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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/15/2025 has been entered.
Claim Objections Withdrawn
The objection to claim 9, outlined in the previous Office Action, has been overcome by inventor’s amendment. The amendment corrects the claim text as appropriate.
112 Rejections Withdrawn
The rejections of claims 1, 2 and 6-9 under 35 USC 112(b) or 35 USC 112 (pre-AIA ), second paragraph, outlined in the previous Office Action, have been overcome by inventor’s amendment. With respect to claim 1, the amendment clarifies the claim as appropriate. With respect to the remaining claims (indefinite from indefinite), the rejection is moot.
Claim Rejections - 35 USC § 103, MAINTAINED
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1, 2 and 6-9 remain rejected, essentially for reasons of record, under 35 U.S.C. 103 as being unpatentable over US 10,308,634 B2, prior art of record. Inventor’s amendment and arguments have been carefully considered but are not persuasive.
Inventor teaches a method for the treatment of (a) acute lung injury and (b) acute respiratory distress syndrome comprising orally administering the IRAK4 inhibitor of formula I, wherein (a) or (b) is caused by direct lung injury which is caused by diffuse lung infection, bacteria, virus, toxin or hypoxia, and mediated by a cytokine combination of eosinophils, neutrophils and lymphocytes, and the treatment method is targeting lung pathological conditions selected from the group consisting of alveolar congestion, hemorrhage, neutrophil infiltration into airspaces or vascular wall, and alveolar wall thickening and hyaline membrane formation (claim 1). Dependent claim 2 (from claim 1) teaches that the direct lung injury is caused by bacteria. Dependent claim 6 (from claim 1) teaches that the disease is an LPS-induced disease. Dependent claim 7 (from claim 6) teaches that the drug is administered before LPS induction. Dependent claim 8 (from claim 7) teaches administration again after LPS induction. Dependent claim 9 (from claim 1) teaches that the compound is administered in the form of a drug which comprises a prophylactic and/or therapeutically effective amount of the compound of formula I and pharmaceutically acceptable carriers, diluents or excipients.
US 10,308,634 B2 teaches a method for the treatment of inter alia acute respiratory distress syndrome and acute lung injury by administering a pharmaceutical composition of an inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4) (abstract; column 3, line 46; column 1, line 30). The instant compound of formula I is one such exemplified IRAK4 inhibitor (column 59, Example 20). The pathogenesis of the pulmonary disorders, such as acute respiratory distress syndrome and acute lung injury, may be impacted by either infectious or non-infectious processes (column 3, line 50). Administration may be in any suitable manner such as oral, parenteral, etc. (column 23, line 13).
As previous stated, inventor principally distinguishes over the cited prior art by describing the lung injury or acute respiratory distress syndrome in terms of the type or cause of injury (“…wherein the acute lung injury or the acute respiratory distress syndrome is caused by direct lung injury, and the direct lung injury is lung injury caused by diffuse lung infection, bacteria, [etc.]…”), the mediating cytokines (“…a combination of TNFα, IL-6 and IL-1β…”) and inflammatory cells (“…eosinophils, neutrophils and lymphocytes…”), and the desired results (“…is targeting lung pathological conditions selected from the group consisting of: alveolar congestion, hemorrhage, [etc.]…”). However, the actual method steps of the prior art (i.e. administering a compound of formula I) and the reason for undertaking those steps (i.e. for treatment of inter alia acute respiratory distress syndrome or acute lung injury) are identical to those of the instant invention. Note that an obviousness rejection is proper when the prior art suggest a reason or provides motivation to make the claimed invention, even where the reason or motivation is based on a different motivation from that of applicant. It is not necessary in order to establish a prima facie case of obviousness that there be a suggestion or expectation from the prior art that the claimed invention will have the same or similar utility as the one newly discovered by applicant. (See MPEP 2144 (IV).) Furthermore, note that a chemical composition and its properties are inseparable. Products of identical chemical composition cannot have mutually exclusive properties. Thus, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. (MPEP 2112.01 (II).)
Furthermore, it is well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches to a person of ordinary skill in the art. (Note the discussion at MPEP 2141.02, VI.) The method of US 10,308,643 B2 is clearly intended to be a broadly applicable and generally useful approach to treatment, and it explicitly encompasses both the instant compound of formula I and the treatment of acute respiratory distress syndrome and acute lung injury - both infectious and non-infectious.
Finally, note that claim language that merely states a problem to be solved or a result obtained (“…is targeting lung pathological conditions selected from the group consisting of: alveolar congestion, hemorrhage, [etc.]…”), without setting forth well-defined boundaries of the claimed scope (i.e. by not specifying any way to achieve the desired results), is unclear. Typically no patentable distinction (no limit on the claim scope) is made by a recitation of an intended use or result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. Note the discussion at MPEP 2173.05(g).
Claims 6-8 are included in this rejection because administration before LPS-induction, or again after LPS-induction, would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention. Given the explicit teachings of US 10,308,634 B2 recognizing that infection may, or may not, accompany the pulmonary condition, one of ordinary skill, a highly skilled individual such as a clinical physician, would have been motivated, and with a reasonable expectation of success, to administer the compound of US 10,308,634 B2 (i.e. the instant compound), in the treatment protocol of US 10,308,634 B2, prior to LPS induction (i.e. prior to an LPS-induced inflammatory response) and certainly after LPS-induction (i.e. after a bacterial infection). One of ordinary skill would have been motivated to do so because the patient may well benefit from a modulated response (since, as has been well-known in the art for some time, the body’s inflammatory response itself can cause or exacerbate tissue injury).
Inventor argues that while the cited art discloses IRAK4 inhibitors and broadly suggests their potential use in treating all diseases associated with multiple inflammatory receptor pathways, such as TLR, IL-1R, IL-18R, IL-33R and IL-36R, that the reference provides no experimental data or pharmacological evidence to support such a sweeping assertion. Inventor concludes that the teachings of the cited art are very general and that this generalization is technically flawed and lacks credibility. The examiner respectfully disagrees.
As noted above, it is well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches to a person of ordinary skill in the art. (Note the discussion at MPEP 2141.02, VI.). In fact, inventor is essentially arguing that the cited patent, US 10/308,634 B2, is inoperable. The examiner respectfully points out, however, that every US patent is presumed valid (note 35 USC 282) and that this presumption of validity includes the presumption of operability (MPEP 716.07). Inventor’s argument is spurious.
Inventor points out that virtually all diseases involve some degree of inflammation or immune activation during their pathogenesis and argues that this does not imply that inhibiting a single inflammatory signaling node, such as the IRAK4 pathway, will necessarily yield therapeutically meaningful efficacy in vivo. And the examiner is in perfect agreement with inventor that this is so. Inventor concludes that in the absence of any specific pharmacodynamic data, disease model validation or mechanistic rational, that the cited art is merely speculative and conclusory because it offers no foundation or reasonable expectation of success. The examiner respectfully disagrees.
As noted, it is well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches to a person of ordinary skill in the art. (Note the discussion at MPEP 2141.02, VI.). Inventor is essentially arguing that the cited patent, US 10/308,634 B2, is inoperable. The examiner respectfully points out, however, that every US patent is presumed valid (note 35 USC 282) and that this presumption of validity includes the presumption of operability (MPEP 716.07). Inventor’s argument is spurious.
Inventor further argues that the cited art’s reasoning rests upon an unproven and inaccurate assumption that all IRAK4 inhibitors are equally effective across all the claimed inflammation-related diseases and that the instant invention directly refutes this assumption experimentally. Inventor points out that certain IRK4 inhibitors which exhibit excellent in vitro potency showed no efficacy whatsoever in the corresponding in vivo model and that this is an unexpected result which underscores the limitations and inaccuracies of the cited art’s simplistic targe-inhibition-equals-therapy logic. The examiner respectfully disagrees.
As noted above, the method of US 10,308,643 B2 is clearly intended to be a broadly applicable and generally useful approach to treatment. One of ordinary skill, a highly skilled individual such as a clinical physician, would be more than well aware that different compounds, such as different IRAK4 inhibitors, would not exhibit identical efficacies, or pharmacological properties, be they in vitro or in vivo, or that the efficacy of a single inhibitor might differ between in vitro and in vivo experiments. This is not, however, an unexpected result. This is simply a fact of the biological sciences. Merely pointing out that there are differences – differences one of ordinary skill in the art would immediately recognize as intrinsically present (because the inhibitors’ chemical structures differ) – in a broad class of chemical compounds, IRAK4 inhibitors, is not an unexpected result and as such cannot be the basis of distinguishing the instant invention over the cited art.
Inventor further argues that the rejection is predicated upon improper hindsight reasoning, because it is a retrospective reconstruction based upon the technical effects disclosed in the present application, and selectively pieces together prior art references to match a known outcome. The examiner respectfully disagrees.
First, the examiner respectfully notes that the rejection is predicated upon a single reference. That is, there is no selective piecing together of prior art references to match a known outcome; there is only one reference. Secondly, the rejection is predicated simply upon what the prior art reference explicitly teaches. It is not improper hindsight reasoning to predicate a rejection upon the pertinent and explicit teachings of a prior art reference that may also be encompassed by a broader teaching in that same reference – and, in particular, for a compound explicitly exemplified in the cited art. Inventor’s argument is spurious.
Inventor further argues that the cited art neither discloses nor suggests any correlation between IRAK4 inhibition improvement in lung pathology, provides no evidence that IRAK4 inhibitors are effective in an acute lung injury/acute respiratory distress syndrome model, nor point to the unique efficacy of Formula I.
First, the examiner respectfully points out that there is no limitation in the instant claims with respect to improvement in lung pathology. Secondly, note that claim language that merely states a problem to be solved or a result obtained (“…is targeting lung pathological conditions selected from the group consisting of: alveolar congestion, hemorrhage, [etc.]…”), without setting forth well-defined boundaries of the claimed scope (i.e. by not specifying any way to achieve the desired results), is unclear. Typically, no patentable distinction (no limit on the claim scope) is made by a recitation of an intended use or result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. Note the discussion at MPEP 2173.05(g). The actual method steps of the prior art (i.e. administering, for instance orally, a compound of formula I) and the reason for undertaking those steps (i.e. for treatment of inter alia acute respiratory distress syndrome or acute lung injury) are identical to those of the instant invention. An obviousness rejection is proper when the prior art suggest a reason or provides motivation to make the claimed invention, even where the reason or motivation is based on a different motivation from that of applicant. It is not necessary in order to establish a prima facie case of obviousness that there be a suggestion or expectation from the prior art that the claimed invention will have the same or similar utility as the one newly discovered by applicant. (See MPEP 2144 (IV).) A chemical composition and its properties are inseparable. Products of identical chemical composition cannot have mutually exclusive properties. Thus, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. (MPEP 2112.01 (II).)
Inventor again argues that the instant invention demonstrates unexpected results and references examples and tables in the instant specification. The examiner respectfully disagrees.
As above, one of ordinary skill, a highly skilled individual such as a clinical physician, would be more than well aware that different compounds, such as different IRAK4 inhibitors, would not exhibit identical efficacies, or pharmacological properties, be they in vitro or in vivo, or that the efficacy of a single inhibitor might differ between in vitro and in vivo experiments. This is not, however, an unexpected result. This is simply a fact of the biological sciences. Merely pointing out that there are differences – differences one of ordinary skill in the art would immediately recognize as intrinsically present (because the inhibitors’ chemical structures differ) – in a broad class of chemical compounds, IRAK4 inhibitors, is not an unexpected result and as such cannot be the basis of distinguishing the instant invention over the cited art.
Inventor stresses that one of ordinary skill in the art would have had neither a reasonable motivation nor a reasonable expectation of success in selecting any particular IRAK4 inhibitor from the cited art for the treatment of acute lung injury or acute respiratory distress syndrome and that the disclosure of the cited art amounts only to a broad and unverified hypothesis and is fundamentally incomplete and unreliable. The examiner respectfully disagrees.
First, the examiner respectfully points out that the instant compound of formula I is, as noted above, an exemplified compound of the cited art. That is, the instant compound is a demonstrably preferred compound of the cited art. Inventor’s assertion that one of ordinary skill in the art would, essentially, not recognize this preferred compound as a preferred compound would require a willful misreading of the clear teaching of the cited art. Secondly, inventor is, again, essentially arguing that the cited patent, US 10/308,634 B2, is inoperable. The examiner respectfully points out, however, that every US patent is presumed valid (note 35 USC 282) and that this presumption of validity includes the presumption of operability (MPEP 716.07). Inventor’s argument is spurious.
Inventor further argues that oral administration distinguishes over the cited art. The examine respectfully disagrees.
The cited art explicitly teaches several modes of administration including oral administration (column 23, line 13). One of ordinary skill, before the effective filing date of the instant invention, would have found it obvious to choose an appropriate formulation for administration. One of ordinary skill, a highly skilled individual, and with a reasonable expectation of success, would have chosen an oral formulation, for instance, and with a reasonable expectation of success, guided by ordinary clinical considerations (ease of patient compliance, etc.).
Inventor concludes by arguing that the instant invention clearly focuses the technical effect of the invention on the actual repair or alleviation of lung tissue structure and function. And the examiner is in perfect agreement with inventor that it does. However, the examiner respectfully points out that such “focusing” on desired outcomes is irrelevant. Claim language that merely states a problem to be solved or a result obtained (“…is targeting lung pathological conditions selected from the group consisting of: alveolar congestion, hemorrhage, [etc.]…”), without setting forth well-defined boundaries of the claimed scope (i.e. by not specifying any way to achieve the desired results), is unclear. No patentable distinction (no limit on the claim scope) is made by a recitation of an intended use or result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. Note the discussion at MPEP 2173.05(g).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN J DAVIS whose telephone number is (571)272-0638. The examiner can normally be reached M-F 8:30-5:00 PM EST.
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/BRIAN J DAVIS/Primary Examiner, Art Unit 1614 12/17/2025
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