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 .
Applicant's arguments filed 3/2/2026 have been fully considered but they are not persuasive.
Claims 2, 8-9, 12, 14-15, 18-20, and 25 have been cancelled.
Claim Objections
Claim 5 is objected to because of the following informalities: The claim recites SEQ ID Nos:1, and 73-100, ,” and is improperly punctuated. Appropriate correction is required.
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, 3-7, 10-11, 13, 16-17, 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 has now been amended to recite “only one of Z7, Z9, Z11, Z22, and Z23 in Formula I is lysine (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.” Basis was stated to be in paragraphs [0069 and 0229] of U.S. Patent Application Publication 2023/0365644. This is not agreed with. These paragraphs provide this disclosure in the context of an engineered cysteine residue of the monoclonal antibody. In particular, paragraph [0229] discloses engineering a cysteine into HCDR3. The recitation of a thioether bond does not set forth this disclosure. Note that the specification discloses the term “thioether” only in specification paragraph [0118] and this disclosure is not in the context of Formula I. See also Figure 1 and paragraphs [0030, 0062, 0064] of the specification. There does not appear to be a general disclosure of acylation, particularly combined with a general disclosure of thioether bonds. See original claims 6-8 and paragraphs [0068-0069]. Furthermore, Formula I of claim 1 (as amended) permits a cyclic peptide where none of Z7, Z9, Z11, Z22, and Z23 is lysine (i.e. Z7 is A, Z9 is G, Z11 is D, Z22 is A, and Z23 is S), and thus the cyclic peptide is not coupled to the monoclonal antibody in this embodiment. Claim 1 is not interpreted as requiring that one of Z7, Z9, Z11, Z22, and Z23 must be lysine. It is interpreted as meaning that if one of these positions is selected as being lysine, then none of the other recited positions can be lysine. No basis is seen for the amendments to claim 1.
Claim 6 as currently amended does not reflect an engineered cysteine residue either. Again, see original claims 6-8.
With respect to claim 7 as it depends from claims 1 and 6, claim 1 requires a thioether bond which is the linker covalently coupling the antibody to the cyclic PYY peptide in claim 6. Claim 7 makes clear that the linker can be a bond. Note that claim 6 includes coupling at Z30 which is not an embodiment of claim 1. In claim 1, Z30 (when present) can be L, W, or K; however, K at this position is not acylated and/or covalently linked to the antibody according to claim 1. Claim 7 provides that the linker can be a bond (broader than the thioether bond in claim 1) or other recited linkers. To the degree that claim 7 is combining the recited linkers with the thioether bond required by claim 1, basis is not seen.
The claims constitute new matter.
Claims 17 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, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH), the method comprising administering to the subject in need thereof an effective amount of the pharmaceutical composition of claim 16.
Claim 21 has been amended to be directed to the disease or disorder of Type II diabetes.
Other than prevention, claim 17 does not require any particular therapeutic effect to be achieved by the “effective amount” administered.
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. Applicant’s 3/2/2026 response did not address this.
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 claims 17 and 21. Applicant’s 3/2/2026 response did not address this.
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 claims 17 and 21 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 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 joint damage can be reversed or cured. Applicant’s 3/2/2026 response did not address this.
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 1, 3-7, 10-11, 16-17, and 21-24 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.
Claim 1 is confusing in reciting “only one of Z7, Z9, Z11, Z22, and Z23 in Formula I is lysine (K), in which the amino group of the side chain of the at least one lysine is acylated.” As written, the claim is inconsistently directed to both “only one” and “at least one.” Dependent claims 3-4 have been interpreted to mean that only one of Z7, Z9, Z11, Z22, and Z23 in Formula I is lysine (K). Otherwise, these claims would not be properly dependent upon claim 1. Furthermore, Formula I of claim 1 (as amended) permits a cyclic peptide where none of Z7, Z9, Z11, Z22, and Z23 is lysine (i.e. Z7 is A, Z9 is G, Z11 is D, Z22 is A, and Z23 is S), and thus the cyclic peptide is not coupled to the monoclonal antibody in this embodiment. Claim 1 is not interpreted as requiring that one of Z7, Z9, Z11, Z22, and Z23 must be lysine. It is interpreted as meaning that if one of these positions is selected as being lysine, then none of the other recited positions can be lysine.
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. Claim 6 is confusing in including coupling at Z30 which is not an embodiment of claim 1. In claim 1, Z30 (when present) can be L, W, or K; however, K at this position is not acylated and/or covalently linked to the antibody according to claim 1.
Claim 7 is confusing in its dependency upon claim 6. Claim 1 does not include a linker between the acylation and the thioether bond. See new matter rejection above. Claim 7 is also confusing as the linker can be a bond (broader than the thioether bond in claim 1). The claim does not appear to be properly dependent.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. SEQ ID NO: 77 does not meet the structural limitations of Formula I in claim 1. It does not contain the sequence ASPEELNRYY. It contains the sequence ASPEELNRKY. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3-7, 10-11, 13, 16-17, and 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 6-7. Issued claims 5 and 8-12 provide the limitations of instant claims 5, 11, 13, and 16, respectively. Issued claims 13-14 provide the limitations of instant claim 17. 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, 3-7, 10-11, 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 6-7. Issued claims 5 and 8-11 provide the limitations of instant claims 5, 11, and 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, 3-7, 10-11, 13, 16-17, 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. 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 6-7. Issued claims 5, 8, and 10-12 provide the limitations of instant claims 5, 8, 11, and 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, 3-7, 10-11, 13, 16-17, 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. 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 6-7. Issued claims 5, 8, and 10-12 provide the limitations of instant claims 5, 8, 11, and 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.
With respect to the double patenting rejections set forth above, applicant’s 3/2/2026 response acknowledges these rejections and provides no arguments.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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