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 .
Election/Restrictions
Applicant’s election of Group II (i.e., claims 27-31 directed to a method for treating a patient having diabetes, obesity, or overweight with complications by administering to the patient a compound of formula I) in the reply filed on June 23, 2026, is acknowledged. Additionally, Applicant’s election of Species A (i.e., overweight with complications as a single and specific disease/disorder/condition and a uric acid level range of greater than 420 µmol/L as a single and specific uric acid level range); Species B (i.e., a dose of 2 mg at a frequency of weekly as a single and specific dosing regimen (note: Applicants did not specify a dosing schedule other than weekly); and Species C (i.e., a medicament comprising Formula I, tris(hydroxymethyl)aminomethane and mannitol as a single and specific medicament) in the reply filed on June 23, 2026, 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)).
Regarding new claim 32, it is noted that it is added to Group II. Thus, Group II encompasses claims 27-32.
Status of Claims
Claims 1-17 were originally filed on December 22, 2023.
The amendment received on August 21, 2024, canceled claims 1-5 and 12-17; amended claims 8-9 and 11; and added new claims 18-31. The amendment received on June 23, 2026, amended claim 27; and added new claim 32.
Claims 6-11 and 18-32 are currently pending and claim 27 is under consideration as claims 6-11 and 18-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 28-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 June 23, 2026.
Priority
The present application claims status as a 371 (National Stage) of PCT/CN2022/100878 filed June 23, 2022, and claims priority under 119(a)-(d) to Chinese Application No. 202110711050.0 filed on June 25, 2021.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Chinese Application No. 202110711050.0, which papers have been placed of record in the file. Please note that the Chinese application is NOT in English and therefore cannot be verified. Thus, Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216. Until an English language translation is received and verified, the effective filing date of the instant application is June 23, 2022.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on February 28, 2024; August 21, 2024; and June 23, 2026, are being considered by the examiner.
Please note that NPL document 5 cited in the IDS received on 8/21/24; and NPL document 6 (note: English abstract not provided as cited) cited in the IDS received on 2/28/24 have been crossed out and not considered because an English language abstract, translation, or statement of relevance has not been provided as required under 37 CFR 1.98.
Sequence Interpretation
For claim 27, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to a compound of formula (I) (i.e., SEQ ID NO: 1) with any N- and/or C-terminal additions. It is noted that the compound of formula (I) is referred to as mazdutide, which is an oxyntomodulin (OXM) analog (See instant, pg. 3, last paragraph).
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 27, please note that the claimed patient population to be treated is limited to a patient who has diabetes, obesity, or overweight with complications. However, what disease/condition/disorder to be treated in this patient population by administering a compound of formula (I) is NOT limited. As such, any disease/condition/disorder can be treated by administering a compound of formula (I) as long as the patient the compound is being administered is overweight with complications (i.e., Applicant’s elected patient population). It is further noted that there is no limit as to the complications associated with the patient being overweight. As such, the complication associated with being overweight can be any complication.
Specification
The disclosure is objected to because of the following informalities: on page 4, 2nd paragraph; and page 7, 1st paragraph, depict the structure of formula (I) without an accompanying SEQ ID NO. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence with at least 4 defined amino acids in length requires a sequence identifier. It is noted that SEQ ID NO: 1 corresponds to the amino acid sequence depicted in Formula (I), and thus, the specification need only be amended to include recitation of SEQ ID NO: 1 before or after the depiction of formula (I). Appropriate correction is required.
Claim Objections
Claim 27 is objected to because of the following informalities: claim 27 depicts the structure of formula (I) without an accompanying SEQ ID NO. Pursuant to MPEP 2422 and 37 CFR 1.821(a), any amino acid sequence with at least 4 defined amino acids in length requires a sequence identifier. It is noted that SEQ ID NO: 1 corresponds to the amino acid sequence depicted in Formula (I), and thus, claim 27 needs only be amended to include recitation of SEQ ID NO: 1 before or after the depiction of formula (I). Appropriate correction is required.
Claim 28 is objected to because of the following informalities: claim 28 recites, “…administered at at least one ascending dose…, and administered at at least one maintenance dose…” It is respectfully requested that claim 28 recites, “…administered at, at least one ascending dose…, and administered at, at least one maintenance dose…” in order to be grammatically correct. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 28 and 31 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 28 is directed to where the compound is administered at least one an ascending dose once weekly for four weeks, and at least one maintenance dose once weekly for four weeks, where the ascending dose is selected from about 2.0 mg and about 4.0 mg, and where the maintenance dose is selected from about 6.0 mg. Claim 31 is directed to where the compound is administered at a starting dose of 2.0 mg once weekly for four weeks, an ascending dose of 4.0 mg once weekly for four weeks, and followed by a dose of 6.0 once weekly for at least four weeks. However, each claim is individually dependent upon claim 27, which recites that the compound is administered at a dose of about 1.0 mg, 2.0 mg, 2.5 mg,… once weekly. As such, it is unclear how the dose recited in claim 27 corresponds to one of the doses in claims 28 or 31. In other words, is it unclear whether the dose in claim 27 is an ascending dose or a maintenance dose. Furthermore, it is unclear how the once weekly administration in claim 27 corresponds to the specific dosing regimen recited in claims 28 and 31, i.e., one dose for about four weeks and a second dose for about four weeks. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the correlation between the dose and frequency of dose in claim 27 with those in claims 28 and 31.
Please note that the Examiner is interpreting the scope of claims 28 and 31 such that claim 27 recites each dosing regimen in the alternative, i.e., where the compound is administered as recited in claim 27, in claim 28 OR claim 31 in order to advance prosecution.
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.
Claims 27-28 and 31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ji et al., EClinicalMedicine 39:8 pages (first available August 2021) (cited in the IDS received on 2/28/24), alone or as evidenced by, MedChemExpress, “Mazdutide,” available online at https://www.medchemexpress.com/mazdutide.html?srsltid=AfmBOoqia_zJxD_OV7iLP3qz8x2b61dkkbzlVRDU7xOlu0MYrW3v9Dju, 2 pages (accessed on 9/12/26).
Please note: As stated in the “Priority” section supra, the instant effective filing date is 6/23/22. Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Additionally and/or alternatively, it is noted that both instant inventors are authors of the Ji reference. However, the Ji reference has additional authors, and thus, constitutes prior art under 102(a)(1). Applicants can overcome the rejection by invoking one of the exceptions to 102(a)(1).
For claims 27-28 and 31, Ji et al. discloses administering IBI362 (LY3305677) to adults with overweight (BMI ≥ 24 kg/m2) accompanied by hyperphagia and/or at least one comorbidity (i.e., pre-diabetes, hypertension, dyslipidemia, fatty liver, weight-bearing arthralgia, dyspnea, or obstructive sleep apnea syndrome caused by obesity) as a complication or obesity (BMI ≥ 28 kg/m2) once weekly via subcutaneous injection (See Ji, abstract; pg. 2, col. 2, 2nd paragraph). As evidenced by MedChemExpress, mazdutide is also known as IBI362 or LY3305677 (See MedChemExpress, pg. 1, “Description” section). When comparing the sequence/structure of mazdutide with the compound of instant formula (I) (See MedChemExpress, pg. 1), there is 100% identity. As such, IBI362 administered by Ji et al. constitutes administering to a patient (i.e., adult) a compound of formula (I) where the adult has overweight with complications as recited in instant claim 27. Eligible participants were randomized 2:1 to receive once-weekly subcutaneous injection of IBI362 or placebo in each of the three ascending dose cohorts for 12 weeks with additional 8 weeks of safety follow-up (See Ji, abstract). The dose-escalation regimens were: 3.0 mg cohort (1.0 mg weeks 1-4; 2.0 mg weeks 5-8; 3.0 mg weeks 9-12); 4.5 mg cohort (1.5 mg weeks 1-4; 3.0 mg weeks 5-8; 4.5 mg weeks 9-12); and 6.0 mg cohort (2.0 mg weeks 1-4; 4.0 mg weeks 5-8; and 6.0 mg weeks 9-12) (See Ji, abstract; pg. 2, col. 2, last paragraph to pg. 3, col. 1, 1st paragraph). It is noted that the instant specification defines an ascending dose as a dose that is less than the maximum effective dose required in a patient (See instant, pg. 5, 7th paragraph). Plus, a maintenance dose is defined as a dose as the maximum effective dose required in a patient (See instant, pg. 5, 7th paragraph). As such, the 6.0 mg cohort constitutes where the compound of formula (I) is administered at a dose of about 2.0 mg once weekly as recited in instant claim 27; where the compound is administered at an ascending dose of 2.0 mg once weekly for four weeks, a second ascending dose of 4.0 mg once weekly for four weeks, and an maintenance dose of 6.0 mg once weekly for four weeks as recited in instant claim 28; and where the compound is administered at a starting dose of 2.0 mg once weekly for four weeks, an ascending dose of 4.0 mg once weekly for four weeks, and followed by a dose of 6.0 once weekly for at least four weeks as recited in instant claim 31. The overweight or obese adults who received mazdutide showed a body-lowering effect (See Ji, abstract) thereby constituting where the patient has been treated by the administration of a compound of instant formula (I) as recited in instant claim 27.
Furthermore, with respect to where the compound of formula (I) is administered with at least one pharmaceutically acceptable carrier, it is noted that Ji et al. does not expressly disclose that mazdutide is administered with at least one pharmaceutically acceptable carrier. However, as discussed supra, Ji et al. expressly discloses that mazdutide is administered via subcutaneous injection. As such, it must follow that mazdutide is mixed with at least one pharmaceutically acceptable carrier, e.g., saline or water, because there is no other way for mazdutide to be subcutaneously injected if not in a liquid form, which would require the presence of at least one pharmaceutically acceptable carrier. Thus, the disclosure of Ji necessarily satisfies the claim limitation with respect to at least one pharmaceutically acceptable carrier as recited in instant claim 27.
Accordingly, Ji’s disclosure anticipates instant claims 27-28 and 31.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. WO 2016/209707 A1 published on December 29, 2016 (cited in the IDS received on 8/21/24), alone or as evidenced by Scireq, “Obese Mice Study Proves to Use the Ideal Weight,” available online at https://www.scireq.com/obese-mice/, 5 pages (accessed on 9/14/26).
For claim 27, ‘707 teaches administering compound 2 (i.e., ‘707 SEQ ID NO: 6, which is a OXM analog) in an amount of 15 or 30 nmol/kg to DIO (diet-induced obese) mice every 3 days for 15 days via subcutaneous injection (i.e., twice weekly) where the treated group exhibited weight loss and body fat (See ‘707, pg. 55, last paragraph to pg. 56, 2nd paragraph). When comparing ‘707 compound 2 (See ‘707, pg. 31-32, Example 2) with the instant compound of formula (I), there is 100% identity. Converting 15 nmol/kg into mg equates to 0.0034 mg of compound 2 (i.e., MW of mazdutide is 4563.13 g/mol; (15 x 10-9 mol/kg x 4563.13 g/mol)/10-3 g/mg = 0.068447 mg/kg x (50 g/1000) = 0.0034 mg) (note: obese mice typically weight 50g or more as evidenced by scireg.com reference (See scireg.com reference, pg. 1, 1st paragraph)). Converting 30 nmol/kg into mg equates to 0.00685 mg of compound 2 (i.e., same formula but 30 x 10-9 mol/kg). As such, ‘707 a specific embodiment constituting a method of treating a patient having obesity by administering to the patient a compound of formula (I) as recited in instant claim 27.
With respect to treating a patient having overweight with complications, ‘707 teaches that uncontrolled diabetes leads to several conditions that impact morbidity and mortality of patients where the leading cause of death for diabetic patients is cardiovascular complications (See ‘707, pg. 1, 2nd paragraph). One of the main risk factors for type 2 diabetes is obesity (See ‘707, pg. 1, 2nd paragraph). The majority of type 2 diabetes patients (~90%) are overweight or obese (See ‘707, pg. 1, 2nd paragraph). ‘707 also teaches that it is documented that a decrease in body adiposity will lead to improvement in obesity-associated co-morbidities including hyperglycemia and cardiovascular events (See ‘707, pg. 1, 2nd paragraph). ‘707, thus, teaches that therapies effective in glucose control and weight reduction are needed for better disease management (See ‘707, pg. 1, 2nd paragraph). Moreover, ‘707 teaches that oxyntomodulin (OXM) has been shown to suppress appetite and inhibit food intake in humans (See ‘707, pg. 2, last paragraph). In a specific 4-week study with overweight and obese subjects, three times daily preprandial subcutaneous administration of OXM produced a weight loss of 2.3 kg compared with 0.5 kg in the placebo group (See ‘707, pg. 2, last paragraph). In another shorter study, OXM was shown to decrease caloric intake and increase activity-related energy expenditure in overweight and obese subjects (See ‘707, pg. 2, last paragraph). ‘707 sought to overcome challenges of using OXM including the need for more potent, stable, long-acting and/or well-tolerated compounds (See ‘707, pg. 3, 3rd paragraph) such as ‘707 compound 2. As such, ‘707 teaches effective treatments for diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH) (See ‘707, pg. 3, 3rd paragraph; pg. 25, last paragraph to pg. 26, 3rd paragraph). Therefore, ‘707 demonstrates a correlation between subjects who have diabetes, obesity, or are overweight and can have cardiovascular complications where a decrease in body adiposity will lead to improvement in obesity-associated co-morbidities including hyperglycemia and cardiovascular events. Thus, ‘707 teaches treating a patient having obesity or being overweight with complications as recited in instant claim 27.
With respect to where the compound of formula (I) is administered with at least one pharmaceutically acceptable carrier, It is noted that ‘707 does not expressly teach that compound 2 is administered with at least one pharmaceutically acceptable carrier. However, as discussed supra, ‘707 expressly teaches that compound 2 is administered via subcutaneous injection. As such, it must follow that compound 2 is mixed with at least one pharmaceutically acceptable carrier, e.g., saline or water, because there is no other way for compound 2 to be subcutaneously injected if not in a liquid form, which would require the presence of at least one pharmaceutically acceptable carrier.
Additionally and/or alternatively, ’77 teaches that the compounds typically will be administered parenterally such as subcutaneous injection (See ‘707, pg. 24, last paragraph). The compound is administered to the subject in conjunction with an acceptable pharmaceutical carrier, diluent, or excipient as part of a pharmaceutical composition for treating type 2 diabetes, obesity, NAFLD and/or NASH (See ‘707, pg. 24, last paragraph). The pharmaceutical composition can be a solution or a suspension such as in which a compound is complexed with a divalent metal cation such as zinc (See ‘707, pg. 24, last paragraph). The compound can be formulated in a solid formulation such as by lyophilization, which is then reconstituted in a suitable diluent solution prior to administration (See ‘707, pg. 24, last paragraph to pg. 25, 1st paragraph). Suitable pharmaceutical carriers for parenteral administration include mannitol, lactose, sucrose, sorbitol, phenol and m-cresol (See ‘707, pg. 25, 1st paragraph). Plus, in preparing the compounds including compound 2 to evaluate physical properties of the compounds such as solubility, the compound in dry powder form was diluted in 10 mM Tris and m-cresol (See ‘707, pg. 35, 2nd paragraph; pg. 36, 1st to 2nd paragraph). Thus, the teachings of ‘707 satisfy the claim limitation with respect to where the compound of instant formula (I) is administered with at least one pharmaceutically acceptable carrier where the carriers can be mannitol, Tris, and m-cresol as recited in instant claim 27.
With respect to where the compound of instant formula (I) is administered at a dose of about 2.0 mg once weekly, ‘707 teaches that dosages for once-weekly dosing can fall within the range of about 0.05 to about 30 mg per person per week (See ‘707, pg. 27, 3rd paragraph) thereby encompassing about 2.0 mg. Certain compounds can be dosed bi-weekly, once-weekly or monthly (See ‘707, pg. 27, 3rd paragraph). Therefore, the teachings of ‘707 with respect to the dosage overlap with the instantly claimed dose of about 2.0 mg as recited in instant claim 27; and the teachings of ‘707 satisfy the claim limitations with respect to where the compound of instant formula (I) is administered once weekly as recited in instant claim 27.
Regarding the dose, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%". The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.) Moreover, the Federal Circuit found that a prima facie case existed where a claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms and the prior art taught that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." In re Geisler, 116 F.3d 1465, 1469-82, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997). Therefore, the claimed dose of compound of instant formula (I) would have been obvious to one of ordinary skill in the art since the claimed dose (i.e., about 2.0 mg) lies within the prior art dose range of the compound of instant formula (I) (i.e., about 0.05 to about 30 mg per person per week).
Additionally and/or alternatively, regarding the dose and/or frequency of administration, the dose and/or frequency of administration of mazdutide are clearly result specific parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal dose of mazdutide and/or optimal frequency of administration of mazdutide needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the dose of mazdutide and/or frequency of administration, such as those taught by ‘707, for treating a patient having obesity or being overweight with complications, because an ordinary skilled artisan would have been able to utilize the teachings of ‘707 to obtain various dose and/or frequency of administration parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the dose and/or frequency of administration of mazdutide would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to administer a compound of instant formula (I) and at least one pharmaceutically acceptable carrier such as Tris, mannitol, and m-cresol in an amount of about 2.0 mg once weekly to a patient who is overweight with cardiovascular complications in order to reduce body weight and body fat. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because OXM analogs such as a compound of instant formula (I) were known to be administered in an amount ranging from about 0.05 to about 30 mg at a frequency of bi-weekly, once-weekly or monthly to a patient who is overweight with cardiovascular complications where such administration reduces body weight and body fat as taught by ‘707. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that a compound of instant formula (I) of ‘707 was administered to a patient in combination with a pharmaceutically acceptable carrier such as Tris, mannitol, and m-cresol, and therefore, administering the compound of instant formula (I) in an amount of about 2.0 mg once weekly to a patient who is overweight with cardiovascular complications would support the reduction of body weight and body fat by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claims 28 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. WO 2016/209707 A1 published on December 29, 2016 (cited in the IDS received on 8/21/24), alone or as evidenced by Scireq, “Obese Mice Study Proves to Use the Ideal Weight,” available online at https://www.scireq.com/obese-mice/, 5 pages (accessed on 9/14/26), and further in view of Thomas et al. WO 2023/235724 A1 published on December 7, 2023 (effective filing date of June 1, 2022) (cited in the IDS received on 8/21/24), OR Roberts et al. US 2024/0148879 A1 published on May 9, 2024 (effective filing date of February 21, 2021).
Regarding the use of ‘724, Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
For claims 28 and 31, with respect to the limitations incorporated from claim 27, please see discussion of ‘707 supra. Briefly, ‘707 teaches that mazdutide can be administered at a dose of about 0.05 to about 30 mg per person per week, and at a frequency of bi-weekly, once-weekly or monthly (See ‘707, pg. 27, 3rd paragraph). However, ‘707 does not expressly teach the specific dosing regimen as recited in instant claims 28 and 31.
When using ‘724 as the secondary reference
‘724 teaches doses and dosing regimens for a GLP-1/Gcg co-agonist that result in unexpectedly improved weight loss, improved body composition, robust glucose control, lipid lowering and/or insulin sensitization sparing beta-cell insulin secretory workload while at the same exhibiting only mild or moderate adverse events (See ‘724, pg. 3, 2nd paragraph). ‘724 teaches a method for treating a condition such as T2D, hyperglycemia, obesity, dyslipidemia, NAFLD, NASH, major adverse cardiac events (MACE), obstructive sleep apnea, osteoarthritis, reducing body weight, reducing food intake, and/or inducing satiety in a patient by administering a once weekly dose of SEQ ID NO: 1 to a patient in need thereof for at least about 2 weeks, and thereafter increasing the dose to greater than about 6 mg to about 16 mg and administering the increased dose to the patient once weekly for at least about 2 weeks (See ‘724, pg. 3, last paragraph to pg. 4, 2nd paragraph; pg. 12, 3rd to last paragraph) thereby constituting where the increased dose is an ascending or maintenance dose. When comparing ‘724 SEQ ID NO: 1 with the compound of instant formula (I), there is 100% identity. The once weekly dose in step (1) is about 1 mg to about 6 mg or about 2 mg (See ‘724, pg. 6, 3rd and 5th paragraph; pg. 15, 3rd and 5th paragraph; claim 9-11). ‘724 also teaches that the first dose and each subsequent increased dose are increased in increments of about 1.5 mg, about 2.0 mg, up to about 6.0 mg and wherein each dose is administered for at least about 2 weeks (See ‘724, pg. 6, last paragraph; pg. 15, last paragraph to pg. 16, 2nd paragraph; claim 12). Plus, ‘724 teaches that administering each dose once weekly for at least about 4 weeks (See ‘724, pg. 7, 3rd paragraph; claim 13 and 20). As such, ‘724 teaches that the first dose can be about 2.0 mg and each subsequent dose is increased over the previously administered dose in an increment of about 2.0 mg (i.e., about 4.0 mg total dose) (See ‘724, pg. 6, last paragraph to pg. 7, 1st paragraph; pg. 16, 2nd paragraph) thereby constituting a starting dose of about 2.0 mg and increased in an increment of about 2.0 mg (i.e., an ascending dose) where each of these doses are administered for at least about 4 weeks. In a specific embodiment, ‘724 teaches administering a first dose of about 2 mg once weekly for at least about 2 weeks, increasing the dose to about 4 mg once weekly for at least about 2 weeks, increasing the dose to about 6 mg once weekly for at least 2 weeks, increasing the dose to about 8 mg once weekly for at least about 2 weeks, and increasing the dose to about 10 mg once weekly for at least about 2 weeks (See ‘724, clam 15). Thus, ‘724 suggests administering the compound of instant formula (I) to a patient who is obese or overweight with complications in a dose and dosing regimen that overlaps with the instant dose and dosing regimen recited in claims 28 and 31.
Regarding the dose and/or frequency of administration, the dose and/or frequency of administration of mazdutide are clearly result specific parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal dose of mazdutide and/or optimal frequency of administration of mazdutide needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the dose of mazdutide and/or frequency of administration, such as those taught by ‘724, for treating a patient having obesity or being overweight with complications, because an ordinary skilled artisan would have been able to utilize the teachings of ‘724 to obtain various dose and/or frequency of administration parameters such as an starting dose of about 2 mg administered once weekly for about 4 weeks, then increasing the dose to about 4 mg once weekly for about 4 weeks, and finally increasing the dose to about 6 mg once weekly for about 4 weeks with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the dose and/or frequency of administration of mazdutide would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
When using ‘879 as the secondary reference
‘879 teaches peptides such as SEQ ID NO: 13/LY3305677 that can be administered to treat an underlying metabolic dysfunction that leads to NASH or that leads to obesity; or to treat diabetes or obesity; or to treat conditions associated with obesity such as arthritis, low back pain, breathing disorders such as asthma and obstructive sleep apnea thereby constituting complications (See ‘879, [0011]-[0012], [0024], [0043], [0120]-[0121]). It is noted that ‘879 cites ‘707 in reference to SEQ ID NO: 13 (See ‘879, [0024]) thereby constituting where ‘879 teaches a compound of instant formula (I). The peptide is formulated as a solution for injection comprising pharmaceutically acceptable excipients such as a buffering agent, an osmolarity adjusting agent, a stabilizing agent, a surfactant, a pH adjuster, a preservative and a solvent (See ‘879, [0097], [0110], [0112]). The osmolarity adjusting agent can be mannitol and the buffering agent can be Tris (See ‘879, [0097], [0112]). As such, ‘879 teaches a formulation comprising a compound of instant formula (I) in combination with Tris as a buffering agent and mannitol as an osmolarity adjusting agent. The peptide is administered parenterally, e.g., subcutaneously (See ‘879, [0112], [0123]). ‘879 also teaches that the therapeutically effective amount, frequency of administration, and length of treatment can depend on various factors including the nature and severity of the condition, the potency of the compound, the route of administration, the age, body weight, general health, gender and diet of the subject, etc. (See ‘879, [0123]). In some embodiments, ‘879 teaches that a peptide is administered parenterally in a dose from about 0.01 mg to 1 mg or 1-27 mg, over a period of about 1 week (See ‘879, [0123]). In other embodiments, ‘879 teaches that a peptide is administered parenterally in a dose of about 1-5 mg over a period of about 1 week (See ‘879, [0123]). The peptide can be administered in any suitable frequency for treatment disclosed, e.g., sc once a day, once a week, or once every two weeks (See ‘879, [0124]). In certain embodiments, the peptide is administered sc once a week (See ‘879, [0124], [0136]). The length of treatment can be determined by the treating physician (See ‘879, [0124]). In some embodiments, the peptide is administered chronically to treat a condition for at least about 2 months, 3 months, 6 months, etc. (See ‘879, [0124], [0136]). Moreover, ‘879 teaches that a pharmaceutical dosage formulation can be configured to administer between about 0.05 to about 20 mg per week, once weekly for up to 6 weeks, about 4 weeks or less; one per week for at least 4 weeks (i.e., one month) (See ‘879, [0131]-[0132]). Furthermore, ‘879 teaches that the method can comprise administering a first one or more doses (the treatment initiation phase) of a peptide, followed by subsequent second one or more and higher doses of the peptide, each of the first and second doses being administered for one or more weeks (See ‘879, [0134]) thereby constituting ascending and/or maintenance doses. The first dose(s) and second dose(s) can be followed by one or more third doses that be higher than the second dose(s) (See ‘879, [0134]) thereby constituting ascending and/or maintenance doses. Thus, the ‘879 teachings suggest adjusting/modifying doses that overlap with the instantly claimed doses and dosing regimen that overlap with the instantly claimed dosing regimen of mazdutide as recited in instant claims 28 and 31.
Regarding the dose and/or frequency of administration, the dose and/or frequency of administration of mazdutide are clearly result specific parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal dose of mazdutide and/or optimal frequency of administration of mazdutide needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to adjust the dose of mazdutide and/or frequency of administration, such as those taught by ‘879, for treating a patient having obesity or being overweight with complications, because an ordinary skilled artisan would have been able to utilize the teachings of ‘879 to obtain various dose and/or frequency of administration parameters such as an starting dose of about 2 mg administered once weekly for about 4 weeks, then increasing the dose to about 4 mg once weekly for about 4 weeks, and finally increasing the dose to about 6 mg once weekly for about 4 weeks with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the dose and/or frequency of administration of mazdutide would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
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 27-28 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 10-26 of copending Application No. 18/869,519 (US 2025/0296973 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘519 claims:
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(‘519, claims 1, 12-13, 16, 18, and 21-22). As such, the ‘519 claimed invention constitutes the instant method of treating a patient who is obese or overweight with complications by administering mazdutide to the patient in a dose of about 1.0 to about 10 mg once weekly as recited in instant claim 27. ‘519 also claims where the administration is by subcutaneous injection (See ‘519, claim 7). As such, the administration of mazdutide of ‘519 must be combined with a pharmaceutically acceptable carrier because there is no other way for compound 2 to be subcutaneously injected if not in a liquid form, which would require the presence of at least one pharmaceutically acceptable carrier. Thus, the ‘519 claimed invention anticipates instant claim 27.
With respect to instant claims 28 and 31, the three dosing cycles claimed by ‘519 are encompassed such that ‘519’s first and second dosing cycles constitute an ascending dose in instant claim 28, and constitutes a starting dose and an ascending dose as recited in instant claim 31. Moreover, it is noted that the instant specification teaches that “about”, when present in connection with a number, may refer to, for example, +/- 5%, etc. (See instant, pg. 6, 3rd paragraph). Such teaching does not constitute a definition, and thus, is not imparted into the claimed invention given the use of “may” and “for example”. Therefore, “about 3 mg” of mazdutide for ‘519’s first dosing cycle lies within the claimed range of about 2.0 mg to about 4.0 mg for an ascending dose for about 4 weeks as recited in instant claim 28, and is close to 2.0 mg once weekly for four weeks as recited in instant claim 31. “About 6.0 mg” for ‘519’s second dosing cycle is close to instant “about 4.0 mg” thereby suggestive of a second ascending dose for about 4 weeks as recited in instant claim 28, and is close to 4.0 mg once weekly for four weeks as recited in instant claim 31. Plus, “about 9 mg” of mazdutide for ‘519’s third dosing cycle is close to instant “about 6.0 mg” thereby suggestive of at least one maintenance dose for about 4 weeks as recited in instant claim 28, and is close to 6.0 mg once weekly for four weeks as recited in instant claim 31. A prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metal Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Court held a proper rejection of a claim directed toward an alloy of having "0.8% nickel, 0.3% molybdenum, 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium.) Therefore, the claimed dose amounts of mazdutide for the starting dose, ascending dose(s), and/or for the maintenance dose would have been suggested to one skilled in the art.
Accordingly, the ‘519 claimed invention is not patentably distinct from the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-28 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 19/525,396 (not yet published). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘396 claims:
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(See ‘396 claims 1-5, 11-12, and 16). ‘396 also claims where the method comprises administering an escalating dose of about 2 mg once weekly for about 4 weeks, a second escalating dose of about 4.0 mg once weekly for about 4 weeks, administering a maintenance dose of about 6 mg for at least 16 weeks, and optionally further wherein: 7) the treatment results in a reduction in body weight from baseline of the subject; or 18-19) the treatment results in reduction in systolic or diastolic blood pressure; or 21) the treatment results in a reduction on triglyceride from baseline of the subject (‘396, claim 18). The remaining ‘396 claims are encompassed by the instant method. Since ‘396 claims where the mazdutide administration reduces blood pressure and/or triglyceride levels and/or reduce body weight where the subject can be obese or overweight (i.e., BMI of at least 23 kg/m2), it would necessarily follow that the ‘396 method encompasses treating a patient who is obese or overweight with complications as recited in instant claim 27. Moreover, ‘396’s claimed invention anticipates the instant doses and dosing regimens as recited in instant claims 27-28 and 31. Thus, the ‘396 claimed invention is not patentably distinct from the instant invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-28 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of copending Application No. 19/525,402 (not yet published) in view of Chen et al. WO 2016/209707 A1 published on December 29, 2016 (cited in the IDS received on 8/21/24).
‘402 claims:
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(‘402, claims 1-9 and 11). As such, ‘402’s claimed method constitutes a method of treating a patient who is obese by administering a compound of instant formula (I) as recited in instant claim 27. The doses and dosing regimen claimed by ‘402 anticipates the instant doses and dosing regimen as recited in instant claims 27-28 and 31.
However, ‘402 does not expressly claim where mazdutide is administered with a pharmaceutically acceptable carrier and where the patient has complications as recited in instant claim 27. Please see discussion of ‘707 supra. Briefly, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer mazdutide subcutaneously in combination with a pharmaceutically acceptable carrier to a patient who is obese with cardiovascular complications because cardiovascular complications are known to be associated with obesity and because mazdutide is known to be administered subcutaneously in combination with a pharmaceutically acceptable carrier to a patient in need of treatment. Thus, the ’402 claimed invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
Prosecution Insights