DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 16-32 are pending.
Priority
Instant application 18/707,187, filed 05/03/2024 claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from IDS(s) received 05/03/2024 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 16-25 in the reply filed on 06/23/2026 is acknowledged. Applicant’s election without traverse of the species CD3-403 in the reply is also acknowledged. The elected species has the structure:
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Examination will begin with the elected species. In accordance with MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and applicable art was identified. Therefore, the entire scope of claims 16-25 has not yet been examined in accordance with Markush search practice. See MPEP 803.02.
Claims 26-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/23/2026.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed on Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
SPECIFIC DEFICIENCY - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
REQUIRED RESPONSE – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
SPECIFIC DEFICIENCY - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
REQUIRED RESPONSE - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 4, lines 10-11 and page 13, line 29 of the specification filed 11/04/2024.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claim 20 is objected to because of the following informalities:
Claim 20 recites a typographical error. In line 2, the phrase “is a β2-AR antagonist has a
permeability” should read “is a β2-AR antagonist having a permeability”.
Claim 21 is objected to because of the following informalities:
Claim 21 recite typographical errors. In line 5, the word “decease” should read “decrease”. In line 4, the phrase “and/or by or any” should read “and/or by
Claim 23 is objected to because of the following informalities:
Claim 23 recites a typographical error. In lines 1-2, the phrase “wherein the CD3 compound is in that it has characterised in at least one of” should read “wherein the CD3 compound is by at least one of”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 17-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Claims 17-20 are directed to a genus of β2-AR antagonists defined by functional properties: “non-bioavailable” (claim 17), “orally non-bioavailable” (claim 18), “minimal permeability through biological membranes” (claim 19), “a permeability through biological membranes that is no more than…as determined in a Caco2 cell or other intestinal permeability assay” (claim 20). Claim 21 recites a genus of “a non-bioavailable derivative of ICI 118,551…modified…by at least one of the addition of a hydrophilic group, the addition of a bulky group and the elimination of a hydrophobic group and/or by any other modification that is known by a person skilled in the art to decrease oral bioavailability.” Claim 22 recites a “CD3 compound,” further characterized in claim 23 by recited results (having an “IC50 < 100, 50, 20, or 10 nM”; “lacking toxicity”; and “being soluble”). Claim 24 recites three named compounds “or a derivative” thereof. In each case the claim is defined by what the β2-AR antagonist does or is called rather than by a disclosed structure shown to achieve the recited result.
To satisfy the written description requirement, the specification must demonstrate that the inventor was in possession of the claimed subject matter as of the filing date, by disclosing either a representative number of species falling within the genus or structural features common to the members of the genus such that one can visualize or recognize the members of the genus. See MPEP 2163. Possession of a genus defined by function is shown by disclosing species sufficient to support the functionally-defined genus, or a correlation between the recited function and a disclosed structure.
Claims 17-24 are directed to genera defined by function (“non-bioavailable β2-AR agonist”), property (“having minimal permeability”, “lacking toxicity”, “being soluble”), or proprietary designation (“CD3 compound”) rather than by structure. Claim 21’s “any other modification…known…to decrease oral bioavailability”, claims 22-23’s “CD3 compound”, and claim 24’s “derivative[s] of” the named compounds are an open-ended or undefined class of compounds. A generic statement of a desired property does not itself convey possession of the genus that achieves that property.
For the method of treatment claims, the specification reduces to practice a single compound, CD3-403, in a single experiment in which rats received an oral glucose bolus with or without CD3-403 and a reduced rise in blood glucose was observed (Specification page 9, lines 29-32 to page 10, lines 1-20). Caco-2 cell permeability data is provided only for CD3-403 (Specification, page 41, Supplementary Table 2). No other member of any claimed genus is shown to have been tested for the property of “non-bioavailability”, and no working example is directed to obesity. No “derivatives” of CD3 compounds of claim 31 are exemplified.
The specification and figures disclose individual, fully-specified drawn structures for a limited number of compounds (CD3-403, CD3-T1/T3, and additional lettered compounds appearing in the structure-activity section, e.g. “A-Z, ALPHA, BETA, GAMMA,”) reported with their inhibitory activity and/or toxicity. The disclosure contains no generic (Markush) structure, no common core or scaffold, and no partial structure defining the members of any claimed genus. Disclosure of the individual structures of a set of species, absent a common structural feature, does not describe the genus.
The specification discloses no correlation between structure and the recited function. The only structural teaching directed to the claimed property is that CD3-403 was obtained from ICI 118,551 “modified by addition of a hydrophilic group and elimination of a hydrophobic group to ensure minimal permeability through biological membranes” (Specification, page 10, lines 1-3). That description applies to a single molecule and does not identify which structural features, applied to the diverse class of β2-AR antagonists generally, render a compound non-bioavailable while preserving β2-AR antagonism. The section titled “Structural activity relationship (SAR) for CD3 compounds” (Specification pages 44-61) sets forth an assay protocol and IC50, Ki, and toxicity data for individual compounds, but discloses no structure-activity relationship correlating structural features to the recited properties (non-bioavailability, low permeability across biological membranes, decreased oral bioavailability) across a genus.
The prior art establishes that whether a given β2-AR antagonist is in fact “non-bioavailable” is not readily predictable, and that low membrane permeability does not establish non-bioavailability. See YANG (Molecular Pharmaceutics, vol. 4, no. 4, Aug. 2007, pp. 608–14). Yang states at page 608 (abstract) that “[s]otalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%,” and explains at page 612 that “[s]otalol is nearly completely absorbed after oral administration…[a]s a result, its absolute bioavailability is 90-100%.” Yang further reports (Table 3, page 611) that the lowest-permeability β-blockers tested nonetheless exhibit substantial absorption (e.g., nadolol and atenolol), and notes at page 614 that drugs in this “low permeability-high solubility group have an extent of absorption between 35 and 70%.”
The disclosed species are not representative of, and do not define, the vast genera claimed: all non-bioavailable β2-AR antagonists (claims 17-20), all ICI 118,551 derivatives reachable by “any other modification…known…to decrease oral bioavailability” (claim 21); all “CD3 compounds” (claims 22-23); and all “derivative[s]” of the named CD3 compounds (claim 24). The named species bear no disclosed common structural feature that would allow one of ordinary skill to recognize the remaining, undisclosed members of any of these genera.
Accordingly, the disclosure does not demonstrate that the inventor was in possession of the full scope of the claimed genus, and claims 17-24 fail to comply with the written description requirement.
Enablement
Claims 17-24 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 treating at least one of diabetes and obesity with the specific CD3 compounds CD3-403 (CIM-031403), CD3-T1 (CIM-012783_03_01), and CD3-T3 (CIM-121256_01_01), does not reasonably provide enablement for the full breadth of the functionally defined genus in claims 17-21. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), enablement is assessed under the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims:
The claimed compound genus “non-bioavailable β2-adrenergic receptor antagonist” is broad and functionally defined.
Nature of the invention:
The invention relates to a method of treating obesity or diabetes by administration of a non-bioavailable β2-adrenergic receptor antagonist.
State of the prior art and predictability in the art:
The prior art establishes that whether a given β2-AR antagonist is in fact “non-bioavailable” is not readily predictable, and that low membrane permeability does not establish non-bioavailability. See YANG (Molecular Pharmaceutics, vol. 4, no. 4, Aug. 2007, pp. 608–14). Yang states at page 608 (abstract) that “[s]otalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%,” and explains at page 612 that “[s]otalol is nearly completely absorbed after oral administration…[a]s a result, its absolute bioavailability is 90-100%.” Yang further reports (Table 3, page 611) that the lowest-permeability β-blockers tested nonetheless exhibit substantial absorption (e.g., nadolol and atenolol), and notes at page 614 that drugs in this “low permeability-high solubility group have an extent of absorption between 35 and 70%.”
The prior art thus provides no general means of arriving at, or verifying, non-bioavailable β2-AR antagonists across the claimed genus.
Level of ordinary skill in the art:
The person of ordinary skill is a person with advanced training in medicinal chemistry and/or pharmacology. This is a high level of skill, but it does not eliminate the unpredictability of identifying β2-AR antagonists which are non-bioavailable, nor which modifications yield non-bioavailability while retaining antagonism.
The amount of direction provided:
The specification describes a way to reduce sugar uptake from the gut by blocking the β2-adrenergic receptor (β2-AR) on enterocytes. The specification proposes that blocking this receptor with a non-bioavailable antagonist can reduce the post-meal rise in blood glucose. The guidance for which β2-AR antagonists are “non-bioavailable” is limited to the specific named compounds. The specification provides no common scaffold and no structure-function correlation to direct the person of ordinary skill toward “non-bioavailable” β2-AR antagonists.
Existence of working examples:
For the method of treatment, there is one working example, directed to a single compound (CD3-403) in a single acute glucose-tolerance experiment in rats. There is no working example for any other member of any claimed genus and no example directed to obesity.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. Low permeability does not reliably yield non-bioavailability, and the specification supplies neither a general method for arriving at non-bioavailable β2-AR antagonists across the genus nor a representative set of such compounds. Therefore, one of ordinary skill seeking to practice the full scope of claims 17-24 would be required to synthesize and empirically test numerous candidate antagonists and derivatives thereof to determine which achieve “non-bioavailability” while retaining β2-AR antagonism. This constitutes undue experimentation. Claims 17-24 are therefore rejected for failing to comply with the enablement requirement.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 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 20 recites that the non-bioavailable β2-AR antagonist “has a permeability through biological membranes that is no more than 2, 1.5, 1.2, 1.0, 0.5, 0.4, 0.2, or 0.1 cm/s, as determined in a Caco-2 cell or other intestinal permeability assay.” The metes and bounds of the claim cannot be determined for at least the following reasons:
First, the recited numerical limits (2, 1.5, 1.2, etc.) are inconsistent with the recited unit (cm/s). Apparent permeability coefficients (Papp) obtained in a Caco-2 assay are conventionally on the order of 10-6 cm/s. For example, see YANG et al (Molecular Pharmaceutics, vol. 4, no. 4, Aug. 2007, pp. 608–14). And the specification itself expresses the permeability of the disclosed compounds in units of x 10-6 cm/s (Specification, page 41, Supplementary Table 2). A threshold of “no more than…0.1 cm/s” therefore exceeds any physically observed Caco-2 permeability by several orders of magnitude, and one of ordinary skill cannot ascertain with reasonable certainty whether the recited values are intended to carry a factor of 10-6 or to be given their literal magnitude.
Second, the claim permits permeability to be “determined in a Caco-2 cell or other intestinal permeability assay” without specifying the assay or its conditions. Different assays can yield materially different permeability values for the same compound, such that whether a given antagonist meets the recited threshold depends upon (a) which assay is selected, and upon (b) whether that assay reliably reflects intestinal permeability at all. For example, the β2-AR antagonist sotalol has been reported to exhibit low apparent permeability in the Caco-2 assay (~ 24-fold lower than metoprolol) yet is nearly completely absorbed in humans, with an oral bioavailability of 90-100% (Yang, Table 3). A compound may therefore satisfy the recited Caco-2 permeability threshold while being highly bioavailable, and whether a given antagonist falls within the claim would depend on which assay is chosen and whether is result corresponds to actual intestinal permeability. The boundary of the claim thus varies with the measurement method, rendering the scope indefinite.
Claim 21 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.
The term “bulky group” in claim 21 is a relative term which renders the claim indefinite. The term “bulky group” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The steric bulk of a substituent is relative. Relative to a hydrogen atom, a methyl group is “bulky”. Relative to a methyl group, a tert-butyl group is “bulky”. Is replacing a hydrogen atom with a methyl group considered an “addition of a bulky group”? Or only if the hydrogen atom is replaced with a tert-butyl group?
Claims 22-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 22 recites “wherein the β2-AR antagonist is a CD3 compound”. The specification
Provides no definition for the term “CD3 compound”. There is no recited class membership criteria, and no common structural scaffold or Markush core for “CD3 compound”. “CD3” functions purely as a proprietary label attached to specific molecules in the specification. A skilled artisan reading claim 23 cannot determine what makes a compound a “CD3 compound”.
When a claim uses a term that is defined only by reference to undisclosed proprietary criteria, the boundary is not reasonably certain. If applicant intends to claim a list of compounds disclosed in the specification which are labeled with the prefix “CD3”, they should recite the list of compounds by name in the claim to make the intended claim scope clear. Otherwise, it is unclear what compounds are encompassed by the term “CD3 compound”.
Claim 23 recites the limitation “the CD3 compound” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 23 depends from claim 16 and neither claim provides antecedent basis for the limitation “the CD3 compound”. Additionally, claim 23 inherits the same issues identified above in claim 22 for its recitation of “CD3 compound”. Moreover, claim 23 presents additional issues:
The phrase “lacking toxicity” is a relative term which renders the claim indefinite. The phrase “lacking toxicity” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
“Toxicity” is a matter of degree that depends on, for example, dose, exposure, cell type or organism, endpoint, and assay. “Lacking toxicity” states no threshold and identifies no reference standard. The specification supplies no criterion defining when a compound “lacks toxicity”.
Similarly, the phrase “being soluble” is a relative term which renders the claim indefinite. Solubility is a matter of degree measured against, for example, a solvent, concentration, temperature, and pH. The limitation “being soluble” recites no threshold or conditions. It does not inform the skilled artisan how soluble, or under what conditions, a compound must be to satisfy the limitation.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 16-25 are rejected under 35 U.S.C. 103 as being unpatentable over TISDALE (US 20130143797 A1; published 2013) in view of SABIO (Bioorganic & Medicinal Chemistry Letters, vol. 18, no. 20, Oct. 2008, pp. 5391–95).
Tisdale teaches formulations for ameliorating symptoms of obesity and diabetes by administering Zn-α2-glycoproteins or a functional fragment thereof, alone or in combination with additional agents, β adrenergin receptor antagonists (title, abstract). In particular, Tisdale teaches that ([0203]):
“In one embodiment involving the treatment of obesity or diabetes in which it is desired to activate the β-3AR mechanism to achieve the desired lipolysis, glucose consumption, insulin sensitization, protein synthesis, increased energy expenditure, and the like. In this circumstance with some subjects it may be observed that the administered ZAG, or more likely the β-3AR agonist will exhibit some undesired activity at one or more of the β-1AR or the β-2AR, causing side effects or diminishment of desired efficacy. This circumstance would then call for the additional administration of β-AR antagonists, sometimes referred to as “classic beta blockers” so as to prevent the undesired activity at the β-1AR or β-2AR. These β-AR antagonists would preferably, but not necessarily, be selected to block the receptor subtype (one of β-1AR, β-2AR) that is associated with the side effect or mitigation of efficacy.
Tisdale therefore provides a motivation for administering a β-2AR antagonist to subjects having obesity or diabetes. Tisdale teaches that a variety of β-2AR antagonists are suitable ([0198]): Examples of β-AR antagonists that may be used in the present invention include, but are not limited to: propranolol, (−)-propranolol, (+)-propranolol, practolol, (−)-practolol, (+)-practolol, CGP-20712A, ICI-118551, (−)-buprranolol, acebutolol, atenolol, betaxolol, bisoprolol, esmolol, nebivolol, metoprolol, acebutolol, carteolol, penbutolol, pindolol, carvedilol, labetalol, levobunolol, metipranolol, nadolol, sotalol, and timolol. Any of these compounds read on claim 16’s generic recitation of a “β-2AR antagonist”.
Tisdale does not disclose the elected species compound CD3-403.
However, CD3-403 was known in the prior art as a β-2AR antagonist. Sabio discloses CD3-403 as β-2AR antagonist (see page 5394, “Compound 8”, 23.5 nM):
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Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) 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. See MPEP 2143.
Examples of 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.
Applying KSR example rationale (B) and/or (G), it would have been prima facie obvious to substitute the known β-2AR antagonists taught by Tisdale with the known compound CD3-403 in Tisdale’s method of treating obesity or diabetes. Aperson having ordinary skill in the art would have enjoyed a reasonable expectation of success that administering the β-2AR antagonist CD3-403 would be capable of blocking β-2AR that is associated with the side effect or mitigation of efficacy in obesity or diabetes subjects treated with ZAG and a β-3AR agonist.
The elected species CD3-403 reads on and renders obvious claims 16-25 because the compound necessarily possesses the recited properties relating to non-bioavailability.
With respect to the specific identify of the diabetes recited in claim 25, Tisdale teaches the two primary types of diabetes, Type I, and Type II (Tisdale, [0008]-[0009]). It would have therefore been prima facie obvious to administer CD3-403 to subjects having Type I or Type II diabetes.
Conclusion
Claims 16-25 are rejected. Claims 26-32 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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