DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election with traverse Group I (drawn to a method of treating an inflammatory condition in a human subject), in the reply filed on 03/13/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-19 are pending of which, claims 9-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected INVENTION, there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 1-8 have been examined on the merits.
Response to argument
Applicant's election with traverse of Group I in the reply filed on 03/13/2025 is acknowledged. The traversal is on the ground(s) that the Group I - V are not independent, but rather are natural outcomes of the treatment for the inflammatory condition described in Group I. This is not found persuasive because each group represents a distinct medical use: treating inflammation, reducing homocysteine, or lowering cardiovascular risk, as an example. These are recognized as separate therapeutic indications, and the effects cannot be assumed to occur together for all treatments. Therefore, the subject matter for each group must be considered independently. The requirement is still deemed proper and is therefore made FINAL.
Maintained Rejection
Claim Rejections - 35 USC § 103(a)
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 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 1-6 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Crea (USPN 7,713,569) in view of Nelson (WO 2005/041999).
Applicant claims a method for treating an inflammatory condition in a human subject comprising administering a hydroxytyrosol-rich composition (i.e. as disclosed within Applicant's specification on pages 7-8, the claimed hydroxytyrosol-rich composition is prepared from olive vegetation water) to the subject, monitoring improvement in the subject according to a reduction in the subject's homocysteine levels, and continuing said administering an amount and for a period sufficient to effect a decrease in the homocysteine levels of at least of a claimed percentage and/or within a normal range of homocysteine.
Crea teaches a method for treating several disorders including claimed inflammatory conditions in a human subject comprising administering the same claimed hydroxytyrosol-rich composition (i.e. Crea's hydroxytyrosol-rich composition is also prepared from olive vegetation water) as the claimed invention's hydroxytyrosol-rich composition to a subject. Please note that the instantly claimed in vivo functional effect (i.e. the functional effect of decreasing homocysteine levels of at least of a claimed percentage and/or within a normal range of homocysteine to treat inflammation conditions) of Crea administering the same claimed hydroxytyrosol-rich composition as the claimed invention's hydroxytyrosol-rich composition would be intrinsic upon such administration to a subject (see, entire patent including e.g. column 14 lines 40-48 and column 15 lines 11-12 and lines 35-41). Crea, however, does not teach the claimed step of monitoring improvement in the subject according to a reduction in the subject's homocysteine levels.
Nelson teaches when treating an inflammation condition, homocysteine levels are reduced (see, entire document including e.g. abstract and page 9, line 23-27).
It would have been obvious to one of ordinary skilled in the art at the time the invention was made to modify Crea's method steps of treating inflammation conditions to include another step of monitoring improvement in the subject according to a reduction in the subject's homocysteine levels since Nelson beneficially teaches when treating an inflammation condition, homocysteine levels are reduced because the combined two teachings as a whole would create the claimed invention of a method of administering Crea's same hydroxytyrosol-rich composition to a subject, monitoring improvement in the subject according to a reduction in the subject's homocysteine levels as beneficially suggested and/or taught by Nelson, in order to intrinsically provide the in vivo functional effect of decreasing homocysteine levels upon administration in a
subject to treat inflammation conditions in a subject. Furthermore, the adjustment of conventional working conditions therein (e.g., determining suitable amount of ranges of each claimed active ingredient within the composition and/or the modification of the dose per day), is deemed merely a matter of judicious selection and routine optimization, which is well within the purview of the skilled artisan. Accordingly, the claimed invention would have been found to be prima facie obvious to one of ordinary skill in the art at the time the invention was made, especially in the absence of evidence to the contrary.
Claims 7-8 are rejected under 35 U.S.C. 103(a) as being unpatentable
over Crea (A*, US PG-PUB 2003/0108651) and Nelson (WO 2005/041999), as applied to claims 1-6 above, and further view of Lazzerini et al. (U*, Reduction in plasma homocysteine level in patients with rheumatoid arthritis given pulsed glucocorticoid treatment, see website article of http://ard.bmj.com/content/62/7/694.full, page 694-695, accepted December 2002).
Regarding claims 7-8, the combined teachings of Crea and Nelson teach a method for treating inflammatory conditions in a human subject comprising administering a hydroxytyrosol-rich composition to a subject. Crea and Nelson do not explicitly teach inflammatory condition of
rheumatoid arthritis.
Lazzerini, however, does not teach the claimed step of monitoring improvement in
the subject in need thereof having the instantly claimed inflammatory condition of
rheumatoid arthritis.
The cited reference of Lazzerini beneficially teaches when one treats an
inflammatory condition of rheumatoid arthritis, lower levels of inflammation in a subject
in need thereof with rheumatoid arthritis contributes to the reduction of plasma
homocysteine levels in a subject in need thereof. (Please note also that Lazzerini
discloses on page 1 that a patient with rheumatoid arthritis given steroid pulse therapy
showed an early and progressive reduction in homocysteine plasma levels). (see, entire
document including e.g. pages 1-2).
It would have been obvious to one of ordinary skilled in the art at the time the
invention was made to modify Crea's method steps of treating inflammation conditions
in a subject to include the step of monitoring improvement in the subject in need thereof
having the instantly claimed rheumatoid arthritis according to a reduction in the subject's
plasma homocysteine levels since Lazzerini beneficially teaches when one treats an
inflammatory condition of rheumatoid arthritis, lower levels of inflammation in a subject
in need thereof with rheumatoid arthritis contributes to the reduction of plasma
homocysteine levels in a subject in need thereof. One of ordinary skill in the art would
have been motivated with a reasonable expectation of success to include the step of
monitoring improvement in the subject in need thereof having the instantly claimed
rheumatoid arthritis according to a reduction in the subject's plasma homocysteine
levels since the step of monitoring improvement in the subject in need thereof having
the instantly claimed rheumatoid arthritis would aid in obtaining the claimed inventions
method for treating an inflammatory condition such as rheumatoid arthritis in a subject
in need thereof.
Therefore, the combined cited references of Crea, Nelson and Lazzerini as a
whole to create the claimed invention of a method of administering a hydroxytyrosol-rich
composition to a subject to treat an inflammatory condition such as rheumatoid arthritis,
monitoring improvement in the subject having the instantly claimed inflammatory
condition of rheumatoid arthritis according to a reduction in the subject's plasma
homocysteine levels, in order to intrinsically provide the in vivo functional effect of
decreasing homocysteine levels upon administration in a subject to treat an
inflammation condition such as rheumatoid arthritis in a subject in need thereof.
Furthermore, the adjustment of other conventional working conditions therein (e.g.,
determining suitable amount/ranges of each claimed active ingredient within the
composition and/or the modification of the dose per day and a sufficient time period to
be an effective treatment), is deemed merely a matter of judicious selection and routine
optimization which is well within the purview of the skilled artisan.
Accordingly, the claimed invention was prima facie obvious to one of ordinary
skill in the art at the time the invention was made, especially in the absence of evidence
to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine
grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or
improper timewise extension of the “right to exclude” granted by a patent and to prevent possible
harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where
the conflicting claims are not identical, but at least one examined application claim is not
patentably distinct from the reference claim(s) because the examined application claim is either
anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may
be used to overcome an actual or provisional rejection based on nonstatutory double patenting
provided the reference application or patent either is shown to be commonly owned with the
examined application, or claims an invention made as a result of activities undertaken within the
scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination
under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §
2146 et seq. for applications not subject to examination under the first inventor to file provisions
of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be
accompanied by a reply requesting reconsideration of the prior Office action. Even where the
NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used.
Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or
PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely
online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 16 of U.S. Patent No. US 8216599 in view of Crea
(US 7,713,569) and Nelson (WO 2005/0113287).
Although the claims at issue are not identical, they are not patentably distinct from each
other because compounds claimed in US patent '599 are comparable to those of the instant
claims. For example, the instant claims recite a method of treating an inflammatory condition in a human subject by administering a hydroxytyrosol-rich, comprising hydroxytyrosol and oleuropein ratios between about 10:1 and about 100:1, while monitoring homocysteine biomarker. US patent '599 teaches a similar composition with the main exception of monitoring C-reactive protein instead. Since both the instant claims and US patent '599 are directed to treating “subject having inflammatory disease,” thus, the patient population substantially overlap and are not meaningful distinct, despite monitoring different biomarkers. The fact that a different biomarker is measured does not confer patentable distinction, because both claims are directed to the same core therapeutic method of treating inflammatory disease with hydroxytyrosol-rich composition or hydroxytyrosol and oleuropein ratios. Thus, the difference in biomarker analysis alone does not render the invention patentably distinct. Thus, the instant claim is not patentably distinct from the claims of US patent '599, and allowance would improperly extend patent protection for the same invention or an obvious variant therefor.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 10-11 of U.S. Patent No. USPN 9,789,149 in view of Crea
(USPN 7,713,569) and Nelson (WO 2005/041999).
Although the claims at issue are not identical, they are not patentably distinct from each
other because compounds claimed in US patent '149 are comparable to those of the instant
claims. For example, both the instant claims and US patent '149 are directed to composition hydroxytyrosol-rich composition, comprising hydroxytyrosol and oleuropein ratios between about 10:1 and about 100:1 for treating inflammatory disease. US patent '149 discloses hydroxytyrosol-rich composition having hydroxytyrosol and oleuropein ratios within the recited range, and explicitly teaches use for treating inflammatory skin disease, which are subset of inflammatory diseases. Although the instant claim further specifies treatment of subjects with “elevated homocysteine,” that subgroup is encompassed with the population of patients treated in US patent '149. Thus, the instant claim is not patentably distinct from the claims of US patent '149, and allowance would improperly extend patent protection for the same invention or an obvious variant therefor.
Response to Arguments
Applicant argues that Nelson does not teach “monitoring” homocysteine levels as step of a method of treatment. Applicant also argues that neither Nelson or Crea does not teach or suggests “continuing said administering in an amount and for a period sufficient to effect
a drop in homocysteine level of at least 7. 5%.” Applicant’s argument is not persuasive because the combined teaching of Nelson and Crea explicitly teach reduction of homocysteine levels as a desirable feature in treating inflammatory joint conditions, as such reductions in homocysteine levels indicate improvement. Thus, a POSITA would inherently monitor homocysteine, while considering to adjust dose and treatment duration accordingly. In addition, selecting a specific threshold, e.g., 7.5%, reduction is merely a routine optimization; because the combined teaching of Nelson and Crea links therapy, homocysteine reduction, and clinical benefit as and effective treatment approach. Therefore, a POSITA would have reasonably expected that optimizing frequency and target homocysteine levels is a matter of routine clinical practice, with homocysteine levels adjusted or evaluated to reflect treatment effectiveness. Furthermore, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that the prior art does not teach or suggests the claimed oral dosage ranges of about 5.4 mg to 10.8 mg of polyphenols or 2.5 to 5 mg of hydroxytyrosol. Applicant argument is not persuasive because Crea (page 5-6, [0087]) discloses hydroxytyrosol-rich injectable formulations at 1-500 mg/ml, with preferred ranges of 1-100 mg/ml, as an example, with hydroxytyrosol as the primary active ingredient. Therefore, a POSITA would understand that administering 0.5 ml (of 1-100 mg/ml), as an example, would yield a dose of 0.5-50 mg hydroxytyrosol, which clearly encompasses the claimed 2.5-5 mg of hydroxytyrosol. In addition, given that polyphenols are part of that composition and are administered in an “effective amount,” it is reasonable for a POSITA to comprehend that effective polyphenols dosing would include within the same range 0.5-50 mg range at 0.5 ml, which encompasses the claimed 5.4-10.8 mg of polyphenols (Crea, page 10). It is also important to note that hydroxytyrosol-rich composition can also be formulated for oral and topical administration (Crea, page 9, [0120]). Therefore, the instant claim is a clear adaptation of the prior art and represents noting more than routine optimization of dose and formulation as disclose in the prior art.
Furthermore, Applicant’s assertion that “optimization” in the office action is contrary to MPEP, is not persuasive. It is important to remind Applicant, where the prior art teaches the same composition, route(s) of administration, and a broad but overlapping effective dose range, selection of a particular sub-range, and in the claimed invention, is indicative of routine optimization by a POSITA, not as a patentably distinct invention. The fact the prior art and instant claims do use the term “optimize” is irrelevant to the subject matter; the question is whether the claimed doses are merely values encompassed from within the range taught by the prior art.
Applicant also argues that the prior art does not teach “relative to pre-treatment level,” because the phrase “relative to pre-treatment level” is find in the prior art. Applicant’s argument is not persuasive because the combined prior art teaches administering hydroxytyrosol-rich composition in an amount sufficient to produce therapeutic improve such as a reduction in homocysteine levels in patients with rheumatoid arthritis. Therefore, a POSITA would recognize that a therapeutic improvement is measured against the patient’s baseline (pre-treatment) status. For this reason, stating that the treatment continued until biomarker (homocysteine) decreases by a given percentage “relative to pre-treatment” merely quantifies that baseline to post-treatment improvement and reflects routine clinical practice, as disclosed in the prior art that such treatment therapy would lead to a reduction of homocysteine levels.
Applicant further argues that the same “deficiencies” identified with the 103 rejection, also apply to the non-statutory double patent (DP) rejection, thus the DP rejection is not valid. Applicant’s argument is not persuasive because DP rejection is a claim-to-claim comparison between the instant claims and the claims of the reference patent, asking whether the latter claims are patentably distinct, rather comparing to the whole patent reference.
Conclusion
Therefore, claims 1-8 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622