Inguran, LLC - [2015] APO 64

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Inguran, LLC [2015] APO 64

Patent Application: 2013202635

Title:Apparatus and methods for high throughput sperm sorting

Patent Applicant:                   Inguran, LLC
Delegate:  Xavier Gisz
Decision Date:  30 September 2015
Hearing Date:  9 September 2015

Catchwords: PATENTS - examiner objection – inventive step – claim 1 contains a feature not disclosed in the prior art document – this feature provides an inventive step over the prior art – the claims are found inventive

Representation: Patent applicant: Andrew Fox of counsel for AJ Park

IP AUSTRALIA
AUSTRALIAN PATENT OFFICE
Patent Application: 2013202635

Title:Apparatus and methods for high throughput sperm sorting

Patent Applicant: Inguran, LLC
Date of Decision: 30 September 2015
DECISION
The claims as proposed to be amended in the letter of 9 July 2015 are considered inventive in light of US 2012/0202237 A1 (SEDOGLAVICH et al) when read in light of common general knowledge.
There is currently a postponement of acceptance in place on this application. This is the only impediment to the application being accepted. If the postponement of acceptance is withdrawn before the final acceptance date of 10 October 2015 then the application will be accepted.
REASONS FOR DECISION
Background

Patent application number 2013202635 (the Application) is a convention application filed on 5 April 2013 by Inguran, LLC (the Applicant). The Application claims priority from US13/830,316, US13/830,365, US13/830,333 and PCT/US2013/031706, all filed on 14 March 2013.
The Application has been the subject of six examination reports. The outstanding objections raised by the examiner relate only to the question of whether the alleged invention involves an inventive step.
The matter was heard in Canberra on 9 September 2015.
The application
In general terms, the Application relates to a microfluidic chip which allows the sorting of sperm by illuminating the sperm with light, measuring forward and side light emissions (fluorescence), and diverting the sperm according to the light emissions.
The claims
The specification as most recently proposed to be amended on 9 July 2015 ends with 19 claims; 1 independent claim and 18 appended claims. Claim 1 is reproduced below:
1. A method of sorting sperm comprising the steps of:
flowing sperm through a plurality of flow channels in a microfluidic chip;
orienting sperm within the plurality of flow channels flowing the oriented sperm through an inspection region in each of the flow channels;
interrogating sperm at the inspection region to determine sperm characteristics, wherein interrogated sperm emit a forward fluorescence in a forward direction and emit a side fluorescence in a direction perpendicular to the forward direction;
generating a first signal with a forward fluorescence detector in response to emitted electromagnetic radiation of sperm at the inspection region in the forward direction;
reflecting at least a portion of the emitted side fluorescence in a direction parallel with the forward fluorescence with a reflective element associated with each flow channel, wherein the reflective element is embedded within the microfluidic chip;
generating a second signal with a side fluorescence detector in response to the reflected side fluorescence;
differentiating oriented sperm from unoriented sperm in the flow channels;
selecting a subpopulation of oriented sperm based on the detected sperm characteristics; and
collecting the selected subpopulation of sperm in a collection vessel.
Relevant principles
As the Applicant requested examination before 15 April 2013, substantive amendments of the Patents Act 1990 (Cth) brought about by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012 (Cth) do not apply to the present consideration.
The objections of novelty, inventive step and innovative step are raised, and maintained, on the balance of probabilities. The balance of probabilities threshold was introduced into the Patents Act in 2001 by the Patents Amendment Act 2001 (Cth) (see Explanatory Memorandum, Patents Amendment Bill 2001 (Cth)).
The balance of probabilities requires examiners to weigh up all the material before them and decide, on balance, whether an objection is more likely than not to be applicable. Another way of viewing the balance of probabilities is that the objection is highly plausible, more probable than not or prima facie reasonable.
Examiner’s objection
Six adverse examination reports were issued on this application.
A first examination report issued on 10 January 2014 which found claims 1-14 to lack novelty and 15-18 to lack an inventive step in light of D1 – US 2012/0202237 A1 (SEDOGLAVICH et al.).
In response to the examiner’s first report the applicant proposed amendments on 20 August 2014 that added to claim 1 the features of detecting forward and side fluorescence.
A second examination report issued on 17 September 2014 which found that the invention defined in claims 1-13 of the proposed amendments lacked novelty, and claims 14-17 lacked inventive step in light of D1.
In response to the examiner’s second report the applicant proposed amendments on 12 January 2015 that added to claim 1 the feature of mirrors embedded in the microfluidic chip such that the side fluorescence was reflected in a direction parallel with the forward fluorescence.
A third examination report issued on 11 February 2015 which found that claims 1-16 and 18 lacked an inventive step in light of D1.
In response to the third report the applicant argued on 10 March 2015 that the claims were inventive and requested the examiner withdraw the inventive step objection.
A fourth examination report issued on 10 April 2015 in which the examiner maintained and further explained the inventive step objection.
In response to the fourth report, the applicant proposed amendments on 7 May 2015 adding the feature of a flow channel with a transition to a reduced flow height for orienting the sperm.
A fifth examination report was issued on 21 May 2015 maintaining the inventive step objection, noting that a flow channel with a transition to a reduced flow height for orienting the sperm was disclosed in D1.
In response to the fifth report, the applicant proposed amendments on 9 July 2015 that removed the previously added feature of a flow channel with a transition to a reduced height for orienting the sperm. In the response the applicant requested to be heard if the examiner intended to maintain the objection.
A sixth examination report was issued on 10 August 2015 maintaining the inventive step objection to claims 1-16 and 18. The sixth examination report included five prior art documents (D4-D8) which the examiner used to demonstrate that embedding mirrors in a microfluidic device was common general knowledge.
Publication details of documents D4-D8 details are provided below:
D4 - US 2008/0085552 A1 (LARSON et al.) 10 April 2008
D5 - US 2009/0051901 A1 (SHEN et al.) 26 February 2009
D6 - US 2009/0165876 A1 (ATKIN et al.) 02 July 2009
D7 - US 6,490,034 B1 (WOIAS et al.) 03 December 2002
D8 - US 7,906,321 B2 (MASTROMATTEO et al.) 15 March 2011
The examiner’s objection is reproduced below:
“The examiner has considered the arguments put forth by the applicant as filed on the 09 July 2015. However, the examiner is not convinced by the argument and therefore maintains the inventive step objection.
Argument Presented by the Applicant:
1) The examiner fails to appreciate the previously unrecognised technical advantage in embedding reflectors with each flow channel.
The examiner disagrees with the applicant, as seen in D4-D8 (evidence which show embedding reflectors in a microfluidics substrate) embedding a reflector in a microfluidics substrate is a common solution and would have formed the common general knowledge of the person skilled in the art. D4, figure 7 discloses a concave reflector which directs the light generated in the channel towards a detector. D5, figure 1; D6, figure 37; D7, figure 1 and D8, figure 9 discloses embedded reflectors which direct the incoming light across the fluidics channel then reflect the light beam to a detector. Therefore, the examiner is not convinced that having an embedded reflector will have an unexpected nor surprising results as it forms the common general knowledge of a person skilled in the art of microfluidics.
2) The previously undisclosed configuration provides a technical advantage over the prior art.
The examiner disagrees, as stated above the embedding of reflectors is a common solution and therefore, the examiner considers that the embedding of a reflector in the substrate of a microfluidics cell is merely a design choice.”
The examiner also made the flowing note in the report:
“The applicant requested a hearing if the examiner maintained the inventive step objection. Although I have maintained my inventive step objection, I have included reference to prior art documents not previously considered, and consequently believe that a hearing could be avoided in light of the updated inventive step objection.
If the applicant is still of the view that a hearing is necessary then a hearing can be set. I note that there is little time remaining for a hearing to take place and for a decision to issue before the final date for acceptance (10 October 2015). If a hearing were to take place within less than a month from the final date of acceptance it is unlikely that a decision would be issued before the final date of acceptance, and the applicant should consider filing a divisional application to retain the benefit of the earliest priority date.”
The applicant confirmed that they still wanted to be heard after receiving this report. The matter was heard on 9 September 2015.
Inventive step
Subsection 7(2) of the Act states that an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art in the light of the common general knowledge, considered alone or together with the prior art. A document is prior art for this purpose if "a skilled person mentioned in subsection (2) could, before the priority date of the relevant claim, be reasonably expected to have ascertained, understood, regarded [the document] as relevant" (s 7(3)).
The test for whether an invention is obvious is whether it would have been a matter of routine to proceed to the claimed invention. In Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd [1981] HCA 12 at [45], 148 CLR 262 at 286 Aickin J stated:
"The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not."
The High Court in Aktiebolaget Hässle v Alphapharm Pty Ltd (‘Alphapharm’) [2002] HCA 59 at [51]- [53]; [2002] HCA 59; 212 CLR 411 at [51]- [53] approved this approach, in addition to that taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at 187 in which Graham J had posed the question:
“Would the notional research group at the relevant date in all the circumstances directly be led as a matter of course to try [the claimed invention] in the expectation that it might well produce a useful [desired result]?”
The usual approach to determining inventive step is the problem-solution approach. Once the problem has been formulated and the common general knowledge and the prior art base has been determined, the question of whether the claimed solution is obvious must be addressed.
Where the claims are directed to a combination of features, the inquiry of inventive step is not whether the function performed by each individual feature is obvious, but whether the combination of features is obvious (Lockwood Security Products Pty Ltd v Doric Products Pty Ltd [2004] HCA 58 and Garford Pty Ltd v DYWIDAG Systems International Pty Ltd [2015] FCAFC 6).
Person skilled in the art
The person skilled in the art in this case is a person or team who, at the priority date, had expertise in cell separation and in particular sperm sorting. The person would have knowledge of flow cytometers and microfluidics.
The problem the invention overcomes
The background of the description notes that sperm sorting has largely relied on droplet flow cytometers which is damaging to sperm. I am satisfied that the problem to be overcome was for a sperm sorting method that was less damaging to sperm than existing methods.
Ascertained, Understood and Regarded as Relevant
As the person skilled in the art was in a technically sophisticated field, it is reasonable to expect that the person would review documents such as journals and patents for existing methods of sorting sperm. US patent application US 2012/0202237 A1 (SEDOGLAVICH et al) was published on 9 August 2012 and explicitly relates to sperm sorting, thus could be reasonably expected to have been ascertained, understood and regarded as relevant by a person skilled in the art at the priority date.
The invention disclosed in D1
D1 discloses an apparatus for sorting sperm using a flow cytometer. D1 also discloses at figure 3 and paragraph 46 the use of a microfluidic chip as an alternative to the flow cytometer. Eight of these features are disclosed in D1, while two features (features 1 and 6) are not explicitly disclosed in D1 as set out below:
1.flowing sperm through a single flow channel in a microfluidic chip (figure 3) (a plurality of flow channels is not disclosed)
2.orienting sperm within the plurality of flow channels (paragraph 29 describes orienting particles in a cytometer with a nozzle assembly (62) and orienting tip (124))
3.flowing the oriented sperm through an inspection region in each of the flow channels (the microfluidic chip has an inspection zone (16’))
4.interrogating sperm at the inspection region to determine sperm characteristics, wherein interrogated sperm emit a forward fluorescence in a forward direction and emit a side fluorescence in a direction perpendicular to the forward direction (paragraph 38)
5.generating a first signal with a forward fluorescence detector in response to emitted electromagnetic radiation of sperm at the inspection region in the forward direction (figure 2)
6.reflecting at least a portion of the emitted side fluorescence in a direction parallel with the forward fluorescence with a reflective element associated with each flow channel, wherein the reflective element is embedded within the microfluidic chip (not disclosed in D1);
7.generating a second signal with a side fluorescence detector in response to the reflected side fluorescence (figure 2)
8.differentiating oriented sperm from unoriented sperm in the flow channels (the separator (34’))
9.selecting a subpopulation of oriented sperm based on the detected sperm characteristics (paragraph 45)
10.collecting the selected subpopulation of sperm in a collection vessel (collection container 126’).
D1 does not disclose the features of a plurality of flow channels or reflective elements embedded in the microfluidic chip.
The Applicant argued that the disclosure at figure 3 and paragraph 46 was insufficient to allow a person skilled in the art to make the microfluidic embodiment of the invention. Specifically, the Applicant argued that the measurement system used in the flow cytometer could not be used with the microfluidic chip, without some inventiveness. The measurement system used in the flow cytometer is shown in Figure 2, which is reproduced below with item numbers removed for clarity:
Although the disclosure is brief, I consider that it would require only routine and non-inventive steps to make the microfluidic chip embodiment of the invention disclosed at figure 3 and paragraph 46. This would simply require substituting the fluid stream of the flow cytometer with a flow channel of a microfluidic chip. I have illustrated this below, wherein the incomplete rectangle surrounding the flow channel represents the microfluidic chip in cross-section:
Thus D1 discloses a microfluidic chip with a single flow channel. The placement of a plurality of flow channels on the microfluidic chip is discussed further below.
Obviousness
Would it be a matter of routine to use mirrors to redirect light?
Redirecting light with a mirror so as to allow the flexibility of placing the photodetector more conveniently is ubiquitous in the field of optics, thus this feature alone does not provide an inventive step.
Is embedding a mirror in the microfluidic chip common general knowledge?
In the examiner’s 6^th adverse report the examiner raised 5 documents (D4-D8) to establish that embedding mirrors into microfluidic chips is common general knowledge. On the basis of these documents I am satisfied that microfluidic chips with embedded mirrors were common general knowledge at the priority date.
Would it be a matter of routine to have a plurality of flow channels on the microfluidic chip?
D1 discloses a microfluidic chip with a single flow channel. Using a plurality of flow channels on the micro-fluidic chip (with each channel having associated orienters, detectors and sorters) would increase the rate at which sperm could be sorted. I consider that the general concept of having a plurality of flow channels on a microfluidic chip is common general knowledge.
One obvious modification to D1 would be the inclusion of a plurality of flow channels wherein each flow channel is adjacent an edge or different edges of a microfluidic chip, with sensors placed at the edge(s) and on one side of the microfluidic chip. It would not be a matter of routine to place a plurality of flow channels in any other configuration on the microfluidic chip of D1 (for example a plurality of flow channels in parallel) because optical paths to at least one of the three sides to one flow channel would be obstructed by adjacent flow channels.
Would it be a matter of routine to use embedded mirrors to make side fluorescence parallel with forward fluorescence?
The purpose of embedded mirrors in the common general knowledge is to allow the light to enter the microfluidic chip, pass through the fluid being analysed, and reflect the light back out of the chip. The documents D4-D8 disclose microfluidic chips with embedded mirrors but these microfluidic chips serve different purposes than the presently claimed invention. The closest of these documents to the claimed invention is D5 – US 2009/0051901 A1 (Shen et al), which discloses an analogous but inverted configuration claimed in the present invention; it allows for side fluorescence to be detected directly (as seen in figure 1 item 120, and paragraph 46), while the forwardly directed light is reflected and then detected.
I consider that using mirrors embedded in the microfluidic chip, though common general knowledge, is inventive in this case because it is done to achieve a different effect than that of the common general knowledge – to redirect side fluorescence to be parallel with forward fluorescence. The embedded mirrors enable a plurality of flow channels to be placed on the microfluidic chip in configurations not otherwise possible (including the preferred embodiment of a plurality of flow channels in a parallel configuration). Redirecting the light with the embedded mirrors also allows for detection on a coplanar array of detectors which results in the advantages of a potentially more compact, and thus cheaper and simpler, device. These advantages provided by the embedded mirrors are at least neutral to, and arguably supportive of, the conclusion that this feature is inventive.
Obviousness summary
The claimed invention contains a feature that would not be considered a matter of routine to a person skilled in the art: embedding reflective elements in the microfluidic chip to reflect side fluorescent light to be parallel with forward fluorescent light. Consequently I consider the invention defined in claim 1 (and all claims appended thereon) to be inventive in light of D1 and common general knowledge.
Contrast between the decision and the Examiner’s objection

This decision has reached a different conclusion on inventive step than the examination reports which is briefly discussed as follows. The examiner focused the question of inventive step narrowly as to whether embedding mirrors in microfluidic chips is common general knowledge. Although this is a relevant question and indeed a question to which I came to the same conclusion as the examiner, it is only one aspect of the entire consideration of inventive step. In contrast to the examiner’s approach, the analysis in this decision is less narrowly focused by considering the combination of features as a whole and has addressed pertinent questions such as how the microfluidic embodiment disclosed in D1 would actually operate and what non-inventive variations a person skilled in the art (without the benefit of hindsight) could be expected to make to D1.
Conclusion
The claims as proposed to be amended in the letter of 9 July 2015 are considered inventive in light of US 2012/0202237 A1 (SEDOGLAVICH et al) when read in light of common general knowledge.
There is currently a postponement of acceptance in place on this application. This is the only impediment to the application being accepted. If the postponement of acceptance is withdrawn before the final acceptance date of 10 October 2015 then the application will be accepted.
Xavier Gisz
Delegate of the Commissioner of Patents