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 .
Detailed Action
The Amendments and Remarks filed 8/13/26 in response to the Office Action of 2/13/26 are acknowledged and have been entered.
Claim 46 has been added by Applicant.
Claims 2, 4, 5, 7-13, 35, 37, and 43-46 are pending.
Claims 2, 9, 10, 35, and 37 have been amended by Applicant.
Claims 2, 4, 5, 7-13, 35, 37, and 43-46 are currently under examination.
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 following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn.
The rejections of claims 10, 35, and 37 under 35 U.S.C. 103 are withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claim(s) 2, 4, 5, 7-9, 12, 43, and 45 remain rejected and claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Schwabe et al (WO 2017/062672 A2; 4/13/17; 11/6/24 IDS) in view of Wong et al (Alzheimer’s & Dementia, 1027, 810-827), Gong et al (Journal of Histochemistry & Cytochemistry, 2013, 6(12): 857-868), Guerreiro et al (NEJM, 2013, 368(2): 117-127), Cantoni et al (Acta Neuropathol, 2015, 129: 429-447), and Kersten (Biochimica et Biophysica, 2014, 1841: 919-933).
Schwab et al teaches TREM2 is expressed on myeloid cells ([0004], in particular). Schwabe et al teaches a method of treating Alzheimer’s disease (AD) in a mammal subject comprising administering to the mammal subject an effective amount of agonist anti-TREM2 antibody 7E5 (see Example 16, Fig. 8A, and Fig. 9A, in particular). Example 16 of Schwabe et al teaches, in mouse models of AD, anti-TREM2 antibody 7E5 has been shown to: (i) modulate inflammatory signaling by decreasing level of CD11c and increasing levels of Fabp3, CCL2, CXCL10, Rorc, Fab5, and TNFa; (ii) improve special learning and memory defects; and (iii) improve cognitive learning. Schwab et al further teaches the agonist anti-TREM2 antibody has been shown to reduce inflammation ([0682], in particular).
Schwabe et al does not specifically teach the mammal subject with AD has dysregulated lipid metabolism and/or increased accumulation of one or more lipids, such as triacylglycerides or cholesterol esters. However, these deficiencies are made up in the teachings of Wong et al, Gong et al, Guerreiro et al, Cantoni et al, Kersten.
At the right column on page 811, Wong et al teaches: “There is a strong body of evidence from both animal models and studies in humans that associate abnormal lipid metabolism with AD (Fig. 1). The main classes known to be disrupted in AD include cholesterol, sphingolipids, phospholipids, and glycerolipids including gangliosides.” Wong further teaches a 40% reduction in sulfatide (recited by instant claim 7) correlating with clinical dementia and a sulfatide/PI ratio correlating with incident AD (Table 1, in particular). Wong further teaches the ganglioside (recited by instant claim 11) GAb as a being found in human brain during AD and suggests GAb as an important biomarker for early detection of AD pathology (page 814, in particular).
Gong et al teaches lipoprotein lipase (LPL) is known to be responsible for hydrolyzing lipids (left column on page 858, in particular) and exhibits markedly reduced levels in the dentate gyrus of AD brains (Abstract, in particular).
Guerreiro et al teaches the presence of T66M TREM2 loss-of-function variants in patients with AD (right column on page 120, in particular).
Cantoni et al teaches loss of TREM2 results in microglia (a type of myeloid cell) with defects in lipid metabolism, a decrease in lipoprotein lipase (LPL), and defective myelin (which is known in the prior art as a lipid sheath) degradation (page 441, in particular). Cantoni et al further teaches the loss of TREM2 results in decreases in LPL at both transcriptional and translational levels (first full paragraph at right column on page 441, in particular).
The Abstract of Kersten teaches LPL, which is taught by Cantoni et al to be decreased in microglia with reduced TREM2, hydrolyzes triacylglyceride (same as “triglyceride”). Using a mouse model overexpressing LPL, Kersten further teaches elevated expression of LPL results in reduction in triacylglyceride (right column on page 919, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, perform the method of Schwabe et al to treat the just any subject with AD (including a human subject with AD) with reduced TREM2 activity by administering an agonist anti-TREM2 antibody because the method of Schwabe et al is taught to provide therapeutic benefit to subjects with AD by administering an agonist of TREM2. Such subjects include: subjects with AD having just any cells exhibiting abnormal lipid metabolism described by Wong et al and/or accumulation of just any lipid; subjects with abnormal deposits of cholesterol esters described by Lobanova et al; and mammalian subjects with reduced TREM2 activity, such as a subject with AD found to have a T66M TREM2 loss-of-function mutation taught by Guerreiro et al exhibits reduced TREM2 activity, that would predictably result in the subject having microglia with defects in lipid metabolism because Cantoni et al teaches loss of TREM2 results in microglia with defects in lipid metabolism, defects in myelin degradation, and reduction in LPL (Cantoni et al teaches the loss of TREM2 results in decreases in LPL at both transcriptional and translational levels) - which would predictably result in accumulation of lipids such as triacylglyceride due to loss of LPL hydrolysis of triacylglyceride as a result in LPL decrease because Kersten teaches LPL hydrolyzes triglycerides and Kersten teaches (in a transgenic mouse model) expression level of LPL (which hydrolyzes triacylglyceride) inversely correlating with levels of triacylglyceride (right column on page 919, in particular).
Reduction in lipid accumulation would predictably occur when performing the combined method with an AD subject found to have reduced TREM2 activity because the administered TREM2 agonist would predictably reverse lipid accumulation due to low TREM2 activity. Further, while the cited references do not demonstrate the combined method results in reduced expression of pro-inflammatory cytokines recited by instant claim 12, the method appears to be the same absent a showing otherwise.
Further, the examiner takes the positions that reduction of expression of pro-inflammatory cytokines recited by instant claim 12 is not a property having significance greater than that of the expected property of a predicted therapeutic effect of treating AD taught by the cited references. Therefore, recitation that the combined method has the property of being able to reduce expression of pro-inflammatory cytokines recited by instant claim 12 is not sufficient to rebut obviousness of the combined method when combined method is expected to have the equal or greater property of expected therapeutic benefit. See MPEP 716.02(c). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results. Further, see In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991), where the court held that the fact that another advantage would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 8/13/26, Applicant argues Cantoni et al fails to establish that a lack of TREM2 results in dysregulated lipid metabolism or increased accumulation of cholesteryl esters or triacylglycerides. Applicant further argues Cantoni does not demonstrate that an agonist anti-TREM2 antibody can treat accumulation of cholesteryl esters or triacylglycerides. Applicant further argues Cantoni does not show any data supporting an impact on LPL activity or an accumulation of triacylglyceride as a result of recued LPL expression levels. Applicant further argues the rejection is based on impermissible hindsight and the examiner has failed to establish that one skilled in the art would have had the motivation to practice the claimed method or would have had a reasonable expectation that reduced LPL expression observed by Cantoni et al would have resulted in cholesteryl ester/triacylglyceride accumulation or that the administration of an agonist anti-TREM2 antibody would have treated such increased accumulation. Applicant further argues cited references do not specifically discuss treating dysregulated lipid metabolism comprising increased accumulation of cholesteryl esters, triacylglycerides, or combinations thereof in a mammal in need thereof with an agonist anti-TERM2 antibody and cited documents do not provide motivation to treat the recited population with an agonist anti-TREM2 antibody or a reasonable expectation of success. Applicant further cites post-filing teachings of Malliou et al (Mol Neuro Adv, 2026, 3(1):11) as teaching Alzheimer’s disease (AD) patients include those with reduced (as opposed to increased) lipid levels and Schwab et al does not specifically discuss treating dysregulated lipid metabolism characterized by increased accumulation of cholesteryl esters or triacylglycerides in AD patients.
The amendments to the claims and the arguments found in the Reply of 8/13/26 have been carefully considered, but are not deemed persuasive. In regard to the arguments that Cantoni et al fails to establish that a lack of TREM2 results in dysregulated lipid metabolism or increased accumulation of cholesteryl esters or triacylglycerides and Cantoni does not show any data supporting an impact on LPL activity or an accumulation of triacylglyceride as a result of recued LPL expression levels, 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). Cantoni et al teaches a lack of TREM2 results in microglia (a type of myeloid cell) with defects in lipid metabolism, a decrease in lipoprotein lipase (LPL), and defective myelin (which is known in the prior art as a lipid sheath) degradation (page 441, in particular). Cantoni et al further teaches the loss of TREM2 results in decreases in LPL at both transcriptional and translational levels (first full paragraph at right column on page 441, in particular). Such a loss in TREM2, resulting in a decrease in LPL, would predictably result in accumulation of lipids such as triacylglyceride due to loss of LPL hydrolysis of triacylglyceride as a result in LPL decrease because Kersten teaches LPL hydrolyzes triglycerides and Kersten teaches (in a transgenic mouse model) expression level of LPL (which hydrolyzes triacylglyceride) inversely correlating with levels of triacylglyceride (right column on page 919, in particular)
In regards to the argument that Cantoni does not demonstrate that an agonist anti-TREM2 antibody can treat accumulation of cholesteryl esters or triacylglycerides, 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). However, reduction in lipid accumulation would predictably occur when performing the combined method with an AD subject found to have reduced TREM2 activity because the administered TREM2 agonist would predictably reverse lipid accumulation due to low TREM2 activity.
In regard to the arguments the rejection is based on impermissible hindsight, the examiner has failed to establish that one skilled in the art would have had the motivation to practice the claimed method or would have had a reasonable expectation that reduced LPL expression observed by Cantoni et al would have resulted in cholesteryl ester/triacylglyceride accumulation or that the administration of an agonist anti-TREM2 antibody would have treated such increased accumulation, that cited references do not specifically discuss treating dysregulated lipid metabolism comprising increased accumulation of cholesteryl esters, triacylglycerides, or combinations thereof in a mammal in need thereof with an agonist anti-TERM2 antibody, and cited documents do not provide motivation to treat the recited population with an agonist anti-TREM2 antibody or a reasonable expectation of success: it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Again, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, perform the method of Schwabe et al to treat the just any subject with AD (including a human subject with AD) with reduced TREM2 activity by administering an agonist anti-TREM2 antibody because the method of Schwabe et al is taught to provide therapeutic benefit to subjects with AD by administering an agonist of TREM2. Such subjects include: subjects with AD having just any cells exhibiting abnormal lipid metabolism described by Wong et al and/or accumulation of just any lipid; subjects with abnormal deposits of cholesterol esters described by Lobanova et al; and mammalian subjects with reduced TREM2 activity, such as a subject with AD found to have a T66M TREM2 loss-of-function mutation taught by Guerreiro et al exhibits reduced TREM2 activity, that would predictably result in the subject having microglia with defects in lipid metabolism because Cantoni et al teaches loss of TREM2 results in microglia with defects in lipid metabolism, defects in myelin degradation, and reduction in LPL (Cantoni et al teaches the loss of TREM2 results in decreases in LPL at both transcriptional and translational levels) - which would predictably result in accumulation of lipids such as triacylglyceride due to loss of LPL hydrolysis of triacylglyceride as a result in LPL decrease because Kersten teaches LPL hydrolyzes triglycerides and Kersten teaches (in a transgenic mouse model) expression level of LPL (which hydrolyzes triacylglyceride) inversely correlating with levels of triacylglyceride (right column on page 919, in particular). Reduction in lipid accumulation would predictably occur when performing the combined method with an AD subject found to have reduced TREM2 activity because the administered TREM2 agonist would predictably reverse lipid accumulation due to low TREM2 activity.
In regards to the citation of post-filing teachings of Malliou et al (Mol Neuro Adv, 2026, 3(1):11) as teaching Alzheimer’s disease (AD) patients include those with reduced (as opposed to increased) lipid levels, the examiner acknowledges that AD patients include those with reduced lipid levels and those with increased lipid levels.
In regards to the argument Schwab et al does not specifically discuss treating dysregulated lipid metabolism characterized by increased accumulation of cholesteryl esters or triacylglycerides in AD patients, 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).
Claim Rejections - 35 USC § 103
Claim(s) 2, 4, 5, 7-9, 12, 13, 43, and 45 remain rejected and claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Schwabe et al (WO 2017/062672 A2; 4/13/17; 11/6/24 IDS) in view of Wong et al (Alzheimer’s & Dementia, 1027, 810-827), Gong et al (Journal of Histochemistry & Cytochemistry, 2013, 6(12): 857-868), Guerreiro et al (NEJM, 2013, 368(2): 117-127), Cantoni et al (Acta Neuropathol, 2015, 129: 429-447), and Kersten (Biochimica et Biophysica, 2014, 1841: 919-933) as applied to claims 2, 4, 5, 7-9, 12, 43, 45, and 46 above, and further in view of Crunkhorn (Nature Reviews Drug Discovery, 2012, 11(271)).
Teachings of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten are discussed above.
Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten do not teach administering an RXR agonist. However, these deficiencies are made up in the teachings of Crunkhorn.
Crunkhorn teaches administering an RXR agonist reverses AD (see title and entire article, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating AD of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten wherein the subject with AD is further administered an RXR agonist in an effort to obtain further therapeutic benefit for the subject with AD because Crunkhorn teaches administering an RXR agonist reverses AD. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 8/13/26, Applicant repeats arguments addressed above.
Claim Rejections - 35 USC § 103
Claim(s) 2, 4, 5, 7-9, 12, and 43-45 remain rejected and claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Schwabe et al (WO 2017/062672 A2; 4/13/17; 11/6/24 IDS) in view of Wong et al (Alzheimer’s & Dementia, 1027, 810-827), Gong et al (Journal of Histochemistry & Cytochemistry, 2013, 6(12): 857-868), Guerreiro et al (NEJM, 2013, 368(2): 117-127), Cantoni et al (Acta Neuropathol, 2015, 129: 429-447), and Kersten (Biochimica et Biophysica, 2014, 1841: 919-933) as applied to claims 2, 4, 5, 7-9, 12, 43, 45, and 46 above, and further in view of Saher et al (Biochimica et Biophysica Acta, 2015, 1851: 1083-1094).
Teachings of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten are discussed above.
Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten do not specifically teach the accumulated lipids of the microglia of the combined method include free cholesterol. However, these deficiencies are made up in the teachings of Saher et al.
Saher et al teaches the largest pool of free cholesterol in mammals resides in myelin membranes (Abstract, in particular), which are taught by Cantoni et al to exhibit defective degradation with reduced TREM2.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating AD of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten wherein the lipid accumulation due to microglia cells of the combined method exhibiting TREM2 loss or deficiency includes free cholesterol because Cantoni et al teaches reduced TREM2 results in defective degradation of myelin membranes – the location of the largest pool of free cholesterol in mammals. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 8/13/26, Applicant repeats arguments addressed above.
Claim Rejections - 35 USC § 103
Claim(s) 2, 4, 5, 7-9, 12, 43, and 45 remain rejected and claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Schwabe et al (WO 2017/062672 A2; 4/13/17; 11/6/24 IDS) in view of Wong et al (Alzheimer’s & Dementia, 1027, 810-827), Lobanova et al (arXiv, 2018, 1803.01201, 11 pages), Gong et al (Journal of Histochemistry & Cytochemistry, 2013, 6(12): 857-868), Guerreiro et al (NEJM, 2013, 368(2): 117-127), Cantoni et al (Acta Neuropathol, 2015, 129: 429-447), and Kersten (Biochimica et Biophysica, 2014, 1841: 919-933).
Schwab et al teaches TREM is expressed on myeloid cells ([0004], in particular). Schwabe et al teaches a method of treating Alzheimer’s disease (AD) in a mammal subject comprising administering to the mammal subject an effective amount of agonist anti-TREM2 antibody 7E5 (see Example 16, Fig. 8A, and Fig. 9A, in particular). Example 16 of Schwabe et al teaches, in mouse models of AD, anti-TREM2 antibody 7E5 has been shown to: (i) modulate inflammatory signaling by decreasing level of CD11c and increasing levels of Fabp3, CCL2, CXCL10, Rorc, Fab5, and TNFa; (ii) improve special learning and memory defects; and (iii) improve cognitive learning. Schwab et al further teaches the agonist anti-TREM2 antibody has been shown to reduce inflammation ([0682], in particular).
Schwabe et al does not specifically teach the mammal subject with AD has dysregulated lipid metabolism and/or increased accumulation of one or more lipids, such as triacylglycerides or cholesterol esters. However, these deficiencies are made up in the teachings of Wong et al, Lobanova et al, Gong et al, Guerreiro et al, Cantoni et al, Kersten.
At the right column on page 811, Wong et al teaches: “There is a strong body of evidence from both animal models and studies in humans that associate abnormal lipid metabolism with AD (Fig. 1). The main classes known to be disrupted in AD include cholesterol, sphingolipids, phospholipids, and glycerolipids including gangliosides.” Wong further teaches a 40% reduction in sulfatide (recited by instant claim 7) correlating with clinical dementia and a sulfatide/PI ratio correlating with incident AD (Table 1, in particular). Wong further teaches the ganglioside (recited by instant claim 11) GAb as a being found in human brain during AD and suggests GAb as an important biomarker for early detection of AD pathology (page 814, in particular).
Lobanova et al teaches abnormal deposits of cholesterol esters in amyloid-b plaques of AD human brains (Abstract, in particular).
Gong et al teaches lipoprotein lipase (LPL) is known to be responsible for hydrolyzing lipids (left column on page 858, in particular) and exhibits markedly reduced levels in the dentate gyrus of AD brains (Abstract, in particular).
Guerreiro et al teaches the presence of T66M TREM2 loss-of-function variants in patients with AD (right column on page 120, in particular).
Cantoni et al teaches loss of TREM2 results in microglia with defects in lipid metabolism, a decrease in lipoprotein lipase (LPL), and defective myelin (which is known in the prior art as a lipid sheath) degradation (page 441, in particular).
The Abstract of Kersten teaches LPL, which is taught by Cantoni et al to be decreased in microglia with reduced TREM2, hydrolyzes triacylglyceride (same as “triglyceride”). Using a mouse model overexpressing LPL, Kersten further teaches elevated expression of LPL results in reduction in triacylglyceride (right column on page 919, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, perform the method of Schwabe et al to treat the just any subject with AD by administering an agonist anti-TREM2 antibody because the method of Schwabe et al is taught to provide therapeutic benefit to subjects with AD by administering an agonist of TREM2. Such subjects include: subjects with AD having just any cells exhibiting abnormal lipid metabolism described by Wong et al and/or accumulation of just any lipid; subjects with abnormal deposits of cholesterol esters described by Lobanova et al; and mammalian (including human) subjects with reduced TREM2 activity, such as a subject with AD found to have a T66M TREM2 loss-of-function mutation taught by Guerreiro et al that exhibits reduced TREM2 activity, that would predictably result in the subject having microglia with defects in lipid metabolism because Cantoni et al teaches loss of TREM2 results in microglia with defects in lipid metabolism, defects in myelin degradation, and reduction in LPL – which would predictably result in accumulation of lipids such as triacylglyceride due to loss of LPL hydrolysis of triacylglyceride because Kersten teaches LPL hydrolyzes triglycerides and Kersten teaches (in a transgenic mouse model) expression level of LPL (which hydrolyzes triacylglyceride) inversely correlating with levels of triacylglyceride (right column on page 919, in particular).
Reduction in lipid accumulation would predictably occur when performing the combined method with AD subject found to have reduced TREM2 activity because the administered TREM2 agonist would predictably reverse lipid accumulation due to low TREM2 activity. Further, while the cited references do not demonstrate the combined method results in reduced expression of pro-inflammatory cytokines recited by instant claim 12, the method appears to be the same absent a showing otherwise.
Further, the examiner takes the positions that reduction of expression of pro-inflammatory cytokines recited by instant claim 12 is not a property having significance greater than that of the expected property of a predicted therapeutic effect of treating AD taught by the cited references. Therefore, recitation that the combined method has the property of being able to reduce expression of pro-inflammatory cytokines recited by instant claim 12 is not sufficient to rebut obviousness of the combined method when combined method is expected to have the equal or greater property of expected therapeutic benefit. See MPEP 716.02©. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results. Further, see In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991), where the court held that the fact that another advantage would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 8/13/26, Applicant repeats arguments addressed above.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 103
Claim(s) 10, 35, and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schwabe et al (WO 2017/062672 A2; 4/13/17; 11/6/24 IDS) in view of Wong et al (Alzheimer’s & Dementia, 1027, 810-827), Gong et al (Journal of Histochemistry & Cytochemistry, 2013, 6(12): 857-868), Guerreiro et al (NEJM, 2013, 368(2): 117-127), Cantoni et al (Acta Neuropathol, 2015, 129: 429-447), and Kersten (Biochimica et Biophysica, 2014, 1841: 919-933) as applied to claims 2, 4, 5, 7-9, 12, 43, and 45 above, and further in view of Ferreira et al (Alzheimer’s & Dementia, 2014, 10: S76-S83) and Breiner et al (Annu Rev Med, 1996, 47: 401-411).
Teachings of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten are discussed above.
Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten do not specifically teach AD subjects treated by the combined method have inflammation and/or rheumatoid arthritis. However, these deficiencies are made up in the teachings of Ferreira et al and Breiner et al.
Ferreira et al teaches inflammation plays critical roles in the pathogenesis of AD (paragraph spanning columns of page S76, in particular).
Breiner et al teaches evidence implicates inflammation in the pathogenesis of AD and anti-inflammatory treatments have been shown to prevent or ameliorate symptoms of AD (Abstract, in particular). Breiner et al further teaches subjects with AD can also have rheumatoid arthritis (page 403, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Schwabe et al, Wong et al, Gong et al, Guerreiro et al, Cantoni et al, and Kersten wherein the subjects treated for AD by the combined method also have inflammation and/or rheumatoid arthritis because the combined method therapeutic treats AD, an agonist anti-TREM2 antibody of the combined method has been shown to reduce inflammation ([0682], in particular), Ferreira et al teaches inflammation plays critical roles in the pathogenesis of AD (paragraph spanning columns of page S76, in particular), Breiner et al teaches evidence implicates inflammation in the pathogenesis of AD and anti-inflammatory treatments have been shown to prevent or ameliorate symptoms of AD (Abstract, in particular), and Breiner et al teaches subjects with AD that also have rheumatoid arthritis (page 403, in particular). Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm ET.
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, Samira Jean-Louis can be reached at (571)270-3503. 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.
/SEAN E AEDER/Primary Examiner, Art Unit 1642
Prosecution Insights