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 .
Any objection or rejection from the previous office action, which is not restated here, is withdrawn.
Disclaimer
Please note that the Examiner of Record for the present application has changed.
Election/Restrictions
Applicant’s election without traverse of Group II (i.e., claims 1, 64-70, 79-82, 90-93, and 95-97 drawn to a method of treatment comprising the compounds of claim 1) in the reply filed on June 20, 2022, is acknowledged. Additionally, Applicant’s election without traverse of SEQ ID NO: 23 as a single and specific peptide in the reply filed on June 20, 2022, is acknowledged.
Please note that the species election of a single and specific peptide is withdrawn in light of the previous Examiner’s examination of all the claims.
Status of Claims
Claims 1-97 were originally filed on March 24, 2021.
The amendment received on December 9, 2021, canceled claims 2-60, 62-63, 71-78, 83-89, and 94; and amended claims 1, 61, 64-65, 67-69, 79-82, 90-93, and 95-97. The amendment received on June 20, 2022, canceled claim 2. The amendment received on November 29, 2022, amended claims 1, 64-70, 79-82, 90-93, and 95-97; and added new claims 98-110. The amendment received on April 12, 2023, amended claim 1; and added new claims 111-144. The amendment received on October 18, 2023, amended claims 1, 97, 111-113, 115-117, 123-124, and 129; and added new claims 145-148. The amendment received on May 29, 2025, amended claims 1 and 145.
Claims 1, 64-70, 79-82, 90-93, and 95-148 are currently pending and under consideration.
Priority
The present application claims status as a 371 (National Stage) of PCT/JP2019/038827 filed September 24, 2019, and claims priority under 119(e) to U.S. Provisional Application No. 62/735,510 filed on September 24, 2018.
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 1, with respect to “treating”, it is noted that the instant specification defines “treatment” in the context of treating emesis by administering at least one of the GIP receptor agonist peptides disclosed, includes both prophylactic treatment and the treatment of emesis after a subject experiences emesis (See instant, [0410]). Prophylactic treatment includes administration of a GIP receptor agonist peptide before a subject experiences emesis, as well as administration of the GIP receptor agonist peptide before the subject is exposed to a substance, agent, or event, or before the subject contracts a condition, which results in or is likely to result in the subject experiencing emesis (See instant, [0410]). Treatment is also broadly defined as referring to clinical intervention in an attempt to alter the natural course of the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology (See instant, [0256]). Desirable effects of treatment include, preventing occurrence or recurrence of a condition, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the condition or treatment, preventing emesis, i.e., by preventing the occurrence of symptoms in whole or in part associated with a condition or side-effects known to accompany a specific treatment, decreasing the rate of progression, amelioration or palliation of the symptoms associated with emesis, and remission or improved prognosis (See instant, [0256]). Thus, the scope of claim 1 encompasses where emesis is prophylactically treated such that emesis is 100% prevented from occurring or treatment once the subject experiences emesis.
With respect to a “therapeutically effective amount”, it is noted that the instant specification defines “therapeutically effective amount” as an amount sufficient to elicit the desired biological response (See instant, [0410]). Thus, the claimed GIP receptor agonist peptide is administered to a subject in an amount sufficient to prophylactically treat or treat emesis in the subject. However, this amount is not limited.
With respect to “emesis”, it is noted that the instant specification does not define what is encompassed by the term “emesis”. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. Emesis is defined as an act or instance of vomiting (Merriam-Webster Dictionary, “Emesis”, available online at https://www.merriam-webster.com/dictionary/emesis, 7 pages (accessed on 11/5/25) at pg. 1). As such, emesis and vomiting are being interpreted interchangeably.
Sequence Interpretation
For claim 1, please note that the Examiner is interpreting the scope of the claim as open-ended requiring 100% identity to formula (II) and the subsequent Markush group of peptides with any N- and/or C-terminal additions.
For claim 130, please note that the Examiner is interpreting the scope of the claim as closed-ended requiring 100% identity and the same length to SEQ ID NO: 23.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The disclosure is objected to because of the following informalities: paragraphs [0018]-[0019], [0026]-[0028], [0279]-[0280], [0287]-[0289], [0333], [0335], [0343], [0346]-[0347], [0353]-[0359], [0497], and Table 1, depict amino acid sequences 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. Additionally, please update the Sequence Listing, if necessary. Appropriate correction is required.
Claim Objections
Claims 1 and 145 are objected to because of the following informalities: claims 1 and 145 recite, “…a GIP receptor agonist peptide,…” Although, the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The Examiner respectfully requests that Applicant uses glucose-dependent insulinotropic polypeptide (GIP) receptor agonist peptide for the first recitation, thereafter GIP receptor agonist peptide may be utilized. Appropriate correction is required.
Claims 1 and 145 are objected to because of the following informalities: claims 1 and 145 recite, “…gGlu, (gGlu)2, (gGlu)3, (gGlu)2-PEG…” Although, the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The Examiner respectfully requests that claims 1 and 145 recite, “γGlu, (γGlu)2, (γGlu)3, (γGlu)2-PEG…” in order to be consistent with the specification. Appropriate correction is required.
Claims 1 and 145 are objected to because of the following informalities: claims 1 and 145 recite, “…-GGGGG-, -GGGGGG-,…-GGGG-, -GGGGG-….” 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. Furthermore, it is noted that -GGGGG- is recited twice, and thus, only need to be recited once. Additionally, please update the Sequence Listing, if necessary.
Claims 1 and 145 are objected to because of the following informalities: claims 1 and 145 recite, “…wherein -L- represents -GGGGG- or -GGGGGG-, (PEG3)2,…PEG(3), or PEG3…” It is respectfully requested that claims 1 and 145 recite, “…wherein -L- represents -GGGGG-, -GGGGGG-, (PEG3)2,…PEG(3), or PEG3…” in order to be grammatically correct. Appropriate correction is required.
Claims 69 and 148 are objected to because of the following informalities: the claims recite “wherein the vomiting or the nausea is caused by one or more conditions or causes selected from the group consisting of: (1) a disease accompanied by vomiting or nausea; (2) vomiting and/or nausea induced by a chemotherapeutic drug including one or more of: an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine,….or a cannabis and cannabinoid product;…" It is respectfully requested that claims 69 and 148 recite, “wherein the vomiting or the nausea is caused by one or more conditions or causes selected from the group consisting of: (1) a disease accompanied by vomiting or nausea; (2) vomiting and/or nausea induced by a chemotherapeutic drug including one or more of: an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine,….a cannabis and cannabinoid product;…" See MPEP § 2173.05(h). Appropriate correction is required.
Claim 90 is objected to because of the following informalities: the claim recites “wherein the chemotherapeutic drug comprises: (i) an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine,….or a cannabis and cannabinoid product;…" It is respectfully requested that claim 69 recites, “wherein the chemotherapeutic drug comprises: (i) an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine,….a cannabis and cannabinoid product;…" See MPEP § 2173.05(h). Appropriate correction is required.
Improper Markush Grouping
Claims 69, 90, 98-110, and 148 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush grouping of a chemotherapeutic drug (i.e., claims 69 and 148) or a chemotherapeutic agent (i.e., claim 90) comprising an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine, hydroxyurea, azacytidine, irinotecan, interferon alpha, interleukin-2, oxaliplatin, carboplatin, nedaplatin, and miriplatin; an opioid analgesic; a dopamine receptor D1D2 agonist; or a cannabis and cannabinoid product is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons. A chemotherapeutic drug (i.e., claims 69 and 148) or a chemotherapeutic agent (i.e., claim 90) comprising an alkylating agent; a cytotoxic antibiotic; an antimetabolic agent; a vinca alkaloid; a chemotherapeutic agent selected from the group consisting of cisplatin, procarbazine, hydroxyurea, azacytidine, irinotecan, interferon alpha, interleukin-2, oxaliplatin, carboplatin, nedaplatin, and miriplatin; or a dopamine receptor D1D2 agonist is proper without recitation of an opioid analgesic, a cannabis or cannabinoid product. It is noted that an opioid analgesic, a cannabis and/or cannabinoid product do not function as a chemotherapeutic drug or chemotherapeutic agent. For example, the American Cancer Society teaches that cannabis does not treat or cure cancer (See American Cancer Society, “Possible Benefits of Cannabis for People with Cancer,” available online at https://www.cancer.org/cancer/supportive-care/integrative-medicine/cannabis/benefits-of-cannabis.html, 8 pages (accessed on 11/5/25) at pg. 2). As such, a chemotherapeutic drug or chemotherapeutic agent that can be an opioid analgesic, a cannabis and/or cannabinoid product is improper because these agents do not share a single structural similarity or a common use with the other recited alternatives. Therefore, an opioid analgesic, a cannabis or cannabinoid product. It is noted that an opioid analgesic, a cannabis and/or cannabinoid product do not share both a substantial structural feature and common use that flows from the substantial structural feature.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148 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
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 where treatment does not encompass 100% prevention and where the emesis is caused by any disease or condition,
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4, 7-8, 12, 14, 19-20, 23, 28, and 36, where treatment is 100% prevention and where the emesis is caused by opioid analgesic; AND
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NO: 22, where treatment is 100% prevention and where the emesis is caused by any chemotherapeutic agent;
but does not reasonably provide enablement for:
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 11, 16-17, 21, 24, 26-27, 30-35, and 27 where treatment is 100% prevention and where the emesis is caused by any disease, condition, or induced by any therapeutic agents including PYY and Y2R agonists;
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 5-6, 11, 15-18, 21-22, 24-27, 29-35, and 37, where treatment is 100% prevention and where the emesis is caused by opioid analgesic; AND
the treatment of emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-21 and 23-37, where treatment is 100% prevention and where the emesis is caused by any chemotherapeutic agent.
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.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any 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 skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to Claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148 as follows:
The Breadth of the Claims and The Nature of the Invention
Although addressing that the subject is suffering from emesis or at risk of suffering from emesis in claims 1 and 145 by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37, Applicants provide limited evidence in the specification that a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 can prevent emesis. As discussed in the “Claim Interpretation” section supra, the instant specification defines “treatment” in the context of treating emesis by administering at least one of the GIP receptor agonist peptides disclosed, includes both prophylactic treatment and the treatment of emesis after a subject experiences emesis (See instant, [0410]). Prophylactic treatment includes administration of a GIP receptor agonist peptide before a subject experiences emesis, as well as administration of the GIP receptor agonist peptide before the subject is exposed to a substance, agent, or event, or before the subject contracts a condition, which results in or is likely to result in the subject experiencing emesis (See instant, [0410]). Treatment is also broadly defined as referring to clinical intervention in an attempt to alter the natural course of the individual being treated, and can be performed either for prophylaxis or during the course of clinical pathology (See instant, [0256]). Desirable effects of treatment include, preventing occurrence or recurrence of a condition, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the condition or treatment, preventing emesis, i.e., by preventing the occurrence of symptoms in whole or in part associated with a condition or side-effects known to accompany a specific treatment, decreasing the rate of progression, amelioration or palliation of the symptoms associated with emesis, and remission or improved prognosis (See instant, [0256]). As such, “treating” encompasses 100% prevention of emesis that is caused or induced by any disease, condition, therapeutic agent, etc., thereby encompassing emesis caused/induced by motion sickness, a bacterial or viral infection, pregnancy, vertigo, anxiety, and chemotherapeutic agents, etc. (See Chavoustie, CT, “What causes dizziness and vomiting,” Medical News Today, available online at https://www.medicalnewstoday.com/articles/322638#causes, 19 pages (2025): teaching 15 causes of dizziness and vomiting including anxiety, infections, diabetes, inner ear issues, liver problems, neurological health problems, migraine, motion sickness, cyclic vomiting syndrome, alcohol or drugs, poisoning, organ injury, pregnancy, stroke, and heart attack). Thus, the scope of claim 1 encompasses treating emesis such that emesis is 100% prevented and is caused and/or induced by any disease, condition, therapeutic agent, etc. Accordingly, claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148 are unduly broad with respect to preventing emesis caused and/or induced by any disease, condition, therapeutic agent, etc., by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37.
The State of the Prior Art
It is noted that there is currently no prior art that teaches administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 in order to prevent emesis.
The Level of Skill in the Art
Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for treatment of emesis in a subject where treatment encompasses 100% prevention and where emesis is caused and/or induced by any disease, condition, therapeutic agent, etc.
The Level of Predictability in the Art,
The Amount of Direction Provided by the Inventor,
The Presence or Absence of Working Examples, and
The Quantity of Experimentation Necessary
The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 to a subject at risk of suffering from emesis excluding the limited situations identified in the rejection heading), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
In the instant case, Applicants demonstrate that specific GIP receptor agonist peptides can 100% prevent emesis caused/induced by specific therapeutic agents. More specifically, Applicants demonstrate that emesis induced by morphine administration is 100% prevented only when SEQ ID NOs: 4, 7-8, 12, 14, 19-20, 23, 28, and 36 is administered (See instant Table 13). Moreover, Applicants demonstrate that SEQ ID NO: 22 was able to 100% prevent emesis caused by cisplatin administration (See instant Table 15). However, Applicants demonstrate that SEQ ID NOs: 5-6, 15, and 18 did not 100% prevent emesis induced by morphine administration (See instant Table 13), SEQ ID NO: 17 did not 100% prevent emesis induced by cisplatin administration (See instant Table 15), SEQ ID NOs: 20, 22, 29, and 30 did not 100% prevent emesis caused by Y2R agonist administration (See instant Tables 16-17). To exacerbate matters, even though SEQ ID NO: 20 100% prevented emesis induced by morphine administration, SEQ ID NO: 20 did not 100% prevent, but rather partially inhibited emesis caused/induced by cisplatin (i.e., a chemotherapeutic agent) (See instant Tables 15) or Y2R agonist administration (See instant Table 16). Similarly, even though SEQ ID NO: 22 100% prevented emesis induced by cisplatin administration, SEQ ID NO: 22 did not 100% prevent, but rather partially inhibited emesis caused/induced by Y2R agonist administration (See instant Table 17). As such, such data demonstrates that the cause/induction of the emesis and the GIP receptor agonist amino acid sequence are critical in determining whether the GIP receptor agonist peptide can 100% prevent the emesis. Thus, an ordinary skilled artisan cannot expect without undue experimentation that each of the claimed GIP receptor agonist peptides will 100% prevent emesis in a subject where the emesis is caused/induced by any condition, condition, therapeutic agent, etc. excluding the identified situations in the rejection heading. This is because an ordinary skilled artisan cannot extrapolate the positive data provided in the specification to extend to the full scope of the claimed methods. Without more experimentation demonstrating a core structure or sequence that each GIP receptor agonist must contain in order to 100% prevent a representative number of causes of the emesis, the level of unpredictability remains high. Therefore, it is unpredictable that SEQ ID NOs: 4-37 will prevent emesis in a subject other than the limited situations identified in the rejection heading.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to Claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in Claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148 would not be enabled by the written disclosure excluding that of treating emesis in a subject by administering a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 where treatment does not encompass 100% prevention and where the emesis is caused by any disease or condition, and excluding the identified situations where emesis is 100% prevented. Therefore, Claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148, are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to administer a therapeutically effective amount of a GIP receptor agonist peptide of SEQ ID NOs: 4-37 to a subject at risk of suffering from emesis excluding the identified situations in the rejection heading.
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 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-148 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 1 and 145 are directed to administering a therapeutically effective amount of a GIP receptor agonist peptide of formula II or (I), respectively, where at each occurrence (R) in (Lys(R)) represents X-L- where -L- and X represent a set of alternatives. However, each sequence identifier that contains a (Lys(R)) only represents a single and specific X-L- group in the Sequence Listing, and not the recited group of alternatives. As such, each SEQ ID NO: that contains a (Lys(R)) group is inconsistent with the described SEQ ID NO: in the Sequence Listing. For example, originally elected SEQ ID NO: 23 contains a (Lys(R)) group at position A17 where R is (ethylene glycol)2-C15 diacid in the Sequence Listing. As such, the R group of SEQ ID NO: 23 cannot represent -GABA-GGG-C8 acid as encompassed by the current scope of claims 1 and 145. Similar interpretation of claims 114, 118-122, 125-128, and 130-144 also applies. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the scope of the R group.
Please note that the Examiner is interpreting that the R group is as recited in claims 1 and 145 in order to advance prosecution. Also please note that claims 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, 130-144, and 146-148 are rejected by virtue of their dependency.
Claims 1, 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-144 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 directed to administering a GIP receptor agonist peptide having the formula (II): P1-A1-A2-A3-Gly-Thr-A6-A7-Ser-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-Trp-Leu-A27-A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-A40-A41-A42-A43-P2 where each variable residue represents specific residues, and wherein the GIP receptor agonist is selected from a Markush group of specific species of amino acid sequences. However, claim 1 recites that the A1 residue represents Tyr, Phe, D-Tyr, or bis-halo-Tyr, but none of the specific species in the Markush group contain Phe or bis-halo-Tyr at the A1 position. Similarly, the A11 residue represents Ser or A5c, but none of the specific species in the Markush group contain A5c at the A11 position. The residue at position A14 represents Met, Nle, or Leu, but none of the specific species in the Markush group contain Nle at the A14 position. The residue at position A16 represents Lys, Lys(R), or Ala, but none of the specific species in the Markush group contain Lys(R) at the A16 position. The residue at position A17 represents Ile, Lys, Lys(R), Glu, or Gln, but none of the specific species in the Markush group contain Lys at the A17 position. As such, it is unclear how these identified residue positions can represent a residue that is not contained in any of the specific species recited in the Markush group. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the residue at the identified positions.
Please note that the Examiner is interpreting the scope of claim 1 such that the identified position can only be residues contained within a specific species recited in the Markush group in order to advance prosecution. Also, please note that claims 64-70, 79-82, 90-93, 95-110, 114, 118-122, 125-128, and 130-144 are rejected by virtue of their dependency.
Claims 69, 98-104, and 148 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. Regarding claims 69 and 148, the phrase "such as" in alternatives (6) and (9) renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Please note that the Examiner is interpreting the scope of claims 69 and 148 such that the limitations following “such as” are separate, individual limitations recited in the Markush group in order to advance prosecution. Also please note that claims 98-104 are rejected by virtue of their dependency.
Claims 69, 98-104, and 148 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. Pursuant to MPEP 2173.05(h), [a] Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. Here, claims 69 and 148 recite a Markush group as “selected from the group consisting of: ….. (2) vomiting and/or nausea induced by a chemotherapeutic drug including….; (8) pregnancy including hyperemesis gravidarium;….” (emphasis added). Pursuant to MPEP 2111.03(I), “including” is synonymous with “comprising”. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention because it is unclear what other alternatives are intended to be encompassed by as conditions or causes that cause vomiting or nausea.
Please note that the Examiner is interpreting the scope of claims 69 and 148 such that alternative (2) recites, vomiting and/or nausea induced by a chemotherapeutic drug selected from the group consisting of….; (8) pregnancy or hyperemesis gravidarium;….” in order to advance prosecution. Also please note that claims 98-104 are rejected by virtue of their dependency.
Claim 95 is 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 95 recites the limitation "the disease-state" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Please note that the Examiner is interpreting the scope of claim 95 such that it recites “the emesis” in order to advance prosecution.
Claims 111-113, 115-117, 123-124, and 129 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. Each claim is dependent upon claim 45. However, claim 45 has been canceled. As such, each claim is dependent upon a rejected claim. Thus, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the claim upon which claims 111-113, 115-117, 123-124, and 129 should depend upon. Please note that these claims cannot be examined further as the dependency is not clear.
Claims 145-148 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 148 is directed to administering a GIP receptor agonist peptide having the formula (I): P1-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-A40-A41-A42-A43-P2 where each variable residue represents specific residues, and wherein the GIP receptor agonist is selected from a Markush group of specific species of amino acid sequences. However, claim 145 recites that the A2 residue represents Ala or Aib, but SEQ ID NOs: 5 and 16-17 contain D-Ala at the A2 position. As such, it is unclear how SEQ ID NOs: 5 and 16-17 can contain D-Ala when the A2 position cannot represent D-Ala. Moreover, the A3 residue represents Glu or Pro, but none of the specific species in the Markush group contain Pro at the A3 position. As such, it is unclear how this identified residue position can represent a residue that is not contained in any of the specific species recited in the Markush group. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to the residues at the identified positions.
Please note that the Examiner is interpreting the scope of claim 145 such that the identified positions can only be residues contained within a specific species recited in the Markush group in order to advance prosecution. Also, please note that claims 146-148 are rejected by virtue of their dependency.
Claim Rejections - 35 USC § 112
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 65-66, 69, 98-104, and 146-148 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. Claims 65 and 146 are directed to where the emesis comprise nausea and/or vomiting. However, as discussed in the “Claim Interpretation” section supra, emesis and vomiting are interchangeable terms since emesis is defined as the act or presence of vomiting. Thus, claims 65 and 146 encompass an embodiment, i.e., emesis comprises vomiting, that does not further limit the scope of claims 1 and 145, respectively, which are directed to treating emesis. 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.
Please note that the Examiner is interpretating the scope of claims 65 and 146 such that the limitations are met if the limitations of claims 1 and 146 are met, respectively, in order to advance prosecution. Also, please note that claims 66, 69, 98-104, and 147-148 are rejected by virtue of their dependency.
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).
Claims 1, 64-65, 67, 69, 81, 82, 91-93, 95-98, 114, and 118-119 are rejected under 35 U.S.C. 103 as being unpatentable over Levy et al. WO 2006/086769 A2 published on August 17, 2006, in view of Maule WF. Nausea and Vomiting. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 84. Available from: https://www.ncbi.nlm.nih.gov/books/NBK410/.
For claims 1, 64, 67, 69, 91, 98, 114, 118-119, and 145, with respect to the GIP receptor agonist peptide, Levy teaches GIP analog and GIP-containing hybrid polypeptides with selectable properties where the hybrid polypeptides (See Levy, [0002]). Specific GIP analog polypeptide sequences include instant SEQ ID NOs: 7 and 14-15. Instant SEQ ID NO: 7 is depicted in the Table in [0084], second to last sequence, and Figure 12A, compound 060GIP3842. Instant SEQ ID NO: 14 is depicted in [00250] and Figure 12B as compound 0601GIP3794. Instant SEQ ID NO: 15 is depicted in [00309], last sequence, and Figure 12B, compound 0601GIP3979, where the C-terminus can be amidated (See Levy, [00343]). Thus, the teachings of Levy teach specific species of GIP analogs and GIP hybrid polypeptides comprising the amino acid sequences of instant SEQ ID NOs: 7 and 14-15 as recited in instant claims 1, 114, and 118-119.
With respect to administering a therapeutically effective amount, Levy teaches that that the GIP analogs, GIP hybrids, and GIPR agonists find use, when administered at therapeutically effective amounts, either in monotherapy or in adjunct therapy, in treating the diseases and conditions discussed (See Levy [00365]). As discussed supra in the “Claim Interpretation” section, the instant specification defines “therapeutically effective amount” as an amount sufficient to elicit the desired biological response (See instant, [0410]). Since the instant therapeutically effective amount is not limited, the general discussion of administering a therapeutically effective amount of Levy satisfies the instant claim limitations with respect to administering a therapeutically effective amount of the GIPR agonist as recited in instant claim 1 and with respect to where the peptide is administered as a monotherapy as recited in instant claim 64.
With respect to being administered to a subject to treat emesis, Levy teaches that GIP lacks the gastric emptying effect of GLP-1 that is a possible contributing factor to the incidence of nausea during GLP-1 treatment and which limits the peptide’s therapeutic window (See Levy, [00368], [00470]). Thus, it should permit the use of higher GIP dosing regiments (See Levy, [00368], [00470]). GIP compounds display a desired positive inotropic effect (See Levy, [00407]). Issues with available inotropic agents illustrates the need for therapies that are inotropic, with rapid onset of action, with prolonged duration of action (including a persistent effect, with absence of tachyphylaxis), with low toxicity (a high ratio of toxic to therapeutic dose), with absent or low nausea effect, and with a convenient (non-intravenous) route of administration (See Levy, [00408]). GIP compounds can provide these benefits (See Levy, [00408]). Further beneficial action of GIP compounds arises from a lack of or reduced anorectic effect and an absence of or relatively insignificant nausea effect, which can be important in the patient population to be treated (See Levy, [00409]). Levy also teaches methods for treating critically ill patients that would find benefit from anti- or non-catabolic therapy (See Levy, [00410]). The absence of or decreased anorexigenic effects, the absence of or decreased nausea and/or the absence of or reduction of weight loss, with or without the improvement in body composition, are advantageous in patients experiencing catabolic effects such as critically ill patients (See Levy, [00417]).
Moreover, Levy teaches that the compounds can be administered in a therapeutically effective amount to treat conditions/disorders such as diabetes of any kind, metabolic syndrome, cardiovascular conditions/disease, and cancer (See Levy, [00373]). As such, the subject encompasses one who has T2D as recited in instant claim 91. Cardiovascular conditions/disease include myocardial ischemia (i.e., myocardial infarction) and hypertension (See Levy, [00374]). The compounds also can be useful in treating other conditions associated with obesity include stroke and cancer, e.g., endometrial, breast, prostate