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 .
Withdrawn Rejections
The rejection of claims 1-3, 8-9, 13-14, 16, 18-25, 33-34, 36-41, 44-45, 48-49 and 55 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn because of the amendment of the claims to correct the indefiniteness.
The rejection of claims 1-3, 8-9, 18-25, 33-34, 37-41, 44-45, 48-49 and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smyth of record (U.S. Pub. No. 20130338172), is withdrawn because of the cancellation of claim 1.
Status of the Claims
Claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 36-38, 40-41, 44-45, 48-49 and 55-76 are pending.
Applicants’ arguments, filed on 10/06/2025, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments filed on 10/06/2025, have been fully considered. Applicants have amended claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 36-38, 40-41 and 55. Applicants have cancelled claims 1-2, 19 and 39. Applicants have newly added claims 56-76. Therefore, claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 36-38, 40-41, 44-45, 48-49 and 55-76 are subject of the Office action below.
Claim Objections
Claims 18 and 55 are objected to under 37 CFR 1.71(a) because the claims are presented using an incorrect status identifier. Claims 18 and 55 are presented as “Withdrawn & Currently Amended”, however, the Restriction Requirements mailed on 07/30/2024, has been withdrawn (see Office action mailed on 04/04/2025). Please see MPEP § 714. Appropriate correction is required.
Claim Rejections - 35 USC § 112
New Grounds of Rejection Necessitated by Applicant’s Amendments
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 14 and 16 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.
Each of claims 14 and 16 recites the limitation “the pharmaceutical composition of crospovidone”. There is insufficient antecedent basis for this limitation in the claims. Claims 14 and 16 lack antecedent basis because claim 20 from which claims 14 and 16 depend fails to recite “a pharmaceutical composition of crospovidone”. Appropriate correction is required.
Claim Rejections - 35 USC § 112-4th Paragraph
New Grounds of Rejection Necessitated by Applicant’s Amendments
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 57 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 57 recites that the filler is microcrystalline cellulose, which does not appear further limit claim 20, the claim upon which claim 57 depends. Claim 20 recites that the filler is microcrystalline cellulose.
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 § 103
Maintained/New Grounds of Rejection Necessitated by Applicant’s Amendments
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.
The rejection of claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 37-38, 40-41, 44-45, 48-49 and 55, is maintained and newly added claims 56-76 are rejected under 35 U.S.C. 103 as being unpatentable over Smyth of record (U.S. Pub. No. 20130338172), for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
Independent claim 20 is drawn to a solid tablet formulation comprising:
a) about 50wt% to about 80 wt% ibrutinib (compound 1):
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b) 10-30 wt% of microcrystalline cellulose (a filler);
c) 5-20 wt% of a disintegrant;
d) one or more additional pharmaceutically acceptable excipients.
Regarding claim 20, Smyth (see table 6), teaches a tablet formulation comprising:
5-50 wt% compound 1;
5-50 wt% microcrystalline cellulose (a filler, see ¶ 0444);
0 wt% to 15 wt% croscarmellose sodium (a disintegrant, see ¶ 0087);
2-10 wt% hypromellose (binder, see ¶ 0453, i.e., additional excipient);
0.25-2.5 wt% magnesium stearate (lubricant, see ¶ 0087, i.e., additional excipient); and
10-75 wt% lactose (diluent, see ¶ 0087, i.e., additional excipient).
Ibrutinib, microcrystalline cellulose and magnesium stearate are intragranular ingredients (see Table 2, page 71 of the specification).
Magnesium stearate is an extragranular ingredient (see Table 2, page 71 of the specification).
Manufacturing process will typically be granulation (dry, wet or melt) or direct compression (see ¶ 0634).
The claimed wt% of tablet formulation components recited in claim 20, overlap or lie inside ranges disclosed by Smyth (see discussions above).
A prima facie case of obviousness exists in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" (see MPEP § 2144.05).
In the instant case, because the claimed wt% of tablet formulation components, overlap or lie inside ranges disclosed by Smyth (see discussions above), a prima facie case of obviousness exists. Therefore, claim 20 is obvious over Smyth.
Regarding claim 3, Smyth did not teach mannitol (see Table 6).
Regarding claim 9, 61 Smyth teaches intragranular ingredients (see discussions above).
Regarding claims 13-14, 16 and 56, Smyth teaches disintegrant selected from the group consisting a list that includes crospovidone (see ¶ 0087) and in an amount ranging from about 3% w/w to about 10% w/w (see ¶ 0084).
Regarding claims 16, 20-21, 58-59, 62-64, 67 and 70, the claimed component wt% ranges are result effective variables that would have been routinely determined and optimized in the pharmaceutical art. For example, Smyth discloses that compound 1 can administered in an amount ranging from about 0.5 mg to about 1000 mg (see ¶s 0087, 0486-0487). Amount of compound 1 would depend on use (e.g., therapeutic, prophylactic, or maintenance), severity and course of the disease or condition, previous therapy, the patient's health status, weight, and response to the drugs, and the judgment of the treating physician (see ¶ 0489).
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
It is noted that no criticality (emphasis added) has been demonstrated in the specification with regard to the claimed component wt% ranges.
Regarding claims 18 and 55, Smyth discloses dry granulation (see discussions above).
Regarding claims 22-25, Smyth discloses that in an embodiment, the composition can comprise from about 2-7 wt% sodium lauryl sulfate (see ¶ 0092).
The claimed wt% of sodium lauryl sulfate recited in claim 25, overlap or lie inside ranges disclosed by Smyth (see discussions above).
A prima facie case of obviousness exists in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" (see MPEP § 2144.05).
In the instant case, because the claimed wt% of sodium lauryl sulfate, overlap or lie inside ranges disclosed by Smyth (see discussions above), a prima facie case of obviousness exists. Therefore, claims 22-25 are obvious over Smyth.
Regarding claim 33, Smyth (see ¶ 0449), discloses that the pharmaceutical solid dosage form of the invention can comprise compound 1 and one or more pharmaceutically acceptable additives such as a compatible carrier, binder, filling agent, Suspending agent, flavoring agent, sweetening agent, disintegrating agent, dispersing agent, surfactant, lubricant, colorant, diluent, Solubilizer, moistening agent, plasticizer, stabilizer, penetration enhancer, wetting agent, anti-foaming agent, antioxidant, preservative, or one or more combination thereof.
Accordingly, at the time of the instant invention, a person skilled in the art would have understood that Smyth contemplates a pharmaceutical solid dosage form that does not contain a binder. Therefore, one skilled in the art would have envisaged a pharmaceutical solid dosage form that does not contain a binder, in the Smyth disclosure.
Regarding claims 34 and 71, Smyth (see, e.g., ¶ 0486), teaches compound 1 in an amount from 300 mg and up to 1000, including 560 mg, 840 mg.
Regarding claim 37, Smyth teaches once a day dosing (see ¶ 0486).
Regarding claim 38, Smyth teaches tablet (see discussions above).
Regarding claims 40-41, 44-45 and 48-49, Smyth teaches that an embodiment of the invention provides for a method of treating autoimmune diseases or conditions, hyperimmune diseases or conditions, cancer, and inflammatory diseases or conditions, selected from the group that includes the list recited in the instant claims, with a composition comprising compound 1. Please see abstract, ¶s 0191-0192 and Examples 12-14.
Regarding claims 57 and 60, Smyth teaches microcrystalline cellulose (see discussions above), which necessarily encompasses silicified microcrystalline cellulose.
Regarding claims 65-66, Smyth (see ¶ 0450), discloses colloidal silicon dioxide (a silica, see page 5 of the specification), among suitable carriers for use in the solid dosage forms of the invention.
Regarding claims 68-69, Smyth (see discussions above), teaches magnesium stearate.
Regarding claims 72-73, Smyth (see ¶ 0447), discloses that dosages forms such as tablets may also include film coatings.
Regarding claims 74-75, the recited bioavailability of a solid tablet of claim 20, is the bioavailability of the tablet, when the tablet is administered to a patient in need thereof. Since Smyth discloses a tablet of claim 20 (see discussions above), the tablet of Smyth must necessarily exhibit the same bioavailability recited in claims 74-75.
An inherent characteristic may “be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan.” Endo Pharm. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374, 1381 (Fed. Cir. 2018).
Regarding claim 76, Smyth (see ¶ 0448), teaches dry granulation, which necessarily encompasses roller granulation.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). 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. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference.
Response to Applicants’ Arguments
Applicants raised several arguments (see pages 10-13 of Remarks), alleging that the claimed invention is non-obvious over the cited prior art on the grounds that:
1) Applicants’ claimed invention is directed to solid tablet formulation comprising dry granules that have intragranular and extragranular components (see pages 10-11 of Remarks).
Response:
Applicant’s arguments have fully been considered but they are not found to be persuasive, because Smyth discloses a tablet formulation within the tablet components limitations of the claimed invention (e.g., claim 20, see discussions above).
2) Smyth fails to teach the claimed bioavailability and pharmacokinetic properties of tablets of the claimed invention (see pages 10-13 of Remarks).
Response:
Applicant’s arguments have fully been considered but they are not found to be persuasive. This is because each of the claimed bioavailability and pharmacokinetic properties of a solid tablet of instant claims, is the bioavailability and pharmacokinetic properties of the tablet, when the tablet is administered to a patient in need thereof. Since Smyth discloses a tablet of the claimed invention and a method for administering the tablet to a patient in need thereof (see discussions above), the tablet of Smyth must necessarily exhibit the same bioavailability and pharmacokinetic properties Applicants are claiming. This is because each of the bioavailability and pharmacokinetic properties is a natural process that flows from the patient and the tablet administered.
An inherent characteristic may “be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan.” Endo Pharm. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374, 1381 (Fed. Cir. 2018).
3) A person skilled in the art would not have envisaged a tablet of the claimed invention from the disclosure of Smyth because various ¶s of Smyth allegedly disclose thousands of components (see page 11 of Remarks).
Response:
Applicant’s arguments have fully been considered but they are not found to be persuasive.
This is because, similar to the Applicants’ invention, Smyth discloses ibrutinib as the only active ingredient in the claimed tablet formulation comprising the same excipients Applicants are claiming. Smyth discloses a tablet formulation and components amounts where the claimed ranges "overlap or lie inside ranges disclosed by Smyth. Please see discussions above.
A prima facie case of obviousness exists in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" (see MPEP § 2144.05). Therefore, at the time of the instant invention, one skilled in the art would have envisaged a tablet of the claimed invention, in the Smyth disclosure.
4) Smyth fails to teach or suggest preparation of high-load tablet formulation comprising high levels of ibrutinib (see pages 11-12 of Remarks).
Response:
Applicant’s arguments have fully been considered but they are not found to be persuasive.
This is because, similar to the Applicants’ invention, Smyth discloses ibrutinib tablet formulation in an amount within the claimed ibrutinib amounts (see discussions above).
Furthermore, the limitation of a “high-load” tablet formulation comprising “high levels” of ibrutinib is not recited in the instant claims.
The rejection of claims 20 and 36 under 35 U.S.C. 103 as being unpatentable over Smyth of record (U.S. Pub. No. 20130338172), as applied to claim 20 above and in view of Gujjar of record (EP2902016A1), is maintained for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
The limitations of claim 20, as well as the corresponding teachings of Smyth, are discussed above, and are hereby incorporated into the instant rejections.
Claim 36 is similar to claim 20, however, claim 36 differs slightly from claim 20 in that claim requires ibrutinib in a micronized form.
Although Smyth is not explicit in teaching micronized ibrutinib, the claimed invention would have been obvious over Smyth, because at the time of the instant invention, it was known in the art that the dissolution rate of a drug can be enhanced by micronizing the drug.
For example, Gujjar discloses a method of increasing the dissolution of a drug by micronizing the drug and subjecting a composition comprising the drug to dry granulation or wet granulation (similar to Smyth, see discussions above). Please see ¶s 0011, 0013 and 0024-0025.
Therefore, at the time of the instant invention, one skilled in the art would have found it obvious to employed a micronized form of compound 1 of Smyth, with a reasonable expectation that the dissolution rate of the micronized compound would be increased. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Response to Applicants’ Arguments
Applicants argue (see page 13 of Remarks), alleging Gujjar cannot be employed to address the deficiency in the teachings of Smyth because Gujjar relates to a completely different active agent (see page 13 of Remarks).
Response:
Applicant’s arguments have fully considered but they are not found to be persuasive. This is because Gujjar was cited for teaching that the dissolution rate of a drug can be enhanced by micronizing the drug (see discussions above). At the time of the instant invention, one skilled in the art would have found it obvious to employed a micronized form of compound 1 of Smyth, with a reasonable expectation that the dissolution rate of the micronized compound would be increased. Please see discussions above.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Therefore, use of Gujjar in order to address the deficiency in the teachings of Smyth, is proper.
Non-Statutory Obviousness-Type Double Patenting-Maintained
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 rejection of claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 37-38, 40-41, 44-45, 48-49 and 55, is maintained and newly added claims 56-76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 9,158,847, in view of: i) Smyth of record (U.S. Pub. No. 20130338172, published); and ii) Gujjar of record (EP2902016A1), is maintained for the reasons of record set forth in the Office action.
The provisional rejection of claims 3, 9, 13-14, 16, 18, 20-25, 33-34, 37-38, 40-41, 44-45, 48-49 and 55, is maintained and newly added claims 56-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Application Nos: 1) 17/992,348; and 18/304,685, in view of: i) Smyth of record (U.S. Pub. No. 20130338172, published); and ii) Gujjar of record (EP2902016A1), is maintained for the reasons of record set forth in the Office action.
Response to Applicants’ Arguments/Remarks
Applicants have not properly addressed the specific grounds of rejections as discussed in the previous Office action setting. Applicants request that the obvious-type double patenting rejections be held in abeyance. Please see page 14 of Remarks.
Response
Applicants’ comments are acknowledged. However, the rejections will be maintained until a terminal disclaimer is filed or the claims are amended to obviate the rejections.
Conclusion
No claim is allowable.
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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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629