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 .
DETAILED ACTION
This Office Action is in response to Applicant’s Arguments and Amendment filed, 09/17/2025, wherein the Amendment amended claims 1, 5-8, 10-18, cancelled claims 2-4, and 19-21, and added claims 22-27
Claims 1, 5-18, and 22-27 are pending.
Priority
This application claims the following priority:
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.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
In the 06/18/2025, Office Action, Groups I-III were rejoined, and examined. Group IV, claims 19-21, were withdrawn from consideration.
The 09/17/2025 Amendment to the claims deleted Group IV, claims 19-21.
Claims 1, 5-18, and 22-27 are examined on the merits herein.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Improper Multiple Dependents
Applicant’s amendments to claims 5-18 are sufficient to place these claims in proper dependent claim form.
Claim Objections
-Applicant’s amendment to claim 1 is sufficient to overcome this objection.
-Applicant’s deletion of claims 2-3 is sufficient to overcome these objections.
35 U.S.C. § 112(a)
Applicant’s deletion of “An agent for use in medicine” and “prodrugs or derivatives thereof,” is sufficient to overcome the Written Description rejection.
35 U.S.C. § 112(b)
Applicant’s deletion of claim 4 is sufficient to overcome this rejection.
REJECTIONS-MAINTAINED, MODIFIED, & NEW
Applicant’s amendment to independent claim 1, and amendment to claims 5-18, placing them in proper dependent form, have resulted in the below new and modified rejections.
Claim Interpretation
In claim 1, last line, the phrase “wherein each alkyl group is optionally substituted with a phenyl group or with one or more halogen atoms,” is interpreted as referencing “alkyl” in C1-C5(cyclo)alkyl, and as referencing “alk” in “C1-C5 (cyclo)alkoxy.”
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(New) Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 depends from Claim 1, wherein Claim 1 defines R as “one or more optional substituents on the aryl ring(s) selected from halogen, hydroxy, cyano, -CONH2, C1-C5(cyclo)alkyl or C1-C5 (cycloalkoxy), wherein each alkyl group is optionally substituted with a phenyl group or with one or more halogen atoms.”
However, claim 22 recites the following compounds,
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, wherein “R” is a C1 alkyl or an -O-Benzyl (-CH2C6H5), which is outside the scope of the definition of R in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)- Enablement
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.
(New) Claims 8-16 and 27 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Claim 8 is directed toward a method for treating or preventing any tissue damage in a subject having any inflammatory condition and/or any tissue damaging condition comprising administering to the subject a therapeutic amount of
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626
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As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
The prior art is silent regarding compounds of instant Formula (I), and thus is silent regarding methods of treating a single disease, let alone treating any tissue damage in a subject having any inflammatory condition or any tissue damaging condition, by administering a compound of Formula (I).
US 2003/0171251 to Pepys (IDS of 01/25/2024) teaches compounds for the treatment and prevention of tissue damage, wherein the compounds inhibit the binding of C-reactive protein to an autologous or extrinsic ligand (title, abstract), which is the same use taught for the compounds of instant formula (I). Pepys teaches these compounds as having the following formula:
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, which is structurally distinct from the instantly claimed compounds. While Pepys teaches its compounds for the treatment and prevention of tissue damage, it only provides evidence of treating tissue damage caused by a single condition, acute myocardial infarction ([0064]-[0080]). Pepys is silent regarding prevention of tissue damage.
Pepys (Targeting C-reactive protein for the treatment of cardiovascular disease, Nature, published 2006, IDS of 08/17/202) teaches that 1,6-bis(phosphocholine)-hexane,
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, is an inhibitor of CRP, wherein administration of this compound in rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP (pg. 1217). Thus, Pepys teaches a method of decreasing tissue damage in rats with a single condition, acute myocardial infarction. Pepys is silent regarding prevention of tissue damage.
Thus, while the prior art teaches species of bis(phosphocholine)ligands, compounds outside of the scope of instant Formula (I), for inhibition of CRP to treat tissue damage in patients with acute myocardial infarction, the prior art does not teach compounds for the treatment and/or prevention of tissue damage due to any inflammatory condition or any tissue damaging condition.
Predictability in the Art
Since the prior art does not teach compounds of instant Formula (I), and since the prior art teaches species of bis(phosphocholine)ligands as only treating tissue damage due to a single condition, i.e., acute myocardial infarction, the art of treating or preventing any type of tissue damage in a subject having any type of inflammatory and/or tissue damaging condition, is unpredictable.
Working Examples
The instant specification provides zero working examples of a method of treating or preventing tissue damage due to an inflammatory condition or tissue damaging condition, by administering a compound of instant Formula (I).
The instant specification only provides IC50 (µM) values for eleven exemplified species of formula (I) in MIRA immunoturbidimetric assays, wherein these assays are used to measure the efficacy and potency of complex formation between CRP (C-reactive protein) and the instantly exemplified compounds.
The eleven exemplified species and their IC50 values are as follows:
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1
0.6 µM
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132
314
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2
0.65 µM
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141
337
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3
1.22 µM
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143
328
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4
0.58 µM
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134
392
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5
0.73 µM
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132
363
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6
0.56 µM
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152
374
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7
0.51 µM
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137
333
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8
0.59 µM
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142
373
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9
0.55 µM
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364
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10
0.67 µM
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347
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11
1.2 µM
As can be seen in the above chart, the position of attachment of the aromatic ring to the amide bonds and the types and positions of the heteroatoms in the heteroaryl rings has a great impact on the IC50 value. See specifically the difference in IC50 values between a) compounds 1 and 11, which differ only in their position of attachment of the aryl ring to the amide group, and b) compounds 3 and 4 which differ only in their position of nitrogen in their heteroaryl rings.
In view of these differences, it is not possible to determine a structure-function relationship in the compounds of formula (I) that is critical to impart their usefulness in inhibiting CRP, let alone a structure-function relationship that is critical to impart their useful for treating and/or preventing tissue damage due to an inflammatory and/or tissue damaging condition.
Direction and Guidance
In view of a) the unpredictability in the art, b) the lack of working examples, and c) the lack of structure-function relationship among the species of Formula (I) that is critical to inhibit CRP in in vitro assays, let alone to treat and/or prevent tissue damage, the specification lacks sufficient direction and guidance to use the instantly claimed invention.
Quantity of Experimentation
The amount of experimentation required to determine which compounds of Formula (I) are effective to treat and/or prevent tissue damage in which inflammatory and/or tissue damaging conditions, would be astronomical, starting with proof-of-concept, and proceeding through all levels of lead identification and optimization. This amounts to invention, not development; it is an undue amount of experimentation.
For these reasons, claims 8-16 and 27 are not enabled.
Allowable Subject Matter
Claims 1, 5-7, 17-18, and 23-26 are allowable. The examiner has conducted a search and has not found relevant prior art that would meet the claims limitations.
REASONS FOR ALLOWANCE
The following is an examiner’s statement of reasons for allowance:
The instantly claimed compound is novel and non-obvious over the prior art.
The closest prior art is US 2007/0155738 to Steeneck (published 2007, PTO-892, claim 1), which teaches the following compound:
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(pg. 809, claim 1), and species such as
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and
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(pg. 964, 971, claims 95 and 96).
The reference does not teach a palindromic compound comprising quinuclidine rings and a carboxy group attached to the methylene group following the amide group, which are the distinct features of the instantly claimed compound.
Therefore, the prior art neither anticipates nor reasonably makes obvious the claimed
invention and therefore, the claimed invention is deemed novel and unobvious over the
prior art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.Q.W./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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