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 .
Applicant’s arguments, filed 17 September 2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 presently being applied to the instant application.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 22-26 and 29-46 are rejected under 35 U.S.C. 103 as being unpatentable over US 2004/0219146 A1 (Schenk, 11/04/2004).
Schenk discloses administration of alum as an enhancer for administration of polypeptide compositions to prevent or treat Alzheimer's disease (AD), a progressive disease resulting in senile dementia, AD being characterized by amyloid deposits such as Aβ (i.e. β-amyloid) in a patient. An effective dosage may comprise an antibody that specifically binds to the amyloid deposit or a component thereof to the patient; or a polypeptide comprising an active fragment of Aβ that induces an immune response to Aβ in the patient. ([0002], [0006], [0012], [0013]). To prepare the dosage with alum, Aβ peptide in PBS (phosphate-buffered saline, i.e. excipient) is added to Alhydrogel® (2% aqueous aluminum hydroxide gel, i.e. alum) to reach desired concentrations of Aβ peptide in 2mg alum in a final dose volume of 200 µl (i.e. 0.2 ml) as a suspension ([0298]), or as AN1792 (i.e. 42 amino acid long Aβ, or Aβ42 as noted by [0192] of Schenk) in PBS added to Alhydrogel® to reach desired concentrations of AN1792 in 5mg alum in a final dose volume of 250 µl (i.e. 0.25 ml) ([0280]). The adjuvants may be administered separately, before, concurrently with, or after administration of the therapeutic agent ([0137]). Schenk further discloses a number of diagnostic tests are available for identifying individuals with Alzheimer’s disease (AD). These include measurement of the CSF (cerebrospinal fluid) tau and Aβ42 levels, as well as diagnosis by Alzheimer’s disease and Related Disorders Association (ADRDA) criteria, which is used to define early- to mid-Alzheimer’s disease using a Mini-Mental State Exam (MMSE) (¶¶ [0128], [0335]).
Together these would provide a method for treating dementia associated with beta-amyloid deposition as instantly claimed. The prior art is not anticipatory insofar as alum is selected from a list of alternative adjuvant choices in the reference. It would have been obvious, however, to make the combination since 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 MPEP 2143(I)(A).
With regards to instantly claimed “aluminum oxyhydroxide”, as noted by page 14 of the instant Specification, Alhydrogel® 2%, Al2O3, or alum, is an aluminum oxyhydroxide wet gel suspension. Thus, the alum, or aluminum hydroxide gel, disclosed by Schenk, meets the limitation of the aluminum oxyhydroxide as claimed.
Regarding the claimed amounts of aluminum oxyhydroxide of claims 22, 30 and 31, the claimed ranges would’ve been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claim 22 reciting aluminum oxyhydroxide as an effective ingredient, as discussed above, Schenk discloses administration of alum as an enhancer in the treatment of Alzheimer's disease, which is characterized by amyloid deposits, such as Aβ (i.e. β-amyloid peptide) in a patient. As such, it would have been obvious to one of ordinary skill in the art that the alum of Schenk delivers an effect (i.e. enhancer) and reasonably appears to meet the limitation of an effective ingredient as instantly claimed.
Regarding claims 29, 38-39, and 41, Schenk further discloses wherein administration of the dosages may be done subcutaneously, in multiple dosages over a period of at least six months ([0009]). Intervals between dosages may be monthly (i.e. claimed at least once monthly). Dosage and frequency of administration can vary depending on whether treatment is prophylactic or therapeutic. Some patients continue to receive treatment for the rest of their lives ([0133]).
Regarding claim 39, although Schenk does not explicitly disclose a location of administration, it would appear to have taken no more than the relative skills of one of ordinary skill in the art to have determined a suitable administration location based on known and effective injection sites.
Regarding claim 41, since Schenk discloses administering subcutaneously, administration by an injection device would flow from such teaching.
Regarding claims 33-36, Schenk does not explicitly disclose the claimed characteristics of Alhydrogel®, such as particle size distribution, anion content, or heavy metal content. However, as noted by pp. 12-14 of the instant Specification, “the Alhydrogel® (i.e. aluminum oxyhydroxide) preparation is devoid of anions, such as sulphates, nitrates, or chlorides and has a specified heavy metal content of less than 20 ppm. The suspension of aluminum oxyhydroxide has a particle size distribution between 2 µm and approximately 10 µm.” Accordingly, since the formulation of Schenk comprises substantially the same components (i.e. Alhydrogel® as the claimed aluminum oxyhydroxide suspension) in about the same amounts, one of ordinary skill in the art would reasonably conclude the formulation of Schenk to reasonably possess the same properties as the claimed invention, such as a particle size distribution between about 2 µm and about 10 µm, be substantially devoid of sulfate, nitrate, or chloride anions, or have a heavy metal content of less than about 20 ppm.
Regarding claim 37, as discussed above, Schenk discloses wherein the formula comprises peptide in PBS added to Alhydrogel®. As noted by Phosphate-buffered saline (Wikipedia, IDS Reference, retrieved May 29, 2017), PBS is isotonic. Therefore, one of ordinary skill in the art would reasonably conclude the formulation of Schenk to be isotonic.
Regarding claim 40, as discussed above, Schenk discloses administering dosages for at least six months, and some patients continue to receive treatment for the rest of their lives. Accordingly, the claimed duration (i.e. at least two years) would have been obvious to one of ordinary skill in the art since it overlaps with the range of the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claim 42 reciting a dose volume, the claimed ranges (i.e. from about 0.1 to about 10ml) would have been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art (i.e. 0.2 or 0.25 ml). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claim 43, the transitional phrase “consists essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s) of the claimed invention” (See MPEP 2111.03(III)). Applicant has not made clear in the instant specification or instant claims any component such as compounds, adjuvants, or additives wherein the addition of such component would constitute a material change in the basic and novel characteristics of the claimed invention or cause a deleterious effect to the claimed invention. Therefore, for the purposes of searching for and applying prior art under 35 U.S.C. 103, "consisting essentially of" will be construed as equivalent to "comprising." Accordingly, the limitations of claim 43 have been addressed when addressing the limitations of claims 30 and 32 as discussed previously. Therefore, claim 43 is rejected based on the same reasons set forth previously in rejecting claims 30 and 32.
Regarding claim 44, as discussed above, Schenk discloses wherein adjuvants may be administered separately, before, concurrently with, or after administration of the therapeutic agent. Accordingly, it would have been obvious to one of ordinary skill in the art to have administered the alum (e.g., Alhydrogel®) separately, i.e., without a second active pharmaceutical ingredient.
Regarding claim 45, as discussed above, Schenk discloses treating or preventing Alzheimer’s Disease, which is characterized by beta-amyloid deposits. Similarly, as noted by p. 1, ¶ 2 of the instant Specification, Alzheimer’s disease is a type of dementia associated with amyloid deposition; as noted by p. 1, ¶ 3 of the Specification, Alzheimer’s disease is the most prominent form of beta-amyloidoses, characterized by beta-amyloid deposition.
Regarding claim 46, as discussed above, Schenk discloses wherein the formula comprises peptide in PBS added to Alhydrogel®.
Response to Arguments
Applicants mainly assert that Schenk discloses adjuvants, such as alum, can be used to enhance the immune response of the active ingredient, and whether it means that alum is used as an adjuvant for the polypeptides used as an AD vaccine in Schenk, or that it is made obvious to use alum as an effective ingredient specific for the treatment of AD, it cannot make the present invention – the use of alum as an effective ingredient for the treatment of AD – obvious. Alum is not even mentioned in the claims of Schenk (although cited throughout the text), thus Schenk does not teach or make it obvious that aluminum oxyhydroxide – by itself – is an effective ingredient in the treatment of AD, as convincingly shown by the data in the example section of the present application.
The Examiner appreciates Applicant’s explanation but does not find the assertions to be persuasive in view of the claims as amended. Amended instant claim 22 does not require aluminum oxyhydroxide by itself as an effective ingredient. For clarification, under the broadest reasonable interpretation the Examiner has interpreted amended claim 22 as a method comprising administering to a patient having a dementia associated with beta-amyloid deposition, a formulation comprising aluminum oxyhydroxide as an ingredient exerting an effect in an amount of at least about 1.2 mg. As such, the alum of Schenk, exerting an effect as an effective enhancer suitable in the treatment of AD, a progressive disease that results in dementia, reasonably appears to meet the limitations as instantly claimed. Moreover, regarding claim 44 and Applicant’s assertion of aluminum oxyhydroxide by itself, as discussed in the previous rejections, Schenk discloses wherein the adjuvants may be administered separately, before, concurrently with, or after administration of the therapeutic agent. Therefore, Schenk teaches or at least suggests administering alum (i.e. aluminum oxyhydroxide) separately (i.e. by itself) to exert an effect in a treatment regimen for a patient having a dementia associated with beta-amyloid deposition (i.e. progressed AD). As such, Applicant’s assertion is unpersuasive.
Regarding Applicant’s assertions about the probative value of the potential evidence of unexpected results in the example section of the present application, Applicant has the burden of explaining the data in any declaration they proffer as evidence of non-obviousness. MPEP § 716.02(b)(II). Note that factually uncorroborated assertions (such as those referenced in the specification) cannot take the place of evidence in the record. See MPEP § 716.01 (c)(Il). Moreover, any differences between the claimed invention and the prior art may be expected to result in some difference in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. The burden is on Applicant to establish that the results are in fact really unexpected and of statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318 (Bd. Pat. App. & Inter. 1992). See also MPEP § 716.02. In this instant case, Applicant does not appear to have discussed, in specific detail, with respect to the putative probative value of the objective data in the working examples.
Subsequently, assuming purely arguendo that the unexpectedness of the results has been established, the probative value of the evidence as compared to the invention as claimed must then be determined, i.e., the claims must be “commensurate in scope” with the showing. MPEP § 716.02(d). See also MPEP § 2145. Applicant must explain the “manner in which the specific compositions illustrated are considered to be commensurate in scope with the claimed invention”; see Ex parte Gelles, 22 USPQ2d 1318 (Bd. Pat. App. & Inter. 1992); see also MPEP 716.02, citing same. For example, it is noted that the examples compare results of 1mg and 2mg of aluminum oxyhydroxide administered subcutaneously. Specifically, Figs. 1 and 3 discuss the superior clinical effects of administering specifically 2mg of aluminum oxyhydroxide in comparison to 1mg in relation to disease progression. Similarly, p. 24, ¶ 2 of the instant Specification also notes where, over a treatment period of about one year, a clinical effect in AD treatment can be observed by measuring reduction in cognitive and/or functional decline by at least 30% compared to a normal development of decline in AD patients; where the intended patients would have a MMSE score of 23 or higher; and specifically, toward the bottom of p. 24 of the Specification, having a composite score change during treatment that remain essentially unchanged (i.e. still around the initial score) after 18 months. The Examiner notes the instant claims are not so limited. Applicant would need to explain how the specific subcutaneous administration amount of 2mg; the prerequisite MMSE score range of 23 or higher; and having a composite score change of less than 2 after 18 months of treatment are “reasonably representative” of the more broadly claimed subject matter of the claims, even were the results persuasively demonstrated to be “in fact really unexpected and of statistical and practical significance”.
Claims 39 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over US 2004/0219146 A1 (Schenk, 11/04/2004) in view of “How to administer a subcutaneous injection (Rushing, 06/2004).
The disclosures of Schenk is discussed above. While Schenk is believed to support a finding of obviousness, purely arguendo, for the purposes of complete prosecution, and for the purposes of this ground of rejection only, Schenk will be interpreted as though it does not explicitly disclose a location for subcutaneous administration.
However, Rushing discloses appropriate injection sites for subcutaneous injections include the outer aspect of the upper arm (¶ 4). Administration may be done by determining an appropriate needle size and angle (¶ 5, Fig. 2 on left).
Accordingly, it would have been obvious to one of ordinary skill in the art to have administered the dosage of Schenk in the upper arm, since it is a known and effective location suitable for subcutaneous delivery as taught by Rushing.
Similarly, regarding claim 41, Schenk will be interpreted as though it does not explicitly disclose utilizing a specific device for administering the subcutaneous dosages.
However, as discussed above, Rushing discloses administering subcutaneous injections with a syringe and needle (i.e. claimed injection device). Accordingly, it would have been obvious to one of ordinary skill in the art to have utilized an injection device such as a syringe and needle, to administer the dosage of Schenk, since it is a known and effective device for delivering subcutaneous injections as taught by Rushing.
Response to Arguments
Applicant does not present specific arguments with regards to Schenk and Rushing.
Since the Examiner has discussed Schenk above, this rejection is maintained.
Terminal Disclaimer
The terminal disclaimer filed on 17 September 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent Nos. 11,857,568, 11,147,873, 10,646,565, 10,478,454, and 11,065,273 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUCY TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Thursday 8:30 AM - 6:30 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SAHANA KAUP can be reached on (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
