Detailed Action
The present office action is in response to amendments filed 05 Mar 2026. The finality of the Office Action mailed 05 Dec 2025 is withdrawn.
The period for reply of 3 months set in said Office Action is restarted to begin with the mailing of this letter.
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
Claims 1-3, 12-14, 16-18, and 22-24 of the pending application have been examined on the merits. Acknowledgement is made of the amendments filed 05 Mar 2026. Acknowledgment is made of the cancellation of claims 4-11, 15, 19-21, and 25.
Priority
The claimed priority date of May 7, 2019 stands.
Response to Arguments
Examiner acknowledges applicant amendments filed 05 Mar 2026.
Applicant arguments regarding the rejection of claims 1, 12-14, and 16 under 35 U.S.C. § 103 over WO 2017/067870 (provided in IDS 11/05/21), hereinafter Garrone, have been fully considered and are persuasive. However, a new rejection for claims 1-3, 12-14, 16-18, and 21-24 has been made over Garrone to clarify the arguments of obviousness and remove out the language of anticipation found in the office action mailed 13 Mar 2025. Briefly, claims 1-3 and 12-14 are directed to a pharmaceutical composition comprising trazodone, gabapentin, and at least one pharmaceutically acceptable excipient wherein the weight ratio of trazodone:gabapentin is greater than 1:100 and lower than 1:40. Garrone teaches a pharmaceutical composition of trazodone equal to or higher than 0.01 mg/kg and equal to or lower than 1 mg/kg and gabapentin equal to or higher than 0.1 mg/kg and equal to or lower than 15 mg/kg (pgs. 6-7). Garrone further teaches a weight ratio of trazodone to gabapentin between 1:40 and 10:1 and that the composition should have an ineffective dosage of either drug if taken alone (pgs. 6 and 8). Garrone also teaches specific dosages of preferably less than 150 mg for gabapentin and preferably less than or equal to 15 mg of trazodone (pgs. 7-8). Although Garrone does not disclose the weight ratio of trazodone to gabapentin strictly greater than 1:100 or lower than 1:40, it indicates that the relative amounts of trazodone and gabapentin may be varied broadly to achieve the desired dosage and it would have been prima facie obvious to the person of ordinary skill in the art to optimize the relative amounts of trazodone and gabapentin, including using trazodone at a low amount relative to gabapentin, through routine experimentation in order to balance efficacy and tolerability. The optimization of such result-effective variables is ordinarily within the level of ordinary skill in the art. The affidavit filed 14 Jul 2025 is not considered persuasive for overcoming this prima facie case for obviousness. See In re Aller, 220 F.2d 454 (CCPA 1955) and MPEP § 2144.05.
Claims 16-18 and 22-24 are directed towards a method of treating pain resulting from post-herpetic neuralgia, post-surgical neuropathic pain, or diabetic neuropathy by administering the pharmaceutical composition of claim 1. Garrone teaches that the pharmaceutical composition above is effective for the treatment of pain and teaches preferred examples of pain treatment to be neuropathic pain induced by diabetes, post-herpetic syndrome, and trauma (pg. 5, lines 10-14 and pg. 12, lines 1-3). The affidavit filed 14 Jul 2025 is not considered persuasive for overcoming this case for obviousness.
Applicant arguments regarding the obviousness-type double patenting rejections over U.S. Patent No. 10,786,498, hereinafter ‘498, and U.S. Patent No. 11,752,147, hereinafter ‘147, have been fully considered and are persuasive. ‘498 is directed to a pharmaceutical composition comprising a synergistic combination of trazodone and gabapentin in a weight ratio between 1:20 and 1:10 of trazodone to gabapentin. Applicant arguments are persuasive that it would be unexpected for the artisan to find synergism between gabapentin and trazodone outside the weight ratios taught by ‘498. ‘147 is directed to methods of treating pain by administering a pharmaceutical composition comprising a synergistic amount of trazodone and gabapentin in a weight ratio of 1:15 to 1:5 of trazodone to gabapentin. Applicant arguments are persuasive because the instant claims are outside the patented ranges and represent a different embodiment of the reference inventions.
Applicant arguments regarding the rejection of claims 1-3, 13, and 16-18 under 35 USC 103 over Dworkin et al. (Mayo Clin Proc, 2010, 85(supplementary):S3-S14), hereinafter Dworkin, in view of Wilson (J Am Podiatr Med Assoc, 1999, 89:468-471), hereinafter Wilson, are not considered persuasive for the reasons below.
On pgs. 16-17 of the remarks filed 14 Jul 2025, applicant argues that a skilled artisan would not have had motivation to specifically use a ratio lower than 1:40, even less the ratio 1:72 resulting from the maximum dosage of gabapentin and trazodone. Applicant argues that the artisan would have been aware that the dosing of gabapentin requires careful titration and that treatment should be initiated at low dosages with gradual increases until pain relief, dose-limiting adverse effects, or 3600 mg/day. Applicant further argues that no artisan would have started the treatment with more than 2000 mg/day of gabapentin and no artisan would have started the treatment with less than 50 mg/day of trazodone.
Examiner respectfully notes that each element of the claim limitation was found in the art at the time of filing. Dworkin teaches that treatment of neuropathic pain with gabapentin at a maximum dosage of 3600 mg/day and that one having ordinary skill in the art would consider combination therapy for patients experiencing partial pain relief. Wilson teaches administering 50 mg/day of trazodone to treat diabetic neuropathy. Creating a composition of gabapentin at 3600 mg/day and trazodone at 50 mg/day would result in a trazodone:gabapentin weight ratio of 1:72 with the expected result of treating neuropathic pain. Further, a dose of 50 mg/day of trazodone per 3600 mg/day of gabapentin is equivalent to when trazodone is 1.39 mg and gabapentin is 100 mg. MPEP § 2143(I)(A) states, "The rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art." See also In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) which states, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Furthermore, even if no skilled artisan would have started treatment at 2000 mg/day, there is no suggestion in the art which would have kept the artisan from arriving at 3600 mg/day for a patient as the maximum recommended dose of gabapentin.
In light of the discussion above, the rejection of claims 1-3, 13, and 16-18 under 35 USC § 103, as obvious over Dworkin in view of Wilson is maintained for the reasons of record and restated below.
A new grounds of rejection under 35 U.S.C. § 102(a)(1) over Supasitthumrong et al. (Br J Clin Pharmacol, 2019, 85:690-703) is made below. Further, a new grounds of rejection for claims 1-3, 12-14, 16-18, and 22-24 under 35 U.S.C. § 112(b) is made below.
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.
Claims 1-3, 12-14, 16-18, and 22-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 1 includes masses of trazodone and gabapentin which would have ratios of 1:40 and 1:100. For example, when trazodone is 2.50 mg and gabapentin is 100 mg, the weight ratio of trazodone to gabapentin would be 1:40. The claim, however, does not allow for weight ratios of trazodone to gabapentin to be equal to 1:40 or 1:100. Claims 2-3, 12-14, 16-18, and 22-24 are rejected for failing to remedy the deficiencies of claim 1. Applicant may overcome this rejection by amending claim 1 to include the ratios of 1:40 and 1:100 or amending the claim to limit the masses to fall within the claimed w/w ratio.
Further regarding claim 1, claim 1 includes the limitation, “wherein said pharmaceutical composition comprises a quantity of first active ingredient equivalent to a quantity of trazodone between 2.50 and 1.00 mg, for a quantity of second active ingredient equivalent to 100 mg of gabapentin.” It is unclear exactly how the relationship between trazodone and gabapentin is to be interpreted within the claim. The term “equivalent” may have two meanings; it may mean equivalent to the exact amount of each component or equivalent to the ratio of components. The specification does not provide a clear definition to help clarify the interpretation of the term “equivalent” in the claims. MPEP § 2173.05(b)(II) states, “A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989).” Therefore, because the relationship between the limitation and the object of the claim is not sufficiently defined, the claim is indefinite. Claims 2-3, 12-14, 16-18, and 22-24 are rejected for failing to remedy the deficiencies of claim 1. Applicant may overcome this rejection by amending the claim to clarify the definition of the term “equivalent” in claim 1.
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.
Claim 13 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 13 limits the pharmaceutical composition of claim 1 to a single dosage form of trazodone and gabapentin or a first dosage form of trazodone and a second dosage form of gabapentin. However, these are the only two options which an artisan would understand the pharmaceutical composition of claim 1 to mean. 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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Supasitthumrong et al. (Br J Clin Pharmacol, 2019, 85:690-703), hereinafter Supasitthumrong.
Supasitthumrong teaches the treatment of a patient with 3600 mg/day of gabapentin and up to 150 mg/day trazodone in 25 mg doses, with effects being seen at 75-100 mg of trazodone (pg. 693, column 2). When dosed with 75 mg of trazodone, the patient was treated with a weight ratio of trazodone to gabapentin of 1:72. Further, 75 mg of trazodone is equivalent to 2.08 mg of trazodone when gabapentin is 100 mg. Supasitthumrong thus anticipates instant claims 1-4.
Claim Rejections - 35 USC § 103
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3 and 12-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garrone.
Garrone teaches a pharmaceutical composition of trazodone equal to or higher than 0.01 mg/kg and equal to or lower than 1 mg/kg and gabapentin equal to or higher than 0.1 mg/kg and equal to or lower than 15 mg/kg (pgs. 6-7). Garrone further teaches a weight ratio of trazodone to gabapentin between 1:40 and 10:1 and that the composition should have an ineffective dosage of either drug if taken alone (pgs. 6 and 8). Garrone also teaches specific dosages of preferably less than 150 mg for gabapentin and preferably less than or equal to 15 mg of trazodone (pgs. 7-8). Garrone teaches that physiologically acceptable organic and inorganic salts of trazodone and gabapentin are included in the scope of the composition and that the formulations may be tablets, capsules, coated tablets, and solutions for oral administration (pgs. 9-10). Garrone teaches the pharmaceutical composition of the reference may be administered to treat neuropathic pain induced by diabetes, post-herpetic syndrome, and trauma (pg. 5, lines 10-14 and pg. 12, lines 1-3). However, Garrone does not disclose the weight ratio of trazodone to gabapentin strictly greater than 1:100 or lower than 1:40.
Based on the teachings of Garrone, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the instantly claimed pharmaceutical composition by varying the amounts of the trazodone and gabapentin in order to treat neuropathic pain induced by diabetes, post-herpetic syndrome, and trauma. Garrone indicates that the relative amounts of trazodone and gabapentin may be varied broadly to achieve the desired dosage and the artisan would optimize the relative amounts of trazodone and gabapentin, including using trazodone at a low amount relative to gabapentin, through routine experimentation in order to balance efficacy and tolerability. The optimization of such result-effective variables is ordinarily within the level of the artisan. See MPEP § 2144.05.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 1-3, 13, 16-18, and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dworkin and Wilson as in the Office Action filed October 1, 2024 and restated below.
Dworkin teaches treatment of neuropathic pain with gabapentin at a maximum dosage of 3600 mg/day (Table 2). Dworkin also teaches combination therapy for patients experiencing partial pain relief (Table 1, step 3). However, Dworkin does not teach the use of trazodone to treat neuropathic pain.
Wilson teaches 50 mg of trazodone is able to treat painful diabetic neuropathy in some patients with success (Table 1).
By combining the treatment of painful diabetic neuropathy with trazodone starting at 50 mg/day in a first dosage form with treating neuropathic pain with gabapentin at a dosage of 3600 mg/day in a second dosage form, it would be obvious to one of ordinary skill in the art to use a trazodone to gabapentin weight ratio of 1:72 to treat painful diabetic neuropathy.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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