody, as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Given the lack of representative examples to support the full scope of the claimed antibody variants, and lack of reasonable structure-function correlation with regards to the variant CDR sequences that provide CXCL1 SEQ ID NO:5-binding and cancer-treating functions, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of conservative substitution variant antibodies of the single disclosed HL2401 CXCL1 antibody that is required to practice the claimed invention.
Examiner Suggestion: Delete the phrases in claim 21 of: “wherein the heavy chain variable domain comprises at most one conservative amino acid substitution in the CDR1, the CDR2, and/or the CDR3” and “wherein the light chain variable domain comprises at most one conservative amino acid substitution in the CDR1, the CDR2, and/or the CDR3”.
4. Claims 1, 8-11, 20, and 21 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an antibody comprising a heavy chain variable domain comprising:
CDR1 comprising the amino acid sequence of SEQ ID NO: 6,
CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and
a light chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 9,
CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 11,
wherein the antibody is adapted for treating a cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5.
Thus, the claims initially identify the antibody by CDR sequences, and then the claims recite that the claimed antibody can be “adapted” for treating the claimed cancer. This reasonably encompasses a genus of antibodies comprising any changes anywhere to the antibody for adaptation, including changes to the CDR sequences. The claims encompass a broad genus of adapted, altered antibodies having any adaptations and changes anywhere, including in any or all of the six CDR sequences.
The only mention of the word “adapt” anywhere in the specification is in the last published paragraph of the specification [301]:
It will be understood that each of the elements described above, or two or more together may also find a useful application in other types of methods differing from the type described above. Without further analysis, the foregoing will so fully reveal the gist of the present disclosure that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this disclosure set forth in the appended claims. The foregoing embodiments are presented by way of example only; the scope of the present disclosure is to be limited only by the following claims.
This paragraph does not provide or define any recognizable structural adaptations to the antibody for treating cancer, as broadly encompassed by the instant claims.
The instant specification discloses in Example 1 a single mouse monoclonal antibody clone designated as HL2401 that is capable of binding CXCL1 and completely blocking CXCL1-CXCR2 binding, and comprises CDR SEQ ID NOs:6-11 (Table 1). Example 3 of the specification demonstrates HL2401 antibody blocking CXCL1-induced HUVEC proliferation and sprouting, reducing invasive potential of T24 and PC3 cells, and having inhibitory effect on HUVEC tube formation as an anti-angiogenic agent. Example 5 of the specification shows administration of HL2401 to mice with bladder cancer (T24) and prostate cancer (PC3) xenografts resulted in the inhibition of endothelial sprouting, the inhibition of cellular invasion, and the diminution of bladder and prostate xenograft growth through the inhibition of angiogenesis and proliferation, and the induction of apoptosis (REF). Example 8 of the specification discloses a humanized version of HL2401 antibody comprising CDR SEQ ID NOs:6-11 can inhibit endothelial cell tube formation. The specification concludes: anti-CXCL1 neutralizing monoclonal antibody (HL2401) of the present disclosure can: a) inhibit cellular proliferation, b) inhibit cellular invasion, c) inhibit endothelial sprouting, and d) result in the inhibition of subcutaneous xenograft tumors expressing CXCL1 via reduction in both proliferation and angiogenesis, and the induction of apoptosis.
Thus, the instant specification describes a single monoclonal anti-CXCL1 antibody HL2401 comprising CDR SEQ ID NOs:6-11 that binds human CXCL1 comprising SEQ ID NO:5 and treats cancer expressing CXCL1 as claimed. The specification fails to disclose any exemplary “adapted” antibodies that possesses the functions claimed. The specification fails to disclose what structural adaption changes can occur to the antibody, including within its CDR sequences, and still predictably function as claimed.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative adapted antibodies that function to treat cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
Although Applicants may argue that it is possible to screen for antibody adaptations that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The CXCL1 SEQ ID NO:5 antigen provides no information about the structure of an antibody that binds to it or treats cancer.
In this case, the claimed limitation of “adapted for treating a cancer that expresses chemokines CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5” opens the claimed genus of antibodies up to any structural variants. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose a single exemplary adaptation that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. The specification fails to provide any adaptation features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibodies or adaptations for the genus of adapted antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed adapted antibody genus required to perform the claimed function.
In the instant case, the specification discloses a single monoclonal anti-CXCL1 antibody HL2401 comprising CDR SEQ ID NOs:6-11 that functions as claimed. The claims broadly encompass any variant antibody comprising any adaptations, and that is required to treat cancer as claimed. Applicants have not established any reasonable structure-function correlation with regard to the sequences in the CDRs that can be altered and still maintain CXCL1-binding function and be adapted to treat cancer expressing CXCL1. The instant claims attempt to claim a vast genus of variant antibodies that would achieve a desired result, i.e., bind CXCL1 SEQ ID NO:5 and treat cancer expressing CXCL1, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only a single species of monoclonal antibody comprising only CDR SEQ ID NOs:6-11 that binds to CXCL1 SEQ ID NO:5 and treats cancer. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of adapted antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single mouse monoclonal anti-CXCL1 antibody to the structure of any and all adapted variants of the antibody, as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Given the lack of representative examples to support the full scope of the claimed adapted antibody variants, and lack of reasonable structure-function correlation with regards to what structural changes can occur and still provide CXCL1 SEQ ID NO:5-binding and cancer-treating functions, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of the broadly claimed genus of adapted antibodies.
Examiner Suggestion: Delete the phrase in claim 1 and 21 of: “wherein the antibody is adapted for treating a cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claim(s) 1, 9-11, 20, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Application Publication 2019/0292604, Essner, claiming priority to March 20, 2018, as evidenced by the instant specification.
Claim interpretation: As stated above, the rejected claims are interpreted to broadly encompass antibodies having any adaptions or structural changes from the instantly claimed sequences, so long as the antibody functions to treat cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5.
Essner teaches antibody HL2401 that functions to bind human CXCL1 and treat cancer, including bladder and prostate cancer, and combining the antibody into a pharmaceutical composition with adjuvant, such as IL-2 ([32]; [74]; [78-79] claims 11-14).
As evidenced by the instant specification, antibody HL2401 inherently binds human CXCL1 SEQ ID NO:5 ([161-163]; Figure 1; Example 1). Therefore, the HL2401 antibody taught by Essner is inherently an antibody that is adapted for treating a cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5 and inherently binds SEQ ID NO:5.
Examiner Suggestion: Delete the phrase in claim 1 and 21 of: “wherein the antibody is adapted for treating a cancer that expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO:5”.
Maintained Rejections
(amendments addressed)
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
6. Claims 1-21 remain/ are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,292,832. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patent is claiming methods of administering an anti-CXCL1 antibody comprising the same sequences, and with the same adjuvant, to treat cancer, and claims the antibody functions to bind to human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5, thereby rendering obvious the antibody composition of the instant claims. The US Patent claims:
1. A method of treating a patent who has cancer, comprising administering to the patient an antibody comprising a heavy chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 6,
CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and a light chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 9,
CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 11,
wherein the cancer is bladder cancer or prostate cancer.
2. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14 or 18 .
3. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30 or 32 .
4. The method of claim 1, wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 14 or 18.
5. The method of claim 1, wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 30 or 32.
6. The method of claim 1, wherein the heavy chain variable domain comprises
CDR1 consisting of the amino acid sequence of SEQ ID NO: 6,
CDR2 consisting of the amino acid sequence of SEQ ID NO: 7, and
CDR3 consisting of the amino acid sequence of SEQ ID NO: 8, and the light chain variable domain comprises
CDR1 consisting of the amino acid sequence of SEQ ID NO: 9,
CDR2 consisting of the amino acid sequence of SEQ ID NO: 10, and
CDR3 consisting of the amino acid sequence of SEQ ID NO: 11.
7. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16, 20, 22, or 24 .
8. The method of claim 1, wherein the light chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 26 and the heavy chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 27.
9. The method of claim 1, wherein the antibody is in the form of a composition comprising an adjuvant, and optionally, a pharmaceutically acceptable carrier, and optionally, pharmaceutically acceptable excipients and/or stabilizers.
10. The method of claim 9, wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.
11. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14.
12. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 18.
13. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30.
14. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32.
15. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16.
16. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 20.
17. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 22.
18. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 24.
19. The method of claim 1, wherein the antibody binds to a human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5.
7. Claims 1-21 remain/ are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,760,796. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patent is claiming methods of administering an anti-CXCL1 antibody comprising the same sequences to treat cancer expressing human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5 and with the same adjuvant, thereby rendering obvious the antibody composition of the instant claims. The US Patent claims:
1. A method of treating a patient who has cancer comprising administering to the patient an antibody comprising
a heavy chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 6,
CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and
a light chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 9,
CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 11,
wherein the cancer expresses human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5.
2. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14 or 18.
3. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30 or 32.
4. The method of claim 1, wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 14 or 18.
5. The method of claim 1, wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 30 or 32.
6. The method of claim 1, wherein
the heavy chain variable domain comprises
CDR1 consisting of the amino acid sequence of SEQ ID NO: 6,
CDR2 consisting of the amino acid sequence of SEQ ID NO: 7, and
CDR3 consisting of the amino acid sequence of SEQ ID NO: 8, and
the light chain variable domain comprises
CDR1 consisting of the amino acid sequence of SEQ ID NO: 9,
CDR2 consisting of the amino acid sequence of SEQ ID NO: 10, and
CDR3 consisting of the amino acid sequence of SEQ ID NO: 11.
7. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16, 20, 22, or 24.
8. The method of claim 1, wherein the light chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 26 and the heavy chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 27.
9. The method of claim 1, wherein the cancer is bladder cancer or prostate cancer.
10. The method of claim 1, wherein the antibody is in the form of a composition comprising an adjuvant, and optionally, a pharmaceutically acceptable carrier, and optionally, pharmaceutically acceptable excipients and/or stabilizers.
11. The method of claim 10, wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.
12. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14.
13. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 18.
14. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30.
15. The method of claim 1, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32.
16. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16.
17. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 20.
18. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 22.
19. The method of claim 1, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 24.
20. The method of claim 1, wherein the antibody binds to a human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5.
Response to Arguments
8. Applicants state they will file a terminal disclaimer once the claims are otherwise in condition for allowance.
9. No terminal disclaimer has been field and the claims remain rejected.
New Rejection
(necessitated by amendments)
10. Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11, 267,881. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patent is claiming overlapping antibodies comprising the same sequences, functions, and pharmaceutical composition comprising adjuvant with the instant claims. The US Patent claims:
1. An isolated anti-human chemokine CXCL1 monoclonal antibody or an isolated antigen binding fragment thereof, comprising
a heavy chain variable domain comprising
a complementary-determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO: 6,
CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and
a light chain variable domain comprising
CDR1 comprising the amino acid sequence of SEQ ID NO: 9,
CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and
CDR3 comprising the amino acid sequence of SEQ ID NO: 11; and
wherein the antibody or the antigen-binding fragment thereof binds to human chemokine CXCLI protein comprising the amino acid sequence of SEQ ID NO: 5.
2. The antibody or the antigen-binding fragment thereof of claim 1, wherein the antibody comprises an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 2 and an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 4.
3. The antibody or the antigen-binding fragment thereof of claim 2, wherein the immunoglobulin light chain comprises at least one amino acid addition, substitution, insertion, and/or deletion in the amino acid sequence of SEQ ID NO:2.
4. The antibody or the antigen-binding fragment thereof of 2, wherein the immunoglobulin heavy chain comprises at least one amino acid addition, substitution, insertion, and/or deletion in the amino acid sequence of SEQ ID NO:4.
5. The antibody or the antigen-binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof is labeled with a toxin.
6. The antibody or the antigen-binding fragment thereof of claim 1, wherein the antibody or the antigen-binding fragment thereof is labeled with a radionucleotide, a fluorescent dye, a fluorescent protein, an enzyme, biotin and/or streptavidin.
7. The antibody or the antigen-binding fragment thereof of claim 6, wherein the antibody or antigen binding fragment thereof is labelled with a radionucleotide.
8. The antibody or the antigen-binding fragment thereof of claim 6, wherein the fluorescent protein is phycoerythrin (PE), allophycocyanin (APC), or green fluorescent protein (GFP).
9. The antibody or the antigen-binding fragment thereof of claim 6, wherein the enzyme is horseradish peroxidase, alkaline phosphatase, or glucose oxidase.
10. An isolated nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof of claim 1.
11. The nucleic acid molecule of claim 10, wherein the nucleic acid molecule encoding the immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 2 comprises the nucleotide sequence of SEQ ID NO: 1.
12. The nucleic acid molecule of claim 11, wherein the nucleic acid molecule encoding the immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 4 comprises the nucleotide sequence of SEQ ID NO: 3.
13. A vector comprising the nucleic acid molecule of claim 10.
14. A host cell comprising the nucleic acid molecule of claim 10.
15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one active ingredient selected from the group consisting of the antibody and the antigen-binding fragment thereof of claim 1.
16. The composition of claim 15, wherein the pharmaceutically acceptable carrier is saline, Ringer's solution, dextrose solution, and/or solid hydrophobic polymer.
17. The composition of claim 16, wherein the solid hydrophobic polymer is film, liposome, or microparticle.
18. The composition of claim 15, further comprising an adjuvant.
19. An isolated anti-human chemokine CXCL1 monoclonal antibody or an isolated antigen binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof binds to human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5, and wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable domain comprising complementarity-determining region (CDR) 1 consisting of the amino acid sequence of SEQ ID NO: 6, CDR2 consisting of the amino acid sequence of SEQ ID NO: 7, and CDR3 consisting of the amino acid sequence of SEQ ID NO: 8, and a light chain variable domain comprising CDR1 consisting of the amino acid sequence of SEQ ID NO: 9, CDR2 consisting of the amino acid sequence of SEQ ID NO: 10, and CDR3 consisting of the amino acid sequence of SEQ ID NO: 11.
20. The antibody or the antigen-binding fragment thereof of claim 19, wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO:12.
21. The antibody or the antigen-binding fragment thereof of claim 19, wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 13 or 15.
22. The antibody or the antigen-binding fragment thereof of claim 19, comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 14, 16, 17, and 18.
23. The antibody or the antigen-binding fragment thereof of claim 19, wherein the light chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 19.
24. The antibody or the antigen-binding fragment thereof of claim 19, wherein the heavy chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 20.
11. Conclusion: No claim is allowed.
12. All other objections and rejections recited in the Office Action mailed June 9, 2025 are hereby withdrawn in view of amendments.
Conclusion
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 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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/Laura B Goddard/Primary Examiner, Art Unit 1642