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 .
Application Status
2. Applicant's amendment and response, filed on February 12, 2026 has been reviewed by the examiner and entered of record in the file.
3. Claims 1 and 9 are amended. Claims 2 and 6 are canceled. Claims 20-26 are newly added.
4. Applicant previously elected the neurosteroid species: allopregnanolone. The non-elected species of neurosteroid remain withdrawn from consideration as directed to non-elected subject matter.
5. Claims 1, 3 4, 7-9 and 19-26 are under examination with the elected species and are the subject of this office action.
Priority
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
In this case, the disclosure of the prior-filed application, Provisional Application No. 62/674,379, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application, as follows:
the instantly recited limitation “wherein the TLR-mediated inflammatory condition is non-responsive to GABAergic drugs” in independent claims 1 and 20 lacks description or support in Provisional Application No. 62/674,379.
7. Therefore, the instant claims are afforded benefit of priority to PCT/US2019/ 033053, filed May 20, 2019.
Claim Objections
8. The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
It is noted that claim 21 is missing from the claim set. Thus, misnumbered claims 22-26 have been renumbered as claims 21-25.
9. Claim 7 is objected to for missing a period at the end of the claim.
Previous Claim Rejections - 35 USC § 112(b)
10. Claims 7-9 were previously 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.
11. Claim 7 was previously rejected as being indefinite (lacking antecedent basis) regarding the limitation "pain" because “pain” had been excluded from the subgenus of TLR-mediated inflammatory conditions recited in claim 1.
In view of Applicant’s amendment to delete the recitation of “pain” from claim 7, the indefiniteness rejection is withdrawn.
12. Claim 9 was previously rejected as lacking antecedent basis for the limitation of “decreased TLR signaling in the peripheral blood mononuclear cells or cerebrospinal fluid” in the claim, because there is no recitation of TLR signaling and/or peripheral blood mononuclear cells or cerebrospinal fluid in claim, and as being unclear how or when said step of decreased TLR signaling occurs.
In view of Applicant’s amendatory changes to the claim, the previous indefiniteness rejection is withdrawn.
Previous Claim Rejections - 35 USC § 102
13. Claims 1-4, 7 and 19 were previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rogawski et al., Epilepsia 2013.
14. In view of Applicant’s amendment to delete the inflammatory condition of seizure from claim 1, the previous anticipation rejection is withdrawn.
Previous Claim Rejections - 35 USC § 103
15. Claims 8 and 9 were previously rejected under 35 U.S.C. 103 as being unpatentable over Rogawski et al., Epilepsia 2013, as applied to claims 1-4, 7 and 19, and further in view of Iori et al., Neurobiology of Disease 2016, and Tanga et al., PNAS 2005.
16. In view of Applicant’s amendment to delete the inflammatory condition of seizure from claim 1, the previous anticipation rejection is withdrawn.
New Claim Rejections - 35 USC § 112(b)
17. 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.
18. Claims 1, 3, 4, 7-9 and 19-26 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.
19. Claim 1 is unclear in the following aspects:
(a) The limitation “wherein the inflammatory condition is non-responsive to GABAergic drugs,” renders the claim indefinite because the term “GABAergic drugs” is not defined by the claim nor in the Specification, such that one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
(b) It is not clear if the limitation that “the inflammatory condition is non-responsive to GABAergic drugs” previously occurred in the subject having the TLR-mediated inflammatory condition, or if it is an additional step subsequent to the administration of the neurosteroid in the subject, or if the property of being non-responsive refers to the TLR-mediated inflammatory condition itself and not the subject being treated. Clarification is requested.
20. Claims 3, 4, 7-9, 19 and 26 are rejected as being dependent upon and including all of the limitations of claim 1
21. Claim 9 depends from claim 8, and recites the limitation of “the peripheral blood mononuclear cells” in lines 4-5. However, there is insufficient antecedent basis for this limitation in the claim, because claim 8 is limited to assaying the sample of “peripheral blood,” not of “peripheral blood mononuclear cells.
**In view of a broadest reasonable interpretation of claim 9, the limitation of “peripheral blood mononuclear cells” is construed to mean “peripheral blood cells.”
22. Claim 20 is unclear in the following aspects:
(a) The limitation “wherein the alcoholism or alcohol detoxification is non-responsive to GABAergic drugs,” renders the claim indefinite because the term “GABAergic drugs” is not defined by the claim nor in the Specification, such that one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
(b) It is not clear if the limitation that “the alcoholism or alcohol detoxification is non-responsive to GABAergic drugs” previously occurred in the subject having alcoholism or alcohol detoxification or if it is an additional step subsequent to the administration of the neurosteroid in the subject, or if the property of being non-responsive refers to the condition of alcoholism or alcohol detoxification itself and not the subject being treated. Clarification is requested.
**In view of a broadest reasonable interpretation as understood by one of skill in the art, consistent with the specification, the limitation that the inflammatory condition/ alcoholism or alcohol detoxification “is non-responsive to GABAergic drugs” is construed to mean that the inflammatory condition/ alcoholism or alcohol detoxification does not demonstrate clinical benefit in general, and wherein “GABAergic drugs” encompass drugs that enhance the effects of gamma-aminobutyric acid (GABA), a neurotransmitter responsible for reducing neuronal excitability in the brain, including benzodiazepines, barbiturates, and certain anticonvulsants.
23. Claims 22-25 are rejected as being dependent upon and including all of the limitations of claim 20.
24. Claim 23 depends from claim 22, and recites the limitation of “the peripheral blood mononuclear cells” in lines 4-5. However, there is insufficient antecedent basis for this limitation in the claim, because claim 8 is limited to assaying the sample of “peripheral blood,” not of “peripheral blood mononuclear cells.
**In view of a broadest reasonable interpretation of claim 23, the limitation of “peripheral blood mononuclear cells” is construed to mean “peripheral blood cells.”
New Claim Rejections - 35 USC § 103
25. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
26. Claims 1, 3, 4, 7 and 26 are rejected under 35 U.S.C. 103(a) as being obvious over Chen et al., PLoS One (2011), in view of Nava-Mesa et al. and in view of Gambuzza et al., CNS & Neurological Disorders - Drug Targets, (2014).
This rejection is made as a result of Applicant’s amendments to the claims.
Claim 1 is directed to a method for treating a TLR-mediated inflammatory condition in a subject (more specifically, Alzheimer’s disease (claim 7)), comprising administering a neurosteroid to the subject having or suspected of having a TLR-mediated inflammatory condition, (wherein the neurosteroid is allopregnanolone (claim 26)), and
wherein the inflammatory condition is non-responsive to GABAergic drugs.
**In view of a broadest reasonable interpretation, the limitation that the inflammatory condition “is non-responsive to GABAergic drugs” is construed to mean that the inflammatory condition does not demonstrate clinical benefit in general, wherein “GABAergic drugs” encompass drugs that enhance the effects of gamma-aminobutyric acid (GABA), including benzodiazepines, barbiturates, and certain anticonvulsants.
Priority claim: it is noted that Provisional Application No. 62/674,379, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for the limitation “wherein the TLR-mediated inflammatory condition is non-responsive to GABAergic drugs” in claims 1 and 20. Therefore, the instant claims are afforded benefit of priority to PCT/US2019/ 033053, filed May 20, 2019.
27. Chen et al. teach the administration of allopregnanolone for the successful treatment of Alzheimer’s disease:
“[t]ogether these findings provide preclinical evidence for the optimal treatment regimen of APa [allopregnanolone] to achieve efficacy as a disease modifying therapeutic to promote regeneration while simultaneously decreasing the pathology associated with Alzheimer’s disease.”
(see Abstract),
28. Chen et al. do not teach wherein Alzheimer’s disease is nonresponsive to GABAergic drugs.
29. Yet, Nava-Mesa et al. teach that Alzheimer’s disease (AD) symptoms worsen in patients following administration of the GABAergic anticonvulsant valproate:
“chronic treatment with valproate was associated with significant toxic effects including morphological brain changes in patients with moderate AD (Tariot et al., 2011),”
(page 10, right column, second paragraph). Morphological brain changes in Alzheimer’s disease (AD) patients having been treated with a GABAergic drug meet the limitation of AD being nonresponsive, required by claim 1.
30. Thus, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to treat Alzheimer’s disease in a subject in need thereof comprising administering allopregnanolone to said subject, wherein Alzheimer’s disease is nonresponsive to a GABAergic drug, with a reasonable expectation of success.
31. Regarding the limitation in the preamble of claim 1, i.e., “a TLR-mediated inflammatory condition,” Gambuzza et al. teach the role of toll-like receptors (TLRs) in Alzheimer’s disease:
“[I]n AD, TLR signaling pathways may either mediate the uptake, playing a beneficial role, or induce the proinflammatory cytokine production, playing a detrimental role [14].”
(page 1543, first paragraph), and:
“Some of the classes of TLR antagonists developed could be used to limit a specific or excessive inflammatory response in late-stages of AD.”
(page 1550, left column, under “5.2. TLR Antagonists”).
Gambuzza et al. suggest TLR4 inhibition in particular as a target in the treatment of AD, wherein the TLR4 antagonist ibudilast has demonstrated anti-inflammatory activity in both peripheral immune systema and in the CNS via glial cell activation, i.e.:
“CNS-directed anti-inflammatory activity… can also be useful in AD treatment.” (page 1550, left column, last two paragraphs, and right column, second paragraph).
As such, claims 1, 7 and 26 are prima facie obvious.
Claim 3 is drawn to claim 1, and limits wherein the neurosteroid is an inhibitor of toll-like receptor signaling or corticotropin (CRF) releasing hormone signaling, (more specifically, TL4 receptor signaling (claim 4)).
32. Regarding the limitations describing the neurosteroid in claims 3 and 4, while Chen et al. do not teach the ability of allopregnanolone to inhibit toll-like receptor (TLR) signaling, this inherent property flows from the administration step itself. As subjects suffering the inflammatory condition of Alzheimer’s disease meet the criteria of a subject in need of allopregnanolone (i.e., an inhibitor of TLR), as taught by Gambuzza et al., the claim as a whole is obviated. MPEP § 2112 (II) states "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC S Calif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products. [emphasis added].
See MPEP 2112.01: Composition, Product, and Apparatus Claims [R-07.2015]
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I. PRODUCT AND APPARATUS CLAIMS — WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT
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Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).
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See also In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971) (Claim 1 was directed to a parachute canopy having concentric circumferential panels radially separated from each other by radially extending tie lines. The panels were separated "such that the critical velocity of each successively larger panel will be less than the critical velocity of the previous panel, whereby said parachute will sequentially open and thus gradually decelerate." The court found that the claim was anticipated by Menget. Menget taught a parachute having three circumferential panels separated by tie lines. The court upheld the rejection finding that applicant had failed to show that Menget did not possess the functional characteristics of the claims.); Northam Warren Corp. v. D. F. Newfield Co., 7 F. Supp. 773, 22 USPQ 313 (E.D.N.Y. 1934) (A patent to a pencil for cleaning fingernails was held invalid because a pencil of the same structure for writing was found in the prior art.).
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II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
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"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.").
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33. As such, by virtue of administering the neurosteroid allopregnanolone to a subject, one is necessarily administering an inhibitor of TLR2, TLR4 or TLR7.
Therefore, claims 3 and 4 are prima facie obvious.
34. Claims 8 and 9 are rejected under 35 U.S.C. 103(a) as being obvious over Chen et al., PLoS One (2011), in view of Nava-Mesa et al. and in view of Gambuzza et al., CNS & Neurological Disorders - Drug Targets, (2014), as applied to claims 1, 3, 4, 7 and 26, above, and further in view of Kandimalla et al., Nucleic Acids Research (2013).
This rejection is made as a result of Applicant’s amendments to the claims.
Claim 1 is addressed in detail, above.
Claim 8 is drawn to claim 1, further comprising assaying a sample from the subject for TLR signaling in peripheral blood or cerebrospinal fluid, wherein decreased TLR signaling is an indication of administration of a therapeutically effective amount of allopregnanolone.
Claim 9, as amended, is drawn to the method of claim 8, further comprising increasing the amount of allopregnanolone administered to the subject if decreased TLR signaling in the peripheral blood mononuclear cells or cerebrospinal fluid is not detected in the sample.
**In view of a broadest reasonable interpretation of claim 9, the limitation of “peripheral blood mononuclear cells” is construed to mean “peripheral blood cells.”
35. Chen et al. in view of Nava-Mesa et al. and in view of Gambuzza et al. suggest the treatment of Alzheimer’s disease in a subject in need thereof comprising administering allopregnanolone to said subject, wherein Alzheimer’s disease is nonresponsive to a GABAergic drug, but do not teach the step of assaying a sample from the subject for TLR signaling in peripheral blood or cerebrospinal fluid, wherein decreased TLR signaling is an indication of administration of a therapeutically effective amount of allopregnanolone.
36. Yet, Kanimalla et al. teach that following treatment with TLR antagonists in murine and primate subjects in vivo, a sample of peripheral blood obtained from said subjects was assayed, indicating that said TLR antagonists successfully inhibited TLR signaling pathways, i.e., TLR-mediated cytokine induction, (see abstract). Kanimalla et al. go on to teach that the extent and duration of TLR inhibition is dose-dependent upon the antagonist administered, i.e., TLR-mediated immune response increases as the dose amount of TLR antagonist is increased:
“The extent of inhibition of TLR7- and TLR9 mediated immune responses by the antagonist was dependent on the dose of antagonist compound administered and the type of cytokine induced by the TLR agonist (Figure 7A and B and Supplementary Figures S7 and S8). At the lowest dose of antagonist compound 1 (1mg/kg), a 30–55% inhibition of various cytokines induced by TLR7 and TLR9 agonists was observed. The extent of inhibition ranged from 55 to 80% at 5-mg/kg and 90 to 100% at 15-mg/kg dose of antagonist compound 1 for various cytokines induced by TLR7 and TLR9 agonists (Figure 7A and B and Supplementary Figures S7 and S8),”
(page 3955, right column, last paragraph- page 3956, left column, first paragraph, and Figure 7).
37. Thus, the step of assaying levels of TLR in a sample of a subject following treatment with a TLR antagonist does not render novel the known method of administering allopregnanolone to treat AD in a subject in need thereof. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention that assaying for the expression level of a protein that plays a key role in a given disease is beneficial towards improved and effective treatments, and the same applies to the features recited in claims 8-9 of the present application. Therefore, a method for treating a subject suffering from AD, comprising administering an effective amount of the TLR inhibitor allopregnanolone, followed by assaying a sample from said subject for decreased TLR signaling in peripheral blood or cerebrospinal fluid, and/or increasing the amount of allopregnanolone administered to the subject if decreased TLR signaling in the peripheral blood or cerebrospinal fluid is not detected in the sample, is not considered inventive. It would have been prima facie obvious to one skilled in the art to assay a sample of peripheral blood taken from a subject having been treated with a TLR antagonist, to measure resulting TLR expression levels in said sample, and if necessary, optimize the dose amount of said TLR antagonist, with a reasonable expectation of success.
Therefore, claims 8 and 9 are prima facie obvious.
38. Claims 1, 3, 4, 7, and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over Finn et al., Pharmacology and Therapeutics (2004), in view of Liu et al, PNAS (2011), regarding the limitation of treating alcoholism/ alcohol detoxification.
This rejection is made as a result of Applicant’s amendments to the claims.
Claim 1 is directed to a method for treating a TLR-mediated inflammatory condition in a subject (more specifically, alcohol detoxification (claim 7)), comprising administering to the subject a neurosteroid, (more specifically allopregnanolone),
and where the subject is female (claim 19)), and
wherein the TLR-mediated inflammatory condition is non-responsive to GABAergic drugs.
Claim 20 is drawn to a method for treating a TLR-mediated inflammatory condition in a subject wherein the TLR-mediated inflammatory condition is alcoholism or alcohol detoxification, comprising administering to the subject allopregnanolone (claim 25), and wherein the subject is female (claim 24),
wherein the inflammatory condition is non-responsive to GABAergic drugs.
Priority claim: it is noted that Provisional Application No. 62/674,379, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for the limitation “wherein the TLR-mediated inflammatory condition is non-responsive to GABAergic drugs” in claims 1 and 20. Therefore, the instant claims are afforded benefit of priority to PCT/US2019/ 033053, filed May 20, 2019.
39. Finn et al. suggest the treatment of ethanol (EtOH) withdrawal (i.e., alcohol detoxification) and the treatment of alcohol dependence (i.e., alcoholism) comprising administering the GABAergic neurosteroid allopregnanolone (ALLOP):
“While the findings with ALLOP emphasize the therapeutic potential of neurosteroid treatment during EtOH withdrawal, the gene mapping studies suggest that pregnane neurosteroid biosynthesis may represent a target for therapeutic intervention in the treatment of alcohol dependence,”
(see abstract).
40. Finn et al. teach that during EtOH withdrawal, the GABAergic drug diazepam (a benzodiazepine) produced a cross-tolerance effect to EtOH and positive modulators of GABAA receptors (page 98, left column, last 7 lines). A GABAergic drug that promotes EtOH tolerance meets the limitation of the inflammatory condition (alcoholism) not being responsive to a GABAergic drug.
41. Finn et al. additionally teach that ALLOP administration during EtOH withdrawal in female rats enhanced the sensitivity of GABAA receptors. (Page 98, left column, last 7 lines).
42. Finn et al. are silent to alcoholism or alcohol detoxification being a TLR-mediated condition.
43. Yet, Liu et al. teach that GABAA regulated TLR4 expression is upregulated in binge drinking and likely implicated in excessive drinking (i.e., alcoholism):
“GABAA α2-regulated TLR4 expression … contributes to binge drinking and may be a key early neuroadaptation in excessive drinking”
(see abstract).
44. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to treat alcohol detoxification and/or alcoholism (wherein TLR4 is implicated) in a subject in need thereof by administering the GABAergic neurosteroid allopregnanolone to said subject, with a reasonable expectation of success.
Thus, claims 1, 7, 19, 20, 24 and 25 are prima facie obvious.
Claim 3 is drawn to claim 1, and limits wherein the neurosteroid is an inhibitor of toll-like receptor signaling or corticotropin (CRF) releasing hormone signaling, (more specifically, TL4 receptor signaling (claim 4)).
45. Regarding the limitations describing the neurosteroid in claims 3 and 4, while Finn et al. do not teach the ability of allopregnanolone to inhibit toll-like receptor (TLR) signaling, this inherent property flows from the administration step itself. As subjects suffering the inflammatory condition of alcoholism or alcohol detoxification meet the criteria of a subject in need of allopregnanolone (i.e., an inhibitor of TLR), as taught by Liu et al., the claim as a whole is obviated. MPEP § 2112 (II) states "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC S Calif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products. [emphasis added].
See MPEP 2112.01: Composition, Product, and Apparatus Claims [R-07.2015]
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I. PRODUCT AND APPARATUS CLAIMS — WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT
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Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).
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See also In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971) (Claim 1 was directed to a parachute canopy having concentric circumferential panels radially separated from each other by radially extending tie lines. The panels were separated "such that the critical velocity of each successively larger panel will be less than the critical velocity of the previous panel, whereby said parachute will sequentially open and thus gradually decelerate." The court found that the claim was anticipated by Menget. Menget taught a parachute having three circumferential panels separated by tie lines. The court upheld the rejection finding that applicant had failed to show that Menget did not possess the functional characteristics of the claims.); Northam Warren Corp. v. D. F. Newfield Co., 7 F. Supp. 773, 22 USPQ 313 (E.D.N.Y. 1934) (A patent to a pencil for cleaning fingernails was held invalid because a pencil of the same structure for writing was found in the prior art.).
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II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
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"Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.").
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46. As such, by virtue of administering the neurosteroid allopregnanolone to a subject, one is necessarily administering an inhibitor of TLR2, TLR4 or TLR7.
Therefore, claims 3 and 4 are prima facie obvious.
47. Claims 8 and 9 are rejected under 35 U.S.C. 103(a) as being obvious over Finn et al., Pharmacology and Therapeutics (2004), in view of Liu et al, PNAS (2011), as applied to claims 1, 3, 4, 7 and 20-25, above, and further in view of Kandimalla et al., Nucleic Acids Research (2013).
This rejection is made as a result of Applicant’s amendments to the claims.
Claims 1 and 20 are addressed in detail, above.
Claim 8 is drawn to claim 1, further comprising assaying a sample from the subject for TLR signaling in peripheral blood or cerebrospinal fluid, wherein decreased TLR signaling is an indication of administration of a therapeutically effective amount of allopregnanolone.
Claim 9 is drawn to the method of claim 8, further comprising increasing the amount of allopregnanolone administered to the subject if decreased TLR signaling in the peripheral blood mononuclear cells or cerebrospinal fluid is not detected in the sample.
Claim 22 is drawn to claim 20, further comprising assaying a sample from the subject for TLR signaling in peripheral blood or cerebrospinal fluid, wherein decreased TLR signaling is an indication of administration of a therapeutically effective amount of allopregnanolone.
Claim 23 is drawn to the method of claim 22, further comprising increasing the amount of allopregnanolone administered to the subject if decreased TLR signaling in the peripheral blood mononuclear cells or cerebrospinal fluid is not detected in the sample.
**In view of a broadest reasonable interpretation of claims 9 and 23, the limitation of “peripheral blood mononuclear cells” is construed to mean “peripheral blood cells.”
47. Finn et al. in view of Liu et al. suggest the treatment of alcoholism or alcohol detoxification in a subject in need thereof comprising administering allopregnanolone to said subject, wherein the alcohol detoxification is nonresponsive to a GABAergic drug, but do not teach the step of assaying a sample from the subject for TLR signaling in peripheral blood or cerebrospinal fluid, wherein decreased TLR signaling is an indication of administration of a therapeutically effective amount of allopregnanolone.
48. Yet, Kanimalla et al. teach that following treatment with TLR antagonists in murine and primate subjects in vivo, a sample of peripheral blood obtained from said subjects was assayed, indicating that said TLR antagonists successfully inhibited TLR signaling pathways, i.e., TLR-mediated cytokine induction, (see abstract). Kanimalla et al. go on to teach that the extent and duration of TLR inhibition is dose-dependent upon the antagonist administered, i.e., TLR-mediated immune response increases as the dose amount of TLR antagonist is increased:
“The extent of inhibition of TLR7- and TLR9 mediated immune responses by the antagonist was dependent on the dose of antagonist compound administered and the type of cytokine induced by the TLR agonist (Figure 7A and B and Supplementary Figures S7 and S8). At the lowest dose of antagonist compound 1 (1mg/kg), a 30–55% inhibition of various cytokines induced by TLR7 and TLR9 agonists was observed. The extent of inhibition ranged from 55 to 80% at 5-mg/kg and 90 to 100% at 15-mg/kg dose of antagonist compound 1 for various cytokines induced by TLR7 and TLR9 agonists (Figure 7A and B and Supplementary Figures S7 and S8),”
(page 3955, right column, last paragraph- page 3956, left column, first paragraph, and Figure 7).
49. Thus, the step of assaying levels of TLR in a sample of a subject following treatment with a TLR antagonist does not render novel the known method of administering allopregnanolone to treat alcoholism or alcohol detoxification in a subject in need thereof. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention that assaying for the expression level of a protein that plays a key role in a given disease is beneficial towards improved and effective treatments, and the same applies to the features recited in claims 8-9 and 22-23 of the present application. Therefore, a method for treating a subject suffering from alcoholism or alcohol detoxification, comprising administering an effective amount of the TLR inhibitor allopregnanolone, followed by assaying a sample from said subject for decreased TLR signaling in peripheral blood or cerebrospinal fluid, and/or increasing the amount of allopregnanolone administered to the subject if decreased TLR signaling in the peripheral blood or cerebrospinal fluid is not detected in the sample, is not considered inventive. It would have been prima facie obvious to one skilled in the art to assay a sample of peripheral blood taken from a subject having been treated with a TLR antagonist, to measure resulting TLR expression levels in said sample, and if necessary, optimize the dose amount of said TLR antagonist, with a reasonable expectation of success.
Therefore, claims 8, 9, 22 and 23 are prima facie obvious.
Response to Arguments
50. Applicant amended the claims to limit the inflammatory condition to sepsis, gastrointestinal disease, COPD, asthma, atherosclerosis, alcohol detoxification, Alzheimer’s disease, and dementia. Applicant traverses the 35 U.S.C. 102(a)(1) rejection and 35 U.S.C. 103 rejections over Rogawski et al. (and further in view of Iori et al.), arguing that prior art of record, individually or combined, does not teach or suggest the use of a neurosteroid for treating the recited list of TLR-mediated inflammatory conditions, as amended.
51. Applicant’s arguments have been considered but are moot because the new grounds of rejection do not rely on Rogawski et al. (alone or in view of Iori et al.), (applied in the prior rejection(s) of record) for any teaching or matter specifically challenged in their argument.
Conclusion
52. Claims 1, 3, 4, 7-9, 19, 20 and 22-26 (renumbered as claims 21-25) are present in the application. Claims 1, 3, 4, 7-9, and 19-25 are rejected. No claim is presently allowable.
53. 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.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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