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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Information Disclosure Statement
The information disclosure statement filed 13 March, 2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because one of the references was illegible. While the other citations have been considered, that citation was not.
Election/Restrictions
Applicant’s election of treating type 2 diabetes with (Ac-Lys-Lys)Lys-desPro38 exendin-4 in the reply filed on 30 Dec, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicants have elected (Ac-Lys-Lys)Lys-desPro38 exendin-4 to treat type 2 diabetes. A search was conducted for this invention, and references rendering it obvious were found. As a result, claims 68-78, 80, and 83-87 were examined, and claims 79, 81, and 82 were withdrawn from consideration. Applicants state that they believe claims 84 and 85 don’t read on their elected species, but those claims allow for functional variants of the exendin derivatives, which allow for the elected species.
During examination, a reference was found that anticipated at least one non-elected species. That reference is described below.
Claims Status
Claims 68-87 are pending.
Claims 68-87 are new
Claims 79, 81, and 82 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 30 Dec, 2025.
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.
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.
Claim 87 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating type 2 diabetes, reducing inflammation, and reducing appetite (and associated effects, such as lowering blood glucose, for example), does not reasonably provide enablement for treating infections or for all inflammatory or metabolic conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The MPEP states “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue.’ These factors include, but are not limited to: 1) the breadth of the claims; 2) the nature of the invention; 3) the state of the prior art; 4) the level of one of ordinary skill; 5) the level of predictability in the art; 6) the amount of direction provided by the inventor; 7) the existence of working examples; and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure” (MPEP 2164.01(a).
1 and 2) the breadth of the claims and the nature of the invention: The claim is drawn to a GLP-1 agonist to treat a variety of disorders, including inflammatory conditions, infections, and metabolic conditions.
3) the state of the prior art: Bendotti et al (Pharmacol. Res. (2022) 182 I06320) al discuss the effects of GLP-1 agonists (title). These compounds reduce levels of inflammation, which reduces activation of macrophages (2nd page, 2nd column, 2nd paragraph).
Zubair et al (StatPearls description of inflammation, 2024) state that inflammation facilitates wound healing and infection control (1st page, 1st paragraph). In other words, inflammation is a natural response to certain insults, including infection, and assist in healing these disorders.
Mullur et al (Physiol. Rev. (2014) 94 p355-382) discusses thyroid hormone regulation of metabolism. Thyroid hormones regulate metabolic processes and metabolism (p355, 1st column, 1st paragraph). GLP-1 regulation is downstream of these effects (p369, 1st column, 1st paragraph, continues to p370, 2nd column, 2nd paragraph), indicating that GLP-1 will not have a major effect on dysregulated metabolism due to thyroid problems.
4) the level of one of ordinary skill: The level of one of skill in the art is high.
5) the level of predictability in the art: GLP-1 agonists have been extensively studied, leading to at least a moderate level of predictability.
6 and 7) the amount of direction provided by the inventor and the existence of working examples: Applicants provide a bit more detail, such as additional inflammatory conditions (p39, 2nd paragraph, continues to p41, 1st paragraph), but this is merely a list of disorders, with no explanation of how the claimed compounds will benefit these disorders.
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: GLP-1 reduces inflammation, which will provide a benefit when inflammation is inappropriate or counterproductive. But, as noted by Zubair et al, inflammation plays a role in normal healing from injury and infection, and would reasonably be expected that reducing inflammation would be counterproductive in those cases. While GLP-1 analogs have been used to treat metabolic syndrome, this is much narrower than a metabolic condition, which includes such disorders as hyperparathyroidism, which, as suggested by Mullur et al, would not benefit from treatment by GLP-1 analogs. Thus, it will take undue experimentation to use the invention commensurate with the claims.
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.
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 68-78, 80, and 83-87 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.
The rejected claims all allow for functional variants of the specified exendin-4 derivatives. Functional variant is defined as retaining the function of the non-variant or original sequence, at least to some extent (p32, 3d paragraph). However, the sequences described by applicants have more than one function; they reduce inflammation, reduce blood glucose levels, and are cleaved by proteases, among other functions. Note that the definition does not limit the functional variant to polypeptides. If a compound has some of the functions of the explicitly described sequences, but not others, it is not clear if the claim limitation of functional variant has been met.
Claim Rejections - 35 USC § 112(d)
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.
Claims 83-85 are 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. The rejected claims describe specific exendin-4 analogs and “functional variants thereof,” which are allowed by claim 68, from which they depend. However, the specific analogs described in these claims are all functional variants of each other and of all the sequences of claim 68, so they do not further limit. 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.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 68-78 and 83-86 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boesen (US 20150297671, cited by applicants) with evidentiary support from Ding et al (Hepatology (2006) 43(1) p173-181).
Boesen discusses peptide analogs with branched amino acid probes (title). These can alter the inherent effect of the peptide, for example, increasing affinity (paragraph 9). Examples are given of GLP-1 analogs modified at the C-terminus with (Ac-Lys-Lys)Lys (paragraphs 351, 352, 376). Note, as evidenced by Ding et al, the exendin analogs applicants explicitly describe in their claim are GLP-1 receptor agonists (title), so would reasonably be considered functional variants.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 68-78, 80, and 83-87 are rejected under 35 U.S.C. 103 as being unpatentable over Larson et al (US 20110245165) in view of Boesen (US 20150297671, cited by applicants).
Larson et al discuss GLP-1 agonists (title). A most preferred embodiment is des Pro36 exendin-4(1-39) (paragraphs 72 and 73). Note that exendin 4 has prolines at positions 36, 38, and 38 (note SEQ ID 102 of Larson et al), so des Pro36 exendin 4(1-39) is identical to des Pro39 exendin 4(1-39), which is the base peptide of applicant’s elected species. Additional sequences may be attached to either the C-terminus or the N-terminus of these sequences (paragraph 61), with short oligolysine sequences used as examples (paragraphs 64 and 65). These compounds can be used to treat type 2 diabetes (paragraph 121), applicant’s elected disorder. Pharmaceutical compositions for injection are contemplated (paragraph 126).
The difference between this reference and the examined claims is that this reference does not discuss branched amino acid probes.
Boesen discusses peptide analogs with branched amino acid probes (title). These can alter the inherent effect of the peptide, for example, increasing affinity (paragraph 9), and can be placed on the N-terminus of the sequence (paragraph 12). An example is given of (Ac-Lys-Lys)Lys (paragraph 92), identical with applicant’s elected branched amino acid probe. Boesen describes embodiments where the probe is attached to exendin-4 and variants (paragraph 159). A number of examples are given where this probe is attached to the N-terminus of a polypeptide (paragraphs 317-331). Examples are given of GLP-1 analogs modified at the C-terminus (paragraphs 351, 352, 376). This reference discusses attaching branched amino acid probes to peptides.
Therefore, it would be obvious to attach a branched amino acid probe of Boesen, to modify the properties of the exendin analogs of Larson et al in a beneficial manner. As Boesen explicitly discusses modification of exendin 4 and variants, an artisan in this field would attempt this modification with a reasonable expectation of success.
Larson et al discuss des Pro36 exendin-4(1-39), identical to the base sequence of applicant’s elected species. Boesen discusses attaching (Ac-Lys-Lys)Lys to the N-terminus, generating applicant’s elected species and rendering obvious claims 68-78, 80, and 83-86.
Larson et al mentions treatment of type 2 diabetes, rendering obvious claim 87.
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.
first rejection
Claims 68-78, 80, and 83-87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 35, 43, and 49 of copending Application No. 17/470,310 (US 20220133839) in view of Larson et al (US 20110245165).
Competing claim 35 describes attachment of a branched peptide probe to the N or C terminus of a non-specified sequence. Competing claim 43 specifies that the starting residue be Lys or Orn, while competing claim 49 gives a Markush group of branch sequences, including Ac-Lys-Lys (combined with the Lys of the starting residue, this is applicant’s elected species).
The difference between the competing claims and the examined claims is that the competing claims do not specify the sequence it is attached to, or the utility of the material.
Larson et al discuss GLP-1 agonists (title). A most preferred embodiment is des Pro36 exendin-4(1-39) (paragraphs 72 and 73). Note that exendin 4 has prolines at positions 36, 38, and 38 (note SEQ ID 102 of Larson et al), so des Pro36 exendin 4(1-39) is identical to des Pro39 exendin 4(1-39), which is the base peptide of applicant’s elected species. Additional sequences may be attached to either the C-terminus or the N-terminus of these sequences (paragraph 61), with short oligolysine sequences used as examples (paragraphs 64 and 65). These compounds can be used to treat type 2 diabetes (paragraph 121), applicant’s elected disorder. Pharmaceutical compositions for injection are contemplated (paragraph 126).
Therefore, it would be obvious to attach the branched probes of the competing claims to the exendin analog of Larson et al, as a substitution of one element (the unspecified sequence of the competing claims) for another (the sequence of Larson et al) yielding expected results (a conjugate). As Larson et al discusses similar modifications, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
second rejection
Claims 68-78, 80, and 83-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, and 17 of U.S. Patent No. 11,141,455.
Competing claim 1 describes a peptide analog of exendin-4 (a functional variant of the exendin-4 variants of the examined claims) with a branched amino acid probe attached to the N or C terminus. Competing claim 4 lists a Markush group of probes, including (Ac-Lys-Lys)Lys, applicant’s elected probe. Competing claim 17 describes a method of treatment that overlaps with examined claim 87.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658