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 .
Claims 2, 14-15, 20, and 25 have been cancelled.
Drawings
The replacement drawings for Figure 10 and Figure 11A were received on 8/7/2023. These drawings are acceptable.
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, 3-13, 16-19, and 21-24 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.
Independent claim 1 was amended on 8/7/2023 to recite “comprises at least one lysine residue (K), in which the amino group of the side chain of the at least one lysine is acylated and is further covalently linked, via a thioether bond, to the monoclonal antibody or the antigen binding fragment.” No basis was pointed to for these limitations and none is apparent. There does not appear to be a general disclosure of acylation, particularly combined with a general disclosure of thioether bonds.
In addition, claim 1 as amended includes acylating all of the lysines (i.e. Z4, Z7, Z9, Z11, Z22, Z23, and Z30) and linking each covalently via a thioether bond to the monoclonal antibody. This is interpreted as meaning the same monoclonal antibody, not linking multiple monoclonal antibodies. Basis is not seen for this.
With respect to claims 3 and 4, no basis has been pointed to and none is apparent for the added limitation “at least one of Z7, Z9, Z11, Z22, Z23, and Z30 in Formula I is lysine (K).”
The claims constitute new matter.
Claims 17-19, and 21-23 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 methods as discussed below, does not reasonably provide enablement for all methods of treatment encompassed. 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.
Claim 17 is directed to a method for treating or preventing a disease or disorder in a subject in need thereof, wherein said disease or disorder is selected from the group consisting of obesity, type I or type II diabetes, metabolic syndrome, insulin resistance, impaired glucose tolerance, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypoglycemia due to congenital hyperinsulinism (CHI), dyslipidemia, atherosclerosis, diabetic nephropathy, and hypertension, unmanaged cholesterol and/or lipid levels, osteoporosis, inflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), renal disease, and eczema, the method comprising administering to the subject in need thereof an effective amount of the pharmaceutical composition of claim 16.
Other than prevention, claim 17 does not require any particular therapeutic effect to be achieved by the “effective amount” administered.
Claim 18 is directed to a method of reducing food intake in a subject in need thereof.\
Claim 19 is directed to a method of modulating Y2 receptor activity in a subject in need thereof.
Neither the conjugate of claim 1 nor the pharmaceutical compositions of claim 16 indicate that the conjugated monoclonal antibody is non-targeting. That is, the specification indicates that the monoclonal antibodies are non-targeting and function to increase half-life of the PYY. The specification indicates that the monoclonal antibodies have been made non-functioning by substituting a cysteine within a CDR and conjugating to that cysteine. See at least specification paragraph [0062]. As the claims are directed to any monoclonal antibody that can bind to any antigenic target, it does not appear that the cyclic PYY will reach the intended target tissue for treating any of the recited conditions in claims 17-19. For example, the monoclonal antibody could target an androgen receptor or a neonatal Fc receptor (FcRn) or any other target and sequester the cyclic PYY.
The specification and prior art of record do not provide any evidence that administration of any of the claimed conjugates will prevent any of the recited diseases or disorders in claim 17.
At least paragraph [0190] defines “treating” as amelioration or reversal of at least one measurable physical parameter related to the disease, disorder, or condition. “Treatment” also refers to causing regression, preventing the progression, or at least slowing down the progression of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an alleviation, prevention of the development or onset, or reduction in the duration of one or more symptoms associated with the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to prevention of the recurrence of the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to an increase in the survival of a subject having the disease, disorder, or condition. In a particular embodiment, “treat,” “treating,” and “treatment” refer to elimination of the disease, disorder, or condition in the subject (i.e. cure)
As the claim 17 require no particular therapeutic effect, all therapeutic effects encompassed by the claim must be enabled. There is no evidence of record nor any reason to believe that administration of any of the claimed conjugates will cure any of the recited diseases. There is no evidence of record nor any reason to believe that administration of the claimed conjugates will reverse or ameliorate all symptoms of all diseases recited. At least for example, a symptom of diabetes is peripheral neuropathy (i.e. sensory nerve damage). At least for example, a symptom of osteoporosis is bone loss and bone fracture. At least for example, a symptom of obesity is joint damage. There is no evidence of record that sensory nerve damage can be reversed or cured. There is no evidence of record that bone loss or bone fracture can be reversed or cured. There is no evidence of record that joint damage can be reversed or cured.
The scope of the claims is not enabled.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-4, 6-9, 12, 18-19, and 21-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3-4 are confusing in their dependency upon claim 1. While claims 3-4 indicate that at least one of Z7, Z9, Z11, Z22, Z23, and Z30 is K, claims 3-4 also indicates that in each of these positions acylation is optional. This is in conflict with claim 1 which requires acylation and a thioether bond. It is unclear which lysine (K) positions in claims 3-4 meet the acylation and thioether bond limitations of claim 1.
Claim 6 is confusing in its dependency upon claim 1. It does not make clear that the cysteine in the monoclonal antibody is part of the thioether bond required by claim 1. There is no antecedent basis in claim 1 for a linker.
Claim 7 is confusing in its dependency upon claim 6. Claim 1 does not include a linker between the acylation and the thioether bond.
Claim 8 recites an “engineered cysteine.” The specification provides an example of an engineered cysteine as substituting a cysteine into a CDR of an antibody to make it a non-targeting antibody and also so that the cysteine is capable of conjugation; however, there is no limiting definition of what this term means. See for example, specification paragraph [0064 and 0432]. The metes and bounds of the claim cannot be determined.
Claim 9 recites a “conjugate comprising a monoclonal antibody or an antigen binding fragment thereof coupled to a cyclic PYY peptide, wherein the conjugate comprises a sequence selected from the group consisting of SEQ ID NOs: 102-127 or a pharmaceutically acceptable salt thereof, wherein mAb represents the monoclonal antibody or the antigen binding fragment thereof, and ]2 represents that 1 or 2 of the cyclic PYY peptide are covalently conjugated to the mAb.” This claim is confusing in that it appears to be defining a formula that is not present in the claim. It is noted that SEQ ID NOS: 102-127 in the sequence listing are not indicated as being cyclic or connected to monoclonal antibodies. SEQ ID NOS: 102-127 as described on pages 190-199 indicate cyclic homodimeric structures connected to monoclonal antibodies. For purposes of claim interpretation, the sequence listing identification controls. The metes and bounds of the claim cannot be determined.
Claim 12 recites “further comprising a Fc portion.” This does not make clear that the Fc portion is part of the monoclonal antibody in claim 11.
Claim 18 does not make clear what subjects are “in need of” reducing food intake. It is not clear which subjects would be “in need.” While it is presumed that an obese subject might be in need, it is unclear what other subjects might be in need. The metes and bounds of the claim cannot be determined.
Claim 19 does not make clear what subjects are “in need of” modulating Y2 receptor activity. It is noted that “modulating” includes increasing and decreasing receptor activity. It is not clear which subjects would be “in need.” The metes and bounds of the claim cannot be determined.
Claims 21-23 are confusing in their dependency on claim 17. Claim 17 is not limited to treating diabetes. It is unclear why an anti-diabetic agent such as a glucagon-like-peptide-1 receptor modulator (e.g.liraglutide) would be administered in a treatment for osteoporosis, renal disease, or eczema, for example, as recited in claim 17.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-8, 10-13, 16-19, 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,640,544 in view of Eigenbrot et al. (U.S. Patent Application Publication 2007/0092940).
The 12/7/2018 restriction requirement in 15/794,171 (issued as U.S. Patent No. 10,640,544) was withdrawn in the 12/18/2019 Notice of Allowability. A double patenting rejection is not precluded.
Issued claims 3-4 as they depend claim from claim 1 have lysines (K) with haloacetyl groups where the cyclic PYY is conjugated to a monoclonal antibody.. The CDRs of instant claim 10 are found in issued claim 1. Issued claims 6-8 conjugate the cyclic PYY to the monoclonal antibody through the PYY lysine and in particular a cysteine in the monoclonal antibody. See in particular claim 8. See instant claims 6-8. Issued claims 5 and 8-12 provide the limitations of instant claims 5, 8, 11-13, and 16, respectively. Issued claims 13-14 provide the limitations of instant claims 17-19. Issued claims 16-19 provide the limitations of instant claims and 21-24, respectively. The ‘544 claims do not specifically recite a thioether bond.
Eigenbrot et al. discloses conjugating cysteine engineered antibodies to a drug moiety through a thiol reactive group such as a haloacetyl. See at least abstract and paragraph [0160].
It would have been obvious to conjugate the antibody and cyclic PYY peptide of the issued claims through an engineered cysteine in the antibody and the haloacetyl group on the lysine in the cyclic PYY peptide (see at least issued claims 3-4) thereby forming a thioether bond. One would have been motivated to do so in order to form a stable conjugate.
The instant claims are not patentably distinct from the issued claims in view of Eigenbrot et al.
Claims 1, 3-8, 10-13, 16-17, and 21-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,591,379 in view of Eigenbrot et al. (U.S. Patent Application Publication 2007/0092940).
U.S. patent application 16/820,174 (issuing as U.S. Patent No. 11,591,379) is a DIV of U.S. patent application 15/794,171 and did not have a restriction requirement between different inventions. The 12/7/2018 restriction requirement in 15/794,171 (issued as U.S. Patent No. 10,640,544) was withdrawn in the 12/18/2019 Notice of Allowability. A double patenting rejection is not precluded.
Issued claims 3-4 as they depend claim from claim 1 have lysines (K) with haloacetyl groups where the cyclic PYY is conjugated to a monoclonal antibody.. The CDRs of instant claim 10 are found in issued claim 1. The pharmaceutical composition limitations of instant claim 16 are found in issued claim 1. The treatment limitations of instant claim 17 are found in issued claim 1. Issued claims 6-8 conjugate the cyclic PYY to the monoclonal antibody through the PYY lysine and in particular a cysteine in the monoclonal antibody. See in particular claim 8. See instant claims 6-8. Issued claims 5 and 8-11 provide the limitations of instant claims 5, 8, and 11-13, respectively. Issued claims 13-15 provide the limitations of instant claims 21-23, respectively. The ‘379 claims do not specifically recite a thioether bond.
Eigenbrot et al. discloses conjugating cysteine engineered antibodies to a drug moiety through a thiol reactive group such as a haloacetyl. See at least abstract and paragraph [0160].
It would have been obvious to conjugate the antibody and cyclic PYY peptide of the issued claims through an engineered cysteine in the antibody and the haloacetyl group on the lysine in the cyclic PYY peptide (see at least issued claims 3-4) thereby forming a thioether bond. One would have been motivated to do so in order to form a stable conjugate.
The instant claims are not patentably distinct from the issued claims in view of Eigenbrot et al.
Claims 1, 3-8, 10-13, 16-19, and 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,968,265 in view of Eigenbrot et al. (U.S. Patent Application Publication 2007/0092940).
Issued claims 3-4 as they depend claim from claim 1 can have lysines (K) with haloacetyl groups where the cyclic PYY is conjugated to a monoclonal antibody.. The CDRs of instant claim 10 are found in issued claim 1. The pharmaceutical composition limitations of instant claim 16 are found in issued claim 15. The treatment limitations of instant claim 17 are found in issued claim 16. The treatment limitations of instant claims 18-19 are found in issued claims 17-18. Issued claims 6-8 conjugate the cyclic PYY to the monoclonal antibody through the PYY lysine and in particular a cysteine in the monoclonal antibody. See in particular claim 8. See instant claims 6-8. Issued claims 5, 8, and 10-12 provide the limitations of instant claims 5, 8, and 11-13, respectively. Issued claims 20-23 provide the limitations of instant claims 21-24, respectively. The ‘265 claims do not specifically recite a thioether bond.
Eigenbrot et al. discloses conjugating cysteine engineered antibodies to a drug moiety through a thiol reactive group such as a haloacetyl. See at least abstract and paragraph [0160].
It would have been obvious to conjugate the antibody and cyclic PYY peptide of the issued claims through an engineered cysteine in the antibody and the haloacetyl group on the lysine in the cyclic PYY peptide (see at least issued claims 3-4) thereby forming a thioether bond. One would have been motivated to do so in order to form a stable conjugate.
The instant claims are not patentably distinct from the issued claims in view of Eigenbrot et al.
Claims 1, 3-8, 10-13, 16-19, and 21-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,767,354 in view of Eigenbrot et al. (U.S. Patent Application Publication 2007/0092940).
Issued claims 3-4 as they depend claim from claim 1 can have lysines (K) with haloacetyl groups where the cyclic PYY is conjugated to a monoclonal antibody.. The CDRs of instant claim 10 are found in issued claim 1. The pharmaceutical composition limitations of instant claim 16 are found in issued claim 1. The treatment limitations of instant claim 17 are found in issued claim 17. The treatment limitations of instant claims 18-19 are found in issued claims 18-19. Issued claims 6-8 conjugate the cyclic PYY to the monoclonal antibody through the PYY lysine and in particular a cysteine in the monoclonal antibody. See in particular claim 8. See instant claims 6-8. Issued claims 5, 8, and 10-12 provide the limitations of instant claims 5, 8, and 11-13, respectively. Issued claims 21-22 provide the limitations of instant claims 21-23. The ‘354 claims do not specifically recite a thioether bond.
Eigenbrot et al. discloses conjugating cysteine engineered antibodies to a drug moiety through a thiol reactive group such as a haloacetyl. See at least abstract and paragraph [0160].
It would have been obvious to conjugate the antibody and cyclic PYY peptide of the issued claims through an engineered cysteine in the antibody and the haloacetyl group on the lysine in the cyclic PYY peptide (see at least issued claims 3-4) thereby forming a thioether bond. One would have been motivated to do so in order to form a stable conjugate.
The instant claims are not patentably distinct from the issued claims in view of Eigenbrot et al.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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